Articles tagged as "Key populations"

Health economics of PrEP in Europe

Editor’s notes: One of the most common questions for policy makers considering the introduction of PrEP is how much it will cost and whether the benefits will outweigh the costs.  The answers to these questions will be dependent on the specific context but will be strongly influenced by four factors: the cost of PrEP (including its delivery); the savings due to reduced costs of HIV care; the effectiveness of PrEP; and the incidence of HIV in the population who receive PrEP.  The effectiveness and the incidence can be combined to calculate the number needed to treat to prevent an HIV infection.  As mentioned above, both PROUD and Ipergay demonstrated excellent effectiveness in populations that were highly at risk, as shown by the very high incidence in the placebo or deferred arms of these studies.  Durand-Zaleski and colleagues present their analysis of the costs and benefits of PrEP as used in the Ipergay study.  Most participants were in France, where lifetime costs of HIV treatment are estimated to be more than 500 000 euros.  At the time of Ipergay, the medicines for PrEP cost more than 500 euros monthly, but subsequently generic medicines have become available in France for around 180 euros monthly, and the price in France is approximately US$60 per month from Indian suppliers over the internet. When other health related costs are included, the costs to prevent an HIV infection vary from 27 000 to 75 000 euros depending on the costs of the medicines.  The confidence intervals around these estimates are wide because the trial was stopped before there were too many infections given the clear evidence of efficacy.  This model does not discount future costs, as it uses a short time horizon.  The model also does not consider ongoing transmission, which the authors estimate to be around two to three additional people given data from Ipergay’s sexual mixing data.  So, the conclusions that the benefits of PrEP outweigh the costs are based on conservative assumptions for this population.  However, it is important to recognize that the study population had an HIV incidence of 6.6 per 100 person-years and the incidence was more than nine per 100 person-years in the participants recruited into the placebo arm in the two Paris sites.  This led to an estimated number needed to treat of around 18 overall and around 13 for the Parisian sites.  WHO recommends that PrEP is offered to all people at significant risk of HIV infection, in whom the incidence might be more than three per 100 person-years.  An incidence of 3% would more than double the costs per infection averted calculated in this study, and an incidence of 0.66% (which would still represent an important and ongoing HIV epidemic, such as that seen on average in recent PHIA studies in Zambia and twice that seen in Malawi) would increase the costs per infection averted by tenfold.  From a health economic perspective, PrEP should always be prioritized to people who are most at risk.  From a human rights perspective, PrEP should be offered to anyone who wants it and in whom the epidemiological and psychological benefits outweigh the very small clinical risks of taking tenofovir and emtricitabine.

Cambiano and colleagues have modelled the potential impact and costs of PrEP in the UK population of gay men and men who have sex with men.  They assumed that PrEP would be offered to HIV-negative men who reported condomless anal sex in the past three months. Over the next 80 years, HIV infections would be prevented both directly and because of ongoing transmission to other men, leading to considerable cost-savings in terms of health care costs.  Overall, the authors predict that such a PrEP programme might save one billion pounds and avert approximately 25% of the HIV infections that would have been seen in the absence of the programme.  The results included a wide range of probabilistic uncertainty sampling.  The largest changes to their estimates would come from reductions in the costs of ARVs (for both treatment and for PrEP).  If PrEP was considerably cheaper, the time to break even in costs terms would be shorter.  On the one hand, we need models with a long-time horizon to capture all the benefits of preventing HIV infection today.  On the other hand, changes in technologies that may arise in the future cannot be incorporated into such models despite our hope that HIV prevention and treatment is likely to be very different over the next decades.

Costs and benefits of on-demand HIV pre-exposure prophylaxis in MSM.

Durand-Zaleski I, Mutuon P, Charreau I, Tremblay C, Rojas D, Pialoux G, Chidiac C, Capitant C, Spire B, Cotte L, Chas J, Meyer L; Molina JM for the ANRS IPERGAY study group. AIDS. 32(1):95–102, 2018 Jan 2. doi:10.1097/QAD.0000000000001658. [Epub 2017 Oct 12]

Objectives: We undertook the economic evaluation of the double-blind randomized ANRS-IPERGAY trial, which showed the efficacy of on-demand preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) in preventing HIV infection among high-risk MSM.

Design and methods: The economic evaluation was prospective. Counseling, drugs (TDF-FTC at €500.88 for 30 tablets), tests, visits, and hospital admissions were valued based on in-trial use. The cost of on-demand PrEP/HIV infection averted was compared with the yearly and lifetime costs of HIV infection in France in a cost and benefits analysis.

Results: The yearly number of participants needed to treat to prevent one HIV infection was 17.6 (95% confidence interval = 10.7–49.9). The annual cost of counseling was €690/participant. The total 1-year costs of PrEP were €4271/participant, of which €3129 (73%) were drug costs corresponding to 15 tablets of TDF-FTC/month. The yearly cost of on-demand PrEP to avoid one infection was €75  258. Using TDF-FTC generic (€179.9/30 tablets) reduced the 1-year costs of on-demand PrEP to €2271/participant and €39  970/infection averted, respectively. Using TDF-FTC at international market discounted prices (€60/30 tablets) reduced the costs to €1517/participant and the cost to €26  787/infection averted, comparable with the yearly treatment cost of HIV infection in France. On-demand PrEP was found to be cost saving in France if the duration of exposure was less than 7.5 years at current drug price and 13 years at generic price.

Conclusion: On-demand PrEP in high-risk MSM with TDF-FTC can be considered cost saving. Other benefits include the treatments of other diseases and reductions in secondary infections.

Abstract access 

Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation.

Cambiano V, Miners A, Dunn D, McCormack S, Ong KJ, Gill ON, Nardone A, Desai M, Field N, Hart G, Delpech V, Cairns G, Rodger A, Phillips AN. Lancet Infect Dis. 2017 Oct 17. doi:10.1016/S1473-3099(17)30540-6. [Epub ahead of print]

Background: In the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain.

Methods: In this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs.

Findings: Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40 000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40 000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex.

Interpretation: This analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised.

Abstract access 

Europe
France, United Kingdom
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Excessive cardiovascular morbidity and mortality among people living with HIV – preventable with better services?

Editor’s notes: Opportunities to prevent mortality among people living with HIV also include careful attention to risk factors for modifiable cardiovascular health risk factors such as smoking, cholesterol levels, weight and exercise.  In an interesting study from Canada, Jeon and colleagues used the Ontario administrative databases to look at differences between 259 475 people being admitted with acute myocardial infarction according to their HIV status.  Overall, people living with HIV who had heart attacks were around 15 years younger and more than twice as likely to die within 30 days following discharge from the hospital compared to HIV-negative people.  This was not because people living with HIV had received care that was obviously different, with similar rates of revascularisation procedures and follow up visits to the cardiology services.  The study highlights the ongoing uncertainty about the reasons for increased morbidity and mortality among people living with HIV.  However, it is clear that we do have several well proven tools with which to reduce cardiovascular morbidity, so we should ensure that they are incorporated into HIV treatment services.

The relationship between known indicators of cardiovascular risk and HIV were also studied in 67 black South Africans living with HIV.  Borkum and colleagues demonstrate that HIV infection in black South Africans living with HIV was generally well controlled with 84% being virally suppressed and that they had a median CD4 count of over 500 cells per microlitre.  Nonetheless, most had a variety of characteristics that suggest that they were at high risk of cardiovascular events.  Markers of inflammation were raised in 68% and “non-dipping” blood pressure, which is a measure of excessive stiffness of the arteries, was present in 65%.  Straightforward measures that could be made even at the most peripheral ART clinic also demonstrated risk, with 67% being classified as overweight and 76% having an increased waist circumference, both well recognized independent risk factors for cardiovascular disease.  Worryingly this sample, which was largely female (91%), had an average age of only 42 years.  It is clear that intervention on cardiovascular risks is something for all ART providers to consider in every setting.

The Australian Positive and Peers Longevity Evaluation study (beautifully given the acronym of APPLES) also points out the importance of making valid comparisons between people living with HIV and their HIV negative peers.  In Australia, almost half of all people living with HIV are now over the age of 50 years.  Petoumenos and colleagues show that among gay and bisexual men older than 55 years, recruited in Sydney, those living with HIV were more likely to report noncommunicable comorbidities including heart disease and diabetes. However, some of the more obvious risk factors, such as smoking status, were not different between the groups and people living with HIV drank less alcohol than their HIV negative peers.  The relationships between HIV, lifestyle and noncommunicable disease risk are complex but probably important as the population of people living with HIV continues to age.

In a study from the Cohorte de la Red de Investigación en Sida (CoRIS) in Spain, Masiá and colleagues have also explored long term outcomes of almost 9000 people living with HIV and their experience of non-AIDS defining events.  They show that mortality rates are considerably higher in people living with HIV who have any non-AIDS event, even if these are traditionally considered less severe, such as bacterial pneumonia, psychiatric diseases, bone fractures, or diabetes. In addition to standard indicators (such as low CD4 count at ART initiation), we should take the development of non-AIDS events as a warning to intensify management efforts and more targeted prevention of complications.

In the UK, Molloy and colleagues conducted an audit of clinical services provided at different sites.  They show that systems need to catch up with the changes in life experience of people living with HIV.  While sexual health screening was almost universally available, only 71.4% of sites were able to offer cervical cytology despite the increased risk of cervical cancer in women living with HIV.  Less than half of people taking ART had their risk for cardiovascular disease documented.  Regular audit of appropriate services, even with simple checklists for service providers is a strong tool to improve care for people living with HIV and should have a direct impact on mortality.

 

Mortality and health service use following acute myocardial infarction among persons with HIV: a population-based study

 

Jeon C, Lau C, Kendall CE, Burchell AN, Bayoumi AM, Loutfy M, Rourke SB, Antoniou T. AIDS Res Hum Retroviruses. 2017 Sep 14. doi: 10.1089/AID.2017.0128. [Epub ahead of print]

People with HIV have higher rates of acute myocardial infarction (AMI) than HIV-negative individuals. We compared mortality risk and health service use following AMI among people with and without HIV between January 1, 2002, and March 31, 2015. We conducted a population-based study using Ontario's administrative databases. Our primary outcomes were risk of inpatient death and death at 30 days following hospital discharge. In secondary analyses, we compared use of revascularization procedures within 90 days of AMI, as well as readmission or emergency department visits for heart disease and cardiology follow-up within 90 days of discharge. We studied 259 475 AMI patients, of whom 345 (0.13%) were people with HIV. AMI patients with HIV were younger than HIV-negative patients (mean age ± standard deviation: 54.4 ± 10.5 years vs. 69.3 ± 14.3 years). Following multivariable adjustment, the odds ratios for inpatient death and death at 30 days following discharge were 1.04 [95% confidence intervals (CI) 0.64-1.56] and 2.42 (95% CI 1.00-4.92), respectively. In secondary analyses, no differences were observed in receipt of revascularization procedures (hazard ratio (HR) 0.98; 95% CI 0.85-1.12), readmission or emergency department visit for heart disease (HR 1.18; 95% CI 0.85-1.62), or cardiology follow-up (HR 0.88; 95% CI 0.76-1.01). People with HIV experience AMI at younger ages and may be at higher risk of death in the 30 days following hospital discharge, underscoring the importance of targeting modifiable cardiovascular disease risk factors in these patients.

Abstract access

High prevalence of "non-dipping" blood pressure and vascular stiffness in HIV-infected South Africans on antiretrovirals

Borkum MS, Heckmann JM, Manning K, Dave JA, Levitt NS, Rayner BL, Wearne N. PLoS One. 2017 Sep 20;12(9):e0185003. doi: 10.1371/journal.pone.0185003. eCollection 2017.

Background: HIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging ('inflamm-aging'). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population.

Methods: This is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years. Study assessments included: 24hr ABP monitoring, pulse wave velocity (PWV) and central aortic systolic pressure (CASP) using a AtCor Medical Sphygmocor device, fasting lipogram, oral glucose tolerance test, high-sensitivity C-reactive protein (hsCRP) and anthropometric data. Patients completed a questionnaire of autonomic symptoms. CD4+ counts and viral loads were obtained from the National Laboratory results system.

Results: Sixty-seven black participants were included in the analysis of whom 91% (n = 61) were female with a mean age of 42.2 ± 8.6 years. The median duration on ART was 7.5 years (IQR = 6-10), 84% were virally supressed and the median CD4 count was 529.5cells/mm3 (IQR = 372.0-686.5). The majority (67%) were classified as overweight and 76% had an increased waist circumference, yet only 88% of participants were normotensive. A hsCRP level in the high cardiovascular risk category was found in 68% of participants. The prevalence of non-dipping BP was 65%. Interestingly, there was no association on multivariable analysis between dipping status and traditional risk factors for non-dipping BP, such as: obesity, autonomic dysfunction and older age.

Conclusion: This relatively young cross-sectional sample of predominantly normotensive, but overweight black women on effective ART >5 years showed: a high prevalence of non-dipping BP, inflammation and vascular stiffness. Causality cannot be inferred but cardiovascular risk reduction should be emphasized in these patients.  

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Prevalence of self-reported comorbidities in HIV positive and HIV negative men who have sex with men over 55 years—The Australian Positive & Peers Longevity Evaluation Study (APPLES)

Petoumenos K, Huang R, Hoy J, Bloch M, Templeton DJ, Baker D, Giles M, Law MG, Cooper DA. PLoS One. 2017 Sep 8;12(9):e0184583. doi: 10.1371/journal.pone.0184583. eCollection 2017.

In Australia, almost half of HIV-positive people are now aged over 50 and are predominately gay and bisexual men (GBM). Compared to the general HIV-negative population, GBM engage more in behaviours that may increase the risk of age-related comorbidities, including smoking, high alcohol consumption and recreational drug use. The objective of APPLES was to compare comorbidities and risk factors in HIV-positive older GBM with an appropriate control group of HIV-negative GBM. We undertook a prospectively recruited cross-sectional sample of HIV-positive and HIV-negative GBM ≥ 55 years. Detailed data collection included clinic data, a health and lifestyle survey, and blood sample collection. We report key demographic, laboratory markers and self-reported comorbidities by HIV status. For selected comorbidities we also adjust HIV status a priori for age, smoking and body mass index. Over 16 months 228 HIV-positive and 218 HIV-negative men were recruited. Median age was 63 years (IQR: 59-67). Although more HIV-positive men reported having ever smoked, smoking status was not statistically different between HIV positive and HIV negative men (p = 0.081). Greater alcohol use was reported by HIV-negative men (p = 0.002), and recreational drug use reported more often by HIV-positive men (p<0.001). After adjustment, HIV-positive men had significantly increased odds of diabetes (adjusted Odds ratio (aOR): 1.97, p = 0.038), thrombosis (aOR: 3.08, p = 0.007), neuropathy (aOR: 34.6, P<0.001), and non-significantly increased odds for heart-disease (aOR: 1.71, p = 0.077). In conclusion, HIV-positive GBM have significantly increased odds for key self-reported comorbidities. This study underscores the importance of an appropriate HIV-negative control group for more accurate evaluation of the risk and attribution of age-related comorbidities in HIV-positive people.

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Prediction of long-term outcomes of HIV-infected patients developing non-AIDS events using a multistate approach

Masiá M, Padilla S, Moreno S, Barber X, Iribarren JA, Del Romero J, Gómez-Sirvent JL, Rivero M, Vidal F, Campins AA, Gutiérrez F; Cohorte de la Red de Investigación en Sida (CoRIS). PLoS One. 2017 Sep 8;12(9):e0184329. doi: 10.1371/journal.pone.0184329. eCollection 2017.

Objectives: Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013.

Design: Prospective multicenter cohort study.

Methods: Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE".

Results: 8789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval [CI], 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), age >50 years (1.78, 1.08-2.94), hepatitis C-coinfection (2.52, 1.38-4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20-5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01-4.66 for CD4 cell count between 200-350, both compared to CD4 cell count higher than 500) and concomitant CD4 <200 cells/mL (2.22, 1.42-3.44) were associated with death after NAE. CD4 count and HIV-1 RNA at engagement, previous AIDS and hepatitis C-coinfection predicted mortality in NAE-free persons.

Conclusion: NAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts.

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Routine monitoring and assessment of adults living with HIV: results of the British HIV Association (BHIVA) national audit 2015

Molloy A, Curtis H, Burns F, Freedman A; BHIVA Audit and Standards Sub-Committee. BMC Infect Dis. 2017 Sep 13;17(1):619. doi: 10.1186/s12879-017-2708-y.

Background: The clinical care of people living with HIV changed fundamentally as a result of the development of effective antiretroviral therapy (ART). HIV infection is now a long-term treatable condition. We report a national audit to assess adherence to British HIV Association guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals.

Methods: All UK sites known as providers of adult HIV outpatient services were invited to complete a case-note review and a brief survey of local clinic practices. Participating sites were asked to randomly select 50-100 adults, who attended for specialist HIV care during 2014 and/or 2015. Each site collected data electronically using a self-audit spreadsheet tool. This included demographic details (gender, ethnicity, HIV exposure, and age) and whether 22 standardised and pre-defined clinical audited outcomes had been recorded.

Results: Data were collected on 8258 adults from 123 sites, representing approximately 10% of people living with HIV reported in public health surveillance as attending UK HIV services. Sexual health screening was provided within 96.4% of HIV services, cervical cytology and influenza vaccination within 71.4% of HIV services. There was wide variation in resistance testing across sites. Only 44.9% of patients on ART had a documented 10-year CVD risk within the past three years and fracture risk had been assessed within the past three years for only 16.7% patients aged over 50 years.

Conclusions: There was high participation in the national audit and good practice was identified in some areas. However, improvements can be made in monitoring of cardiovascular risk, bone and sexual health.

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Africa, Europe, Northern America, Oceania
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Efforts to understand commercial and transactional sex – involve the community and use both quantitative and qualitative methods

Editor’s notes: As the overall number of new HIV infections falls, it is likely that an increasingly large proportion of infections will occur in key populations and among those left behind by HIV services.  In order to plan, deliver, monitor and evaluate services for specific populations, we need to develop the best estimates possible of the number of people in each population.  Sharifi and colleagues provide an excellent introduction to some of the methods that have been tried to estimate population size of key populations.  Each of the three methods that the authors used to estimate the number of female sex-workers living in urban areas of Iran has strengths and weaknesses.  Used together the methods may allow some triangulation of estimates.  The authors found that the ‘wisdom of the crowds’, in which sex-workers are asked to provide their own best estimates tended to give the highest figures.  The possibility is that where sex work is highly stigmatized and criminalized (as it is in Iran) women may tend to subconsciously exaggerate the numbers in order to normalize their position in society.  Multiplier methods which use “capture-recapture” approaches gave the lowest estimates, which may be due to the same sample of women being seen in both the two approaches used to estimate numbers.  For instance, if some women are more reluctant to be identified, they may be missed both in the distribution of “tags” or gifts and then again in the “re-capture” survey.  The total estimate is then calculated by multiplying the inverse of the proportion of how many women in the survey had received the “tags”.  So, this may produce an underestimate if the same women are missed in both rounds of the research.  Finally, the network methods are used during national surveys and ask respondents to identify how many of their network are sex workers.  Supposedly this avoids the stigma of identifying oneself as a sex worker to the interviewer.  The authors best estimate is that there are more than 200 000 female sex workers in urban settings in Iran, which is considerably higher than the previous estimates.  However, the paper’s key strength is the discussion of the different approaches and how we can improve our understanding of this valuable metric.

The Iranian researchers used a standard definition of sex work, based on having exchanged sex (vaginal, anal, or oral) for money, goods, or favours with at least one male partner in the past 12 months.  However, it is clear that this definition overlaps with many sexual relationships that neither partner would classify as sex work.  Raganathan and colleagues present a fascinating qualitative study of transactional sex and sexual agency among young women in rural South Africa.  Of course, it is not surprising that sex is embedded within a complex framework of romantic relationships that are modified by the degree to which young women values herself and her own agency.  Financial independence is a key to safer relationships, but gifts and money also enhance the status of young women and indicate commitment from their male partner.  It is one thing to count and label sexual transactions, but it is another to understand them and work with young people to enhance their ability to avoid HIV infection.

 

Population size estimation of female sex workers in Iran: synthesis of methods and results

Sharifi H, Karamouzian M, Baneshi MR, Shokoohi M, Haghdoost A, McFarland W, Mirzazadeh A. PLoS One. 2017 Aug 10;12(8):e0182755. doi: 10.1371/journal.pone.0182755. eCollection 2017.

Introduction: Estimating the number of key populations at risk of HIV is essential for planning, monitoring, and evaluating prevention, care, and treatment programmes. We conducted this study to estimate the number of female sex workers (FSW) in major cities of Iran.

Methods: We used three population size estimation methods (i.e., wisdom of the crowds, multiplier method, and network scale-up) to calculate the number of FSW in 13 cities in Iran. The wisdom of the crowds and multiplier methods were integrated into a nationwide bio-behavioural surveillance survey in 2015, and the network scale-up method was included in a national survey of the general population in 2014. The median of the three methods was used to calculate the proportion of the adult female population who practice sex work in the 13 cities. These figures were then extrapolated to provide a national population size estimation of FSW across urban areas.

Results: The population size of FSW was 91 500 (95% Uncertainty Intervals [UIs] 61 400-117 700), corresponding to 1.43% (95% UIs 0.96-1.84) of the adult (i.e., 15-49 years-old) female population living in these 13 cities. The projected numbers of FSW for all 31 provincial capital cities were 130 800 (95% UIs 87 800-168 200) and 228 700 (95% UIs 153 500-294 300) for all urban settings in Iran.

Conclusions: Using methods of comparable rigor, our study provided a data-driven national estimate of the population size of FSW in urban areas of Iran. Our findings provide vital information for enhancing HIV programme planning and lay a foundation for assessing the impact of harm reduction efforts within this marginalized population.

Abstract Full-text [free] access

Young women's perceptions of transactional sex and sexual agency: a qualitative study in the context of rural South Africa

Ranganathan M, MacPhail C, Pettifor A, Kahn K, Khoza N, Twine R, Watts C, Heise L.BMC Public Health. 2017 Aug 22;17(1):666. doi: 10.1186/s12889-017-4636-6

Background: Evidence shows that HIV prevalence among young women in sub-Saharan Africa increases almost five-fold between ages 15 and 24, with almost a quarter of young women infected by their early-to mid-20s. Transactional sex or material exchange for sex is a relationship dynamic that has been shown to have an association with HIV infection.

Methods: Using five focus group discussions and 19 in-depth interviews with young women enrolled in the HPTN 068 conditional cash transfer trial (2011-2015), this qualitative study explores young women's perceptions of transactional sex within the structural and cultural context of rural South Africa. The analysis also considers the degree to which young women perceive themselves as active agents in such relationships and whether they recognise a link between transactional sex and HIV risk.

Results: Young women believe that securing their own financial resources will ultimately improve their bargaining position in their sexual relationships, and open doors to a more financially independent future. Findings suggest there is a nuanced relationship between sex, love and gifts: money has symbolic meaning, and money transfers, when framed as gifts, indicates a young woman's value and commitment from the man. This illustrates the complexity of transactional sex; the way it is positioned in the HIV literature ignores that "exchanges" serve as fulcrums around which romantic relationships are organised. Finally, young women express agency in their choice of partner, but their agency weakens once they are in a relationship characterised by exchange, which may undermine their ability to translate perceived agency into STI and HIV risk reduction efforts.

Conclusions: This research underscores the need to recognise that transactional sex is embedded in adolescent romantic relationships, but that certain aspects make young women particularly vulnerable to HIV. This is especially true in situations of restricted choice and circumscribed employment opportunities. HIV prevention educational programmes could be coupled with income generation trainings, in order to leverage youth resilience and protective skills within the confines of difficult economic and social circumstances. This would provide young women with the knowledge and means to more successfully navigate safer sexual relationships.

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Africa, Asia
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HIV testing and the HIV epidemic –vitally important to prevent HIV becoming endemic

Editor’s notes: Epidemics refer to situations where the number of infections rises (and subsequently falls) more quickly than might be expected compared to a disease that is endemic.  Endemic implies a stable situation, with natural fluctuations in the number of cases.  Medley and Vassal have written a provocative article in Science that considers how differently individuals, communities and society react to epidemic rather than endemic diseases.  They choose to call HIV in 2017 endemic, which carries a serious risk. As the authors state, “The contained public response, and the concurrent shift of responsibility to individuals to protect themselves from risk, means that endemic disease embeds itself further, as those at risk are often the very same people who do not have the private resources to avoid risk or access treatment.”  There are in fact multiple separate epidemics of HIV in different regions and in different populations.  Some are rising and some are falling. The latest UNAIDS’ report emphasizes the heterogeneity of HIV infections in the world.  New HIV infections have fallen by 29% since 2010 in East and Southern Africa, the region with the highest rates.  On the other hand, new HIV infections have risen by an alarming 60% in Eastern Europe and Central Asia over the same period, albeit from a much lower baseline.  There is widespread political consensus to pursue the UN agenda endorsed at the High Level Meeting on Ending AIDS in New York last year.  Let’s not throw in the towel too soon!

HIV testing services remain central to the HIV strategy and, as usual, this month there are several important papers on aspects of HIV testing, many of which illustrate challenges that need to be overcome.

There are several reasons to encourage people living with HIV to know their status.  First and foremost, we know that the earlier treatment is started in the course of HIV, the better the outlook for the individual.  People who start treatment become much less likely to transmit HIV infection to sexual partners. People who know their HIV status are also able to make informed decisions about their lives and their partnerships.  A study this month by Escudero et al. from New York City used agent-based modelling to understand the testing and care continuum for people who inject drugs. Their results remind us of the key role of HIV testing.  They estimated that 53% of the HIV transmission events from people who inject drugs arose from people who did not know their status, and a further 37% from people who had not been started ART.  In other words, they estimate that only 10-11% of infections from people who inject drugs could be prevented by improving quality of care for people on treatment.  The need to find effective ways to encourage people at risk to know their status and start treatment is stark.

Guanzhou is one of the largest cities in China, with a high population of migrants both national and international.  It is among the most prosperous regions of Guangdong province and has the highest rates of HIV.   Chen et al. added some HIV testing related questions to a wider population based health survey in two districts and showed that approximately a quarter of adults had previously been tested for HIV.  HIV testing was almost all provided through free government facilities or blood transfusion centres.  Despite early steps to make HIV self-testing more available, none of the 666 participants who answered the relevant questions in the survey had used a self-test.  Distance from an HIV testing site was a key determinant of the likelihood of getting tested.  It was not clear that people who might be at higher risk were more likely to be tested, although the numbers and sampling focused on the general population rather than people at special risk.

Wang et al. explored the different HIV test kits used in the first line screening in Xi’an.  In line with Chinese guidelines, but not in line with WHO guidance on HIV testing algorithms for low prevalence settings, they used third- or fourth-generation rapid tests and repeated the positive tests.  WHO’s algorithm for low prevalence settings includes three different rapid tests based on different antigens.   Among 665 people found to be positive on rapid tests, only 559 were confirmed to be HIV-positive by Western blotting.  Subsequent follow up with additional Western blots showed that two of the individuals in whom the first Western blot was indeterminate were seroconverting but the other 104 were HIV-negative and had had false-positive results on the original rapid tests.  False positives were more likely with the fourth-generation test (22% of positive tests) compared to the various third-generation tests used (9-11% of positive tests).  Fourth-generation assays are known to be more sensitive, detecting people with HIV around a week or two earlier in the window period than third-generation assays.  However, the authors point out that in low prevalence settings like Xi’an, the known lack of specificity of fourth-generation assays means that they may not provide sufficient advantages to be used as the first line test.  Overall, the paper emphasizes the importance of using clearly defined algorithms.  The WHO algorithms no longer use Western blots, but do recommend using multiple tests based on different antigens for testing people at low risk of infection, and at least two different tests with different antigens for testing people at high risk of infection.  Everyone should have additional confirmatory tests done prior to starting ART.

Harbertson et al. also focused on the accuracy of rapid diagnostic tests.  They screened samples from 459 military personnel in seven African countries who had reported that they were HIV-positive.  Using the WHO algorithm, they compared the results of quality assured HIV testing to the self-reported HIV status of the participants.  They found that, in different country surveys, between three and 91% of people who said that they were living with HIV were in fact HIV-negative.  The authors point out that several studies have demonstrated the importance of following the WHO guidance, and that the positive predictive value of a test (or algorithm) will always fall as the overall prevalence falls.  They discuss possible limitations such as misunderstanding the question or the terminology used, but discount these possibilities as causing many of the false-positive reports, particularly given the highly variable results across different countries.  There was a strong association between the likelihood of a false positive report and lower education level. People whose understanding of HIV was less good were also more likely to report themselves to be positive falsely.  Overall, the authors assume that quality of testing services needs to be an important priority, while not discounting the challenges of using self-reports to collect information about HIV status.

As more and more people chose to know their HIV status, it may be possible to use routine data from the health service to track the epidemiology of HIV, rather than to use special surveys. Traditionally surveys of antenatal mothers have been used to monitor trends in the HIV epidemic over time.  With the widespread adoption of routine testing for mothers, a large proportion of women have an HIV test.  However, the assays used vary.  For surveillance purposes, samples are often stored and transported as dried blood spots and assays are run in batches using automated ELISA technology.  Routine testing (as discussed above) is often done using an algorithm based on a number of different rapid tests.   Pereira et al. have explored the differences between these approaches among almost 40 000 Brazilian mothers who participated in the antenatal surveillance exercise.  They interviewed mothers and linked their routine ANC results to the surveillance database.  Overall the prevalence of HIV among expectant mothers in Brazil was similar whichever approach was used (0.36% or 0.38%).  However, there were interesting differences.  The performance accuracy in those found positive in the surveillance exercise (which was taken as the gold standard) was only 84% overall and varied between regions from 43% to 100%.  So these 14 false negative results among the 88 individuals who were truly positive were compensated for in the overall prevalence estimates by a similar number (18) of false positive results among around 30 000 individuals who were truly negative. This highlights the challenges of providing accurate results to people in low prevalence settings. The 13% of mothers who slipped through the routine services and were not tested or refused to be tested were significantly more likely to be HIV-positive (0.56%), reinforcing the potential biases involved.  Finding 90% of people living with HIV will require considerable attention to the detail and the quality of HIV testing services.

Adolescents are often a population left behind, and regular reports show that adolescents living with HIV are less likely to know their status or to be on treatment or virally supressed.  Simms et al. used provider initiated testing and counselling (PITC) in primary care clinics in Harare, Zimbabwe.  For two years, the research team supported the routine offer of HIV testing to all six to 15 year olds presenting to seven clinics in a well-defined area of Harare.  The authors then conducted a population-based survey to find out how many eight to 17 year olds (who had had two years of exposure to the intervention) were aware of their status. 141 (2.6%) were living with HIV and more than one-third of these were undiagnosed.  Some had rarely been to the clinic, and others had been taken to the clinic by a guardian who was unable to consent to HIV testing on behalf of the child or the child’s parents.  Others had slipped through the PITC net, possibly because, as Lightfoot et al. in an accompanying comment suggest, providers still find it hard to offer HIV tests to everyone, as they assume that people living with HIV will not appear healthy.  This fits with the researchers’ findings that adolescents living with HIV who were currently healthy, had no skin or other problems and had parents who were alive were less likely to be diagnosed.  Both papers suggest that community based testing is needed to find adolescents. However, this also raises challenges in settings with lower prevalence than the high-density suburbs of Harare chosen for this project.  As prevalence falls lower than the 2.6% observed, a huge testing effort is needed, with attendant costs, but also (as explored above) with the risks of inaccurate results and of the very people that we want to find most, not being around for testing at the right moment. 

 

When an emerging disease becomes endemic.

Medley GF, Vassall A. Science. 2017 Jul 14;357(6347):156-158. doi: 10.1126/science.aam8333.

Epidemics, such as HIV in the early 1980s and Ebola in 2014, inspire decisive government investment and action, and individual and societal concern, sometimes bordering on panic. By contrast, endemic diseases, such as HIV in 2017 and tuberculosis, struggle to maintain the same attention. For many, the paradox is that endemic disease, in its totality, continues to impose a far higher public health burden than epidemic disease. Overall, the swift political response to epidemics has resulted in success. It has proven possible to eradicate epidemic diseases, often without the availability of vaccines and other biomedical technologies. In recent times, only HIV has made the transition from epidemic to endemic, but diseases that have existed for centuries continue to cause most of the infectious disease burden.

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The risk of HIV transmission at each step of the HIV care continuum among people who inject drugs: a modeling study.

Escudero DJ, Lurie MN, Mayer KH, King M, Galea S, Friedman SR, Marshall BL. BMC Public Health. 2017 Jul 25;17(1):614. doi: 10.1186/s12889-017-4528-9.

Background: People who inject drugs (PWID) are at continued risk for HIV in the U.S., and experience disparities across the HIV care continuum compared to other high-risk groups. Estimates of the risk of HIV transmission at each stage of the care continuum may assist in identifying public health priorities for averting incident infections among PWID, in addition to transmissions to sexual partners of PWID.

Methods: We created an agent-based model simulating HIV transmission and the HIV care continuum for PWID in New York City (NYC) in 2012. To account for sexual transmission arising from PWID to non-PWID, the simulation included the entire adult NYC population. Using surveillance data and estimates from the National HIV Behavioral Surveillance system, we simulated a dynamic sexual and injecting network. We estimated the proportion of HIV transmission events attributable to PWID in the following categories, those: without an HIV diagnosis ('Undiagnosed'); diagnosed but not on antiretroviral therapy (ART) ('Diagnosed - not on ART'); those who initiated ART but were not virally suppressed ('Unsuppressed'); and, those who achieved viral suppression ('Suppressed').

Results: We estimated HIV incidence among PWID to be 113 per 100 000 person-years in 2012, with an overall incidence rate for the entire adult NYC population of 33 per 100 000 person-years. Despite accounting for only 33% of the HIV-infected PWID population, the Undiagnosed were associated with 52.6% (95% simulation interval [95% SI]: 47.1-57.0%) of total transmission events. The Diagnosed - not on ART population contributed the second-largest proportion of HIV transmissions, with 36.6% (95% SI: 32.2-41.5%). The Unsuppressed population contributed 8.7% (95% SI: 5.6-11.8%), and Suppressed 2.1% (95% SI: 1.1-3.9%), relatively little of overall transmission.

Conclusion: Among PWID in NYC, more than half (53%) of transmissions were from those who were unaware of their infection status and more than 36% were due to PWID who knew their status, but were not on treatment. Our results indicate the importance of early diagnosis and interventions to engage diagnosed PWID on treatment to further suppress population-level HIV transmission. Future HIV prevention research should focus on the elimination of identified and potential barriers to the testing, diagnosis, and retention of PWID on HIV treatment.

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Is there a relationship between geographic distance and uptake of HIV testing services? A representative population-based study of Chinese adults in Guangzhou, China.

Chen W, Zhou F, Hall BJ, Tucker JD, Latkin C, Renzaho AMN, Ling L. PLoS One. 2017 Jul 20;12(7):e0180801. doi: 10.1371/journal.pone.0180801. eCollection 2017.

Achieving high coverage of HIV testing services is critical in many health systems, especially where HIV testing services remain centralized and inconvenient for many. As a result, planning the optimal spatial distribution of HIV testing sites is increasingly important. We aimed to assess the relationship between geographic distance and uptake of HIV testing services among the general population in Guangzhou, China. Utilizing spatial epidemiological methods and stratified household random sampling, we studied 666 adults aged 18-59. Computer-assisted interviews assessed self-reported HIV testing history. Spatial scan statistic assessed the clustering of participants who have ever been tested for HIV, and two-level logistic regression models assessed the association between uptake of HIV testing and the mean driving distance from the participant's residence to all HIV testing sites in the research sites. The percentage of participants who have ever been tested for HIV was 25.2% (168/666, 95%CI: 21.9%, 28.5%), and the majority (82.7%) of participants tested for HIV in Centres for Disease Control and Prevention, public hospitals or STIs clinics. None reported using self-testing. Spatial clustering analyses found a hotspot included 48 participants who have ever been tested for HIV and 25.8 expected cases (Rate Ratio = 1.86, P = 0.002). Adjusted two-level logistic regression found an inverse relationship between geographic distance (kilometers) and ever being tested for HIV (aOR = 0.90, 95%CI: 0.84, 0.96). Married or cohabiting participants (aOR = 2.14, 95%CI: 1.09, 4.20) and those with greater social support (aOR = 1.04, 95%CI: 1.01, 1.07) were more likely to be tested for HIV. Our findings underscore the importance of considering the geographical distribution of HIV testing sites to increase testing. In addition, expanding HIV testing coverage by introducing non-facility based HIV testing services and self-testing might be useful to achieve the goal that 90% of people living with HIV knowing their HIV status by the year 2020.

Abstract  Full-text [free] access

 

The characteristics of screening and confirmatory test results for HIV in Xi'an, China.

Wang L, Zhou KH, Zhao HP, Wang JH, Zheng HC, Yu Y, Chen W. PLoS One. 2017 Jul 7;12(7):e0180071. doi: 10.1371/journal.pone.0180071. eCollection 2017.

Objectives: Individuals with recent or acute HIV infection are more infectious than those with established infection. Our objective was to analyze the characteristics of detection among HIV infections in Xi'an.

Methods: A 4th-generation kit (Architect HIV Ag/Ab Combo) and three 3rd-generationEIA kits (WanTai, XinChuang and Livzon) were used for HIV screening. Overall, 665 individuals were identified as positive and were tested by western blotting (WB). The characteristics of the screening and confirmatory tests were analyzed, including the band patterns, the early detection performance and the false-positive rates.

Results: In total, 561 of the 665 patients were confirmed as having HIV-1 infection, and no HIV-2 specific band was observed. Among these 561 WB-positive cases, reactivity to greater than or equal to 9 antigens was the most commonly observed pattern (83.18%), and the absence of reactivity to p17, p31 and gp41 was detected in 6.44%, 5.9% and 2.86% of the cases, respectively. Two cases were positive by the 4th-generation assay but negative by the 3rd-generation assay for HIV screening and had seroconversion. The false-positive rate of the Architect HIV Ag/Ab Combo (22.01%) was significantly higher than those of WanTai (9.88%), XinChuang (10.87%) and Livzon (8.93%), p<0.05

Conclusion: HIV infection in Xi'an is mainly caused by HIV-1, and individuals are rarely identified at the early phase. Although the false-positive rate of the 4th-generation assay was higher than that of the 3rd-generation assay, it is still recommended for use as the initial HIV screening test for high-risk individuals. In Xi'an, a 3rd-generation assay for screening could be considered.

Abstract  Full-text [free] access

 

Self-reported HIV-positive status but subsequent HIV-negative test result using rapid diagnostic testing algorithms among seven sub-Saharan African military populations.

Harbertson J, Hale BR, Tran BR, Thomas AG, Grillo M, Jacobs MB, McAnany J, Shaffer RA. PLoS One. 2017 Jul 7;12(7):e0180796. doi: 10.1371/journal.pone.0180796. eCollection 2017.

HIV rapid diagnostic tests (RDTs) combined in an algorithm are the current standard for HIV diagnosis in many sub-Saharan African countries, and extensive laboratory testing has confirmed HIV RDTs have excellent sensitivity and specificity. However, false-positive RDT algorithm results have been reported due to a variety of factors, such as suboptimal quality assurance procedures and inaccurate interpretation of results. We conducted HIV serosurveys in seven sub-Saharan African military populations and recorded the frequency of personnel self-reporting HIV positivity, but subsequently testing HIV-negative during the serosurvey. The frequency of individuals who reported they were HIV-positive but subsequently tested HIV-negative using RDT algorithms ranged from 3.3 to 91.1%, suggesting significant rates of prior false-positive HIV RDT algorithm results, which should be confirmed using biological testing across time in future studies. Simple measures could substantially reduce false-positive results, such as greater adherence to quality assurance guidelines and prevalence-specific HIV testing algorithms as described in the World Health Organization's HIV testing guidelines. Other measures to improve RDT algorithm specificity include classifying individuals with weakly positive test lines as HIV indeterminate and retesting. While expansion of HIV testing in resource-limited countries is critical to identifying HIV-infected individuals for appropriate care and treatment, careful attention to potential causes of false HIV-positive results are needed to prevent the significant medical, psychological, and fiscal costs resulting from individuals receiving a false-positive HIV diagnosis.

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Transitioning from antenatal surveillance surveys to routine HIV testing: a turning point in the mother-to-child transmission prevention programme for HIV surveillance in Brazil.

Pereira GFM, Sabidó M, Caruso A, Benzaken AS. BMC Infect Dis. 2017 Jul 5;17(1):469. doi: 10.1186/s12879-017-2540-4.

Background: In Brazil, due to the rapid increase in programmes for the prevention of mother-to-child transmission (PMTCT), routine programme data are widely available. The objective of this study was to assess the utility of programmatic data to replace HIV surveillance based on the antenatal care (ANC) surveillance survey (SS).

Methods: We analysed ANC SS data from 219 maternity service clinics. PMTCT variables were extracted from the ANC SS data collection form, which allowed us to capture and compare the ANC SS data and PMTCT HIV test results for each pregnant woman who completed the ANC SS. Both the PMTCT programme and the ANC SS tested for HIV using sequential ELISA and western blot for confirmation. We assessed the completeness (% missing) of the PMTC data included in the ANC SS.

Results: Of the 36 713 pregnant women who had ANC SS HIV tests performed, 30 588 also underwent PMTCT HIV testing. The HIV prevalence rate from routine PMTCT testing was 0.36%, compared to 0.38% from the ANC SS testing (relative difference -0.05%; absolute difference -0.02%). The relative difference in prevalence rates between pregnant women in northern Brazil and pregnant women central-west Brazil was -0.98 and 0.66, respectively. Of the 29 856 women who had HIV test results from both the PMTCT and ANC SS, the positive percent agreement of the PMTCT versus the surveillance test was 84.1% (95% confidence interval [CI]: 74.8-91.0), and the negative percent agreement was 99.9% (95% CI: 99.9-100.0). The PMTCT HIV testing uptake was 86.4%. The ANC SS HIV prevalence was 0.33% among PMTCT non-refusers and 0.59% among refusers, with a percent bias of -10.80% and a differential prevalence ratio of 0.56. Syphilis and HIV testing results were complete in 98% and 97.6% of PMTCT reports, respectively. The reported HIV status for the women at clinic entry was missing.

Conclusion: Although there were consistent HIV prevalence estimates from the PMTCT data and the ANC SS, the overall positive percent agreement of 84.1% falls below the World Health Organization benchmark of 94.7%. Therefore, Brazil must continue to reinforce data collection practices and ensure the quality of recently introduced rapid HIV testing before replacing the PMTCT data with surveillance techniques. However, some regions with better results could be prioritized to pilot the use of PMTCT data for surveillance.

Abstract  Full-text [free] access

 

Community burden of undiagnosed HIV infection among adolescents in Zimbabwe following primary healthcare-based provider-initiated HIV testing and counselling: A cross-sectional survey.

Simms V, Dauya E, Dakshina S, Bandason T, McHugh G, Munyati S, Chonzi P, Kranzer K, Ncube G, Masimirembwa C, Thelingwani R, Apollo T, Hayes R, Weiss HA, Ferrand RA. PLoS Med. 2017 Jul 25;14(7):e1002360. doi: 10.1371/journal.pmed.1002360. eCollection 2017 Jul.

Background: Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe.

Methods and Findings: Over the course of 2 years (January 2013-January 2015), 7 primary health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC for all attendees aged 6-15 years. In February 2015-December 2015, we conducted a representative cross-sectional survey of 8-17-year-olds living in the 7 communities served by the study PHCs, who would have had 2 years of exposure to PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire, and anonymised HIV testing was carried out using oral mucosal transudate (OMT) tests. After 1 participant taking antiretroviral therapy was observed to have a false negative OMT result, from July 2015 urine samples were obtained from all participants providing OMTs and tested for antiretroviral drugs to confirm HIV status. Children who tested positive through PITC were identified from among survey participants using gender, birthdate, and location. Of 7146 children in 4251 eligible households, 5486 (76.8%) children in 3397 households agreed to participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6% (95% CI 2.2%-3.1%), and over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%-46.2%). Similarly, among the subsample of 2643 (48.2%) participants with a urine test result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%-47.9%). Based on extrapolation from the survey sample to the community, we estimated that PITC over 2 years identified between 18% and 42% of previously undiagnosed children in the community. The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 measures (OMT, self-report, and urine test), none of which were perfect.

Conclusions: Facility-based approaches are inadequate in achieving universal coverage of HIV testing among older children and adolescents. Alternative, community-based approaches are required to meet the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age group.

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Women know what they want, but need more reproductive health choices

Editor’s notes: Eliminating new HIV infections among children is often seen as a useful barometer of the overall success of the health systems as it relates to HIV.  Combination prevention approaches that include structural, behavioural and biomedical elements reduce the chance of women becoming HIV-positive.  Effective provision of a range of choices of modern contraceptive technology allow women to choose whether and when to have babies.  The option B+ approach should ensure that all pregnant women living with HIV are offered lifelong ART, which minimises the chance of mother to child transmission of HIV infection.  Continuing ART treatment for life keeps the mother healthy and allows her to support the development of her infant.

New HIV infections in children have declined by 46% since 2010, but there were still an estimated 160 000 new infections in 2016.  We know that in many settings the health system barometer is still forecasting plenty of clouds among the bright spells.  This month saw a range of papers describing reproductive health choices and HIV, as well as reflections on how option B+ is working, now that it is standard of care.

Contraceptive choices for women at high risk of HIV or living with HIV are complicated.  WHO recently reclassified long-acting progestin injections, such as DMPA, for women at high risk of HIV infection as category 2 in the Medical Eligibility for Contraception guidance. Category 2 means that, although the method is generally safe to use, clinical judgment and careful follow up may be required.  While the evidence comes from meta-analyses of observational studies, with inherent limitations, there is a reliable association between new HIV infection and the use of injectable progestins.  The ongoing randomized ECHO trial will provide higher quality evidence of causality, but results will not be reported until 2019. 

Mayhew et al. found that women living with HIV attending clinics in Kenya, were quite clear about their fertility intentions.  Many did not want more children, although they acknowledged pressure from partners and others.  Stigma around breast-feeding, worries about money and about possible health consequences of pregnancy were all reasons to decide not to have further children. The large majority used various sorts of contraception, but despite this 40% of pregnancies during the study were unintended.  The authors felt that the advice given by the clinics was not adequate and that choice of contraceptive method was limited.  In particular reliable long-acting methods, both reversible and not, were rarely taken up by the younger women.  Overall 16% of women used long-acting methods, and no pregnancies occurred in this group.

Chanda et al. focused on female sex workers in Zambia and found similar results.  Almost half the women had had terminations of pregnancies, and 62% of pregnancies were not planned.  Interestingly the availability of condoms at their places of work reduced the chances of unwanted pregnancy.  Approximately 39% used injectable long-acting contraceptives and only 18% used dual protection with a barrier in addition to a non-barrier method.  Less than one-third of the women reported that condoms were available often or always at work, and 23% reported using no contraception.  Providing access to condoms for sex workers in the highest transmission areas of countries like Zambia seems such an obvious pre-requisite for HIV programmes that it is extraordinary that in 2017 we still do not manage to do so.

Finally on this theme, Salters et al. demonstrate that contraceptive choice for women living with HIV is not only a challenge in sub-Saharan Africa.  The authors followed women in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study and showed that 61% of reported pregnancies were unintended. Women with unintended pregnancies tended to be younger, single and born in Canada compared to women with planned pregnancies.  To support the second prong of the strategy to eliminate HIV infections in children, we need to improve on the integration between services for sexual and reproductive health and rights and services for women living with HIV.

Once women living with HIV are pregnant, the focus shifts to the third and fourth prong – preventing transmission to the infant and keeping the mother and infant healthy.  Option B+ has transformed the approach in most antenatal clinics with high rates of coverage of HIV testing and most women receiving ART during pregnancy.  In the One Stop Clinic in Ifakara, Tanzania, Gamell et al. show that almost all pregnant women, who do not already know that they are living with HIV, are offered an HIV test and that 94% accept it.  Retesting late in pregnancy is not yet routine, and only 3% were re-tested, of whom one (2%) had seroconverted.  Since acute HIV infection has such an important impact on the risk of transmission, re-testing later in pregnancy is now routine in many countries.  Coverage is far from complete, so it is not always clear whether the high rates of seroconversion observed reflect a selection bias in choosing women who are at particularly high risk.  This is an important area for research if we are to continue to drive down the already low transmission rates.  Similarly the authors found that women who slipped through the net and presented in labour, were not always tested and did have a higher prevalence of infection - 5.2% vs. 3.1%. The other significant finding in Ifakara was that, as in many cohort studies, women were happy to take ART during pregnancy to protect their infants, but retention in care thereafter was much less impressive.  Of women newly diagnosed with HIV infection during pregnancy, 27% were lost to follow up at the time of the analysis.

Chadambuka et al. used qualitative methods to understand what impact the shift to option B+ has had in their study area in Zimbabwe.  Overall, the women interviewed were very positive about treatment.  They believed that it was good for their babies and also good for them, making them look healthy and thus avoiding stigma.  However, women pointed out that their male partners are not exposed to as much information at the clinic or in the community.  As a result, many men are less keen to be tested and sometimes not keen for their partners to be taking medicine despite appearing healthy.  As one woman put it: “Very few men are supportive. You have to be strong. The men base their judgment on how healthy you appear to be as you carry yourself around and he also compares to how healthy he feels and opts to delay testing. But delaying only brings further harm. So when those men tell you to stop taking your medication, you need to tell them that they can stop if they want to, whilst you continue with your treatment.”  Within the power dynamics of many relationships, such a forthright approach may not be easy for all women.  So we need continued attention on how to engage men in the process and how to empower women to act as agents of change within their communities.

 

Fertility intentions and contraceptive practices among clinic-users living with HIV in Kenya: a mixed methods study

Mayhew SH, Colombini M, Kimani JK, Tomlin K, Warren CE; Integra Initiative, Mutemwa R. BMC Public Health. 2017 Jul 5;17(1):626. doi: 10.1186/s12889-017-4514-2.

Background: Preventing unwanted pregnancies in Women Living with HIV (WLHIV) is a recognised HIV-prevention strategy. This study explores the fertility intentions and contraceptive practices of WLHIV using services in Kenya.

Methods: Two hundred forty women self-identifying as WLHIV who attended reproductive health services in Kenya were interviewed with a structured questionnaire in 2011; 48 were also interviewed in-depth. STATA SE/13.1, Nvivo 8 and thematic analysis were used.

Results: Seventy one percent participants did not want another child; this was associated with having at least two living children and being the bread-winnerFP use was high (92%) but so were unintended pregnancies (40%) while living with HIV. 56 women reported becoming pregnant "while using FP": all were using condoms or short-term methods. Only 16% participants used effective long-acting reversible contraceptives or permanent methods (LARC-PM). Being older than 25 years and separated, widowed or divorced were significant predictors of long-term method use. Qualitative data revealed strong motivation among WLHIV to plan or prevent pregnancies to avoid negative health consequences. Few participants received good information about contraceptive choices.

Conclusions: WLHIV need better access to FP advice and a wider range of contraceptives including LARC to enable informed choices that will protect their fertility intentions, ensure planned pregnancies and promote safe child-bearing.

Trial registration: Integra is a non-randomised pre-post intervention trial registered with Current Controlled Trials ID: NCT01694862.

Abstract  Full-text [free] access

 

Contraceptive use and unplanned pregnancy among female sex workers in Zambia

Chanda MM, Ortblad KF, Mwale M, Chongo S, Kanchele C, Kamungoma N, Barresi LG, Harling G, Bärnighausen T, Oldenburg CE. Contraception. 2017 Sep;96(3):196-202. doi: 10.1016/j.contraception.2017.07.003. Epub 2017 Jul 12.

Objectives: Access to reproductive healthcare, including contraceptive services, is an essential component of comprehensive healthcare for female sex workers (FSW). Here, we evaluated the prevalence of and factors associated with contraceptive use, unplanned pregnancy, and pregnancy termination among FSW in three transit towns in Zambia.

Study design: Data arose from the baseline quantitative survey from a randomized controlled trial of HIV self-testing among FSW. Eligible participants were 18 years of age or older, exchanged sex for money or goods at least once in the past month, and were HIV-uninfected or status unknown without recent HIV testing (<3 months). Logistic regression models were used to assess factors associated with contraceptive use and unplanned pregnancy.

Results: Of 946 women eligible for this analysis, 84.1% had been pregnant at least once, and among those 61.6% had an unplanned pregnancy, and 47.7% had a terminated pregnancyIncarceration was associated with decreased odds of dual contraception use (aOR=0.46, 95% CI 0.32-0.67) and increased odds of unplanned pregnancy (aOR=1.75, 95% CI 1.56-1.97). Condom availability at work was associated with increased odds of using condoms only for contraception (aOR=1.74, 95% CI 1.21-2.51) and decreased odds of unplanned pregnancy (aOR=0.63, 95% CI 0.61-0.64).

Conclusions: FSW in this setting have large unmet reproductive health needs. Structural interventions, such as increasing condom availability in workplaces, may be useful for reducing the burden of unplanned pregnancy.

Abstract  Full-text [free] access

 

Pregnancy incidence and intention after HIV diagnosis among women living with HIV in Canada

Salters K, Loutfy M, de Pokomandy A, Money D, Pick N, Wang L, Jabbari S, Carter A, Webster K, Conway T, Dubuc D, O'Brien N, Proulx-Boucher K, Kaida A; CHIWOS Research Team. PLoS One. 2017 Jul 20;12(7):e0180524. doi: 10.1371/journal.pone.0180524. eCollection 2017.

Background: Pregnancy incidence rates among women living with HIV (WLWH) have increased over time due to longer life expectancy, improved health status, and improved access to and HIV prevention benefits of combination antiretroviral therapy (cART). However, it is unclear whether intended or unintended pregnancies are contributing to observed increases.

Methods: We analyzed retrospective data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). Kaplan-Meier methods and GEE Poisson models were used to measure cumulative incidence and incidence rate of pregnancy after HIV diagnosis overall, and by pregnancy intention. We used multivariable logistic regression models to examine independent correlates of unintended pregnancy among the most recent/current pregnancy.

Results: Of 1165 WLWH included in this analysis, 278 (23.9%) women reported 492 pregnancies after HIV diagnosis, 60.8% of which were unintendedUnintended pregnancy incidence (24.6 per 1000 women-years (WYs); 95% CI: 21.0, 28.7) was higher than intended pregnancy incidence (16.6 per 1000 WYs; 95% CI: 13.8, 20.1) (Rate Ratio: 1.5, 95% CI: 1.2-1.8). Pregnancy incidence among WLWH who initiated cART before or during pregnancy (29.1 per 1000 WYs with 95% CI: 25.1, 33.8) was higher than among WLWH not on cART during pregnancy (11.9 per 1000 WYs; 95% CI: 9.5, 14.9) (Rate Ratio: 2.4, 95% CI: 2.0-3.0). Women with current or recent unintended pregnancy (vs. intended pregnancy) had higher adjusted odds of being single (AOR: 1.94; 95% CI: 1.10, 3.42), younger at time of conception (AOR: 0.95 per year increase, 95% CI: 0.90, 0.99), and being born in Canada (AOR: 2.76, 95% CI: 1.55, 4.92).

Conclusion: Nearly one-quarter of women reported pregnancy after HIV diagnosis, with 61% of all pregnancies reported as unintended. Integrated HIV and reproductive health care programming is required to better support WLWH to optimize pregnancy planning and outcomes and to prevent unintended pregnancy.

Abstract  Full-text [free] access

 

Prevention of mother-to-child transmission of HIV Option B+ cascade in rural Tanzania: the One Stop Clinic model

Gamell A, Luwanda LB, Kalinjuma AV, Samson L, Ntamatungiro AJ, Weisser M, Gingo W, Tanner M, Hatz C, Letang E, Battegay M; KIULARCO Study Group. PLoS One. 2017 Jul 12;12(7):e0181096. doi: 10.1371/journal.pone.0181096. eCollection 2017.

Background: Strategies to improve the uptake of Prevention of Mother-To-Child Transmission of HIV (PMTCT) are needed. We integrated HIV and maternal, newborn and child health services in a One Stop Clinic to improve the PMTCT cascade in a rural Tanzanian setting.

Methods: The One Stop Clinic of Ifakara offers integral care to HIV-infected pregnant women and their families at one single place and time. All pregnant women and HIV-exposed infants attended during the first year of Option B+ implementation (04/2014-03/2015) were includedPMTCT was assessed at the antenatal clinic (ANC), HIV care and labour ward, and compared with the pre-B+ period. We also characterised HIV-infected pregnant women and evaluated the MTCT rate.

Results: 1579 women attended the ANC. Seven (0.4%) were known to be HIV-infectedOf the remainder, 98.5% (1548/1572) were offered an HIV test94% (1456/1548) accepted and 38 (2.6%) tested HIV-positive51 were re-screened for HIV during late pregnancy and one had seroconvertedThe HIV prevalence at the ANC was 3.1% (46/1463). Of the 39 newly diagnosed women, 35 (90%) were linked to care. HIV test was offered to >98% of ANC clients during both the pre- and post-B+ periods. During the post-B+ period, test acceptance (94% versus 90.5%, p<0.0001) and linkage to care (90% versus 26%, p<0.0001) increasedTen additional women diagnosed outside the ANC were linked to care. 82% (37/45) of these newly-enrolled women started antiretroviral treatment (ART). After a median time of 17 months, 27% (12/45) were lost to follow-up. 79 women under HIV care became pregnant and all received ART. After a median follow-up time of 19 months, 6% (5/79) had been lost. 5727 women delivered at the hospital, 20% (1155/5727) had unknown HIV serostatus. Of these, 30% (345/1155) were tested for HIV, and 18/345 (5.2%) were HIV-positive. Compared to the pre-B+ period more women were tested during labour (30% versus 2.4%, p<0.0001). During the study, the MTCT rate was 2.2%.

Conclusions: The implementation of Option B+ through an integrated service delivery model resulted in universal HIV testing in the ANC, high rates of linkage to care, and MTCT below the elimination threshold. However, HIV testing in late pregnancy and labour, and retention during early ART need to be improved.

Abstract  Full-text [free] access

 

Acceptability of lifelong treatment among HIV-positive pregnant and breastfeeding women (Option B+) in selected health facilities in Zimbabwe: a qualitative study

Chadambuka A, Katirayi L, Muchedzi A, Tumbare E, Musarandega R, Mahomva AI, Woelk G BMC Public Health. 2017 Jul 25;18(1):57. doi: 10.1186/s12889-017-4611-2.

Background: Zimbabwe's Ministry of Health and Child Care (MOHCC) adopted 2013 World Health Organization (WHO) prevention of mother-to-child HIV transmission (PMTCT) guidelines recommending initiation of HIV-positive pregnant and breastfeeding women (PPBW) on lifelong antiretroviral treatment (ART) irrespective of clinical stage (Option B+). Option B+ was officially launched in Zimbabwe in November 2013; however the acceptability of life-long ART and its potential uptake among women was not known.

Methods: A qualitative study was conducted at selected sites in Harare (urban) and Zvimba (rural) to explore Option B+ acceptability; barriers, and facilitators to ART adherence and service uptake. In-depth interviews (IDIs), focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with PPBW, healthcare providers, and community members. All interviews were audio-recorded, transcribed, and translated; data were coded and analyzed in MaxQDA v10.

Results: Forty-three IDIs, 22 FGDs, and five KIIs were conducted. The majority of women accepted lifelong ART. There was however, a fear of commitment to taking lifelong medication because they were afraid of defaulting, especially after cessation of breastfeeding. There was confusion around dosage; and fear of side effects, not having enough food to take drugs, and the lack of opportunities to ask questions in counseling. Participants reported the need for strengthening community sensitization for Option B+. Facilitators included receiving a simplified pill regimen; ability to continue breastfeeding beyond 6 months like HIV-negative women; and partner, community and health worker support. Barriers included distance of health facility, non-disclosure of HIV status, poor male partner support and knowing someone who had negative experience on ART.

Conclusions: This study found that Option B+ is generally accepted among PPBW as a means to strengthen their health and protect their babies. Consistent with previous literature, this study demonstrated the importance of male partner and community support in satisfactory adherence to ART and enhancing counseling techniques. Strengthening community sensitization and male knowledge is critical to encourage women to disclose their HIV status and ensure successful adherence to ART. Targeting and engaging partners of women will remain key determinants to women's acceptance and adherence on ART under Option B+

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Africa, Northern America
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Technology is advancing rapidly, but are we making the most of it?

Editor’s notes: HIV self-testing was a key area of discussion in the Paris IAS meeting.  UNITAID signed the next phase of the STAR Initiative that is working with six countries in Southern Africa to transform the market for self-testing and understand the impact of different delivery systems.  The Bill and Melinda Gates Foundation are using their resources to lower prices of self-test kits.  Following WHO’s decision to prequalify an oral fluid test, many countries are including self-test commodities within their PEPFAR Country Operation Plans and Global Fund concept notes. WHO have issued guidance on self-testing and assisted partner notification. So we can expect to see more and more self-tests out there in the field!

In Malawi, Choko et al. reported on qualitative research done prior to a cluster randomized trial that involves providing self-tests to women attending antenatal care (ANC) for them to take home to their partners.  Although couples are welcomed at ANC clinics and couple testing is certainly beneficial, many men still feel that the clinic is not a place for them.  As one participant said: “Considering what happens here at the ANC clinic, I don’t see my husband escorting me anymore because you find he is alone among many women and he has to listen to some things concerning birth. . . .”

In contrast, many women and men engaged in conversations about how providing self-test kits could help communication, stigma, privacy, control and time pressure among other aspects of involving men in HIV testing.  Some concerns were raised around violence and it is clear that this approach will suit some but not all couples, so it needs to be delivered in a way that respects autonomy with no coercion.

In a very different context, Jamil et al. have conducted a randomized trial among Australian gay men and men who have sex with men.  The trial enrolled “high risk” men who reported multiple partners and condomless sex over the past months.  A central premise of public health strategies to control the HIV epidemic is to find people who have acquired HIV as early as possible.  So the trial aimed to determine whether the offer of free oral fluid self-tests led to earlier testing and more frequent testing.  They found that compared with standard care, availability of free oral-fluid self-testing increased testing frequency both in men who had not tested recently and in men who had not tested at all in the past years. Importantly there was no decline in facility-based testing for HIV or sexually transmitted infections, which might have implied replacement.  The men commented that self-testing was highly acceptable and easy to do.

Self-tests are not a panacea.  Oral fluid tests do have a slightly lower sensitivity than blood based tests.  This may be important when HIV-antibody levels are not high, particularly in people taking ART (either as treatment or as PrEP), or early in the course of infection.  Furthermore, both oral fluid and blood based test rely on visual identification of bands on the test strip that may be faint, leading to some people assuming that they are negative or failing to see the positive band.  Curlin et al. examined the performance of oral fluid tests in people seroconverting to HIV during three specific trials.  They found a considerable number of false negative results and a long delay before some individuals became positive on oral fluid tests.  There was also a clear suggestion that some test operators were less good than others at performing the test and the possibility that one batch of the test kits were less sensitive.  Overall they concluded that “caution must be exercised when interpreting a negative oral fluid test in settings where acute infection is likely, and where PrEP use, ART induced viral suppression, or profound immunosuppression may result in low HIV-specific antibody titers.”  However, as an additional screening tool to be used in populations where many of whom are “missing” from the first 90 are to be found, self-tests have much to offer.  Many of these people will have acquired HIV some time ago and by definition will not be taking ART.  So the cautions raised by Curlin et al. may be less relevant for the primary intended purpose of self-tests.  Nonetheless, they make it very clear that oral fluid self-tests are not an appropriate technology to follow people on treatment or on PrEP.  Nor are they recommended for the diagnosis of acute infection.

While self-tests may increase the proportion of adults knowing their HIV status, different technology is needed for infants.  Nucleic acid amplification is used to detect pro-viral DNA or viral RNA in samples from infants.  The technology is more complex and often centralized, leading to delays and loss to follow up in mother-infant pairs.  Several systems now aim to provide testing close to the point of care and the evaluation of the SAMBA HIV-1 Qual Whole Blood Test from Ondiek et al. is an encouraging report.  Sensitivity and specificity were high (98.5% and 99.8% on 745 infant samples) and comparable to the standard approach used in centralized labs.  Samples from those with discrepant results were rechecked by assays based on multiple targets and suggested that the SAMBA test and the standard approach were each responsible for some of the few false positive and negatives seen.  The advantages of the SAMBA system is that it has been designed to be used in peripheral health systems.  All the reagents are freeze dried and stable without refrigeration. Turnaround time is approximately 2 hours with minimal sample handling once the sample is put into the machine.  Costs will still need to come down, but competition with other manufacturers may help.

The SAMBA technology that was evaluated is a qualitative assay aimed at diagnosis of infants.  A larger market is for viral load assays that are central to the monitoring of the effectiveness of HIV treatment and form the indicator for UNAIDS’s third 90.  However, at the moment viral load assays are still too expensive. As a result the optimal strategy for their use remains uncertain within programmes that have to make difficult decisions about where their limited resources should be spent.

Negoescu et al. have built an interesting model to explore the economic trade-offs between different frequencies of performing viral load assays.  More importantly they explore models of adapting the frequency of assays according to characteristics of the person taking ART.  People who have been on treatment for longer periods, or are older, or report fewer problems with adherence could be selected for less frequent assays.  This could save resources, without compromising health outcomes.  However, for countries like Uganda, which was used as the example to calibrate the model, the best approach seems to still be a viral load assay once per year, regardless of other factors.  And indeed, many resource limited countries are having to make difficult choices about how to allocate stretched budgets between expansion of access to viral load assays to the possible detriment of basic prevention programmes such as male circumcision and condoms.  As more resources become available (or as the cost of viral load assays fall) countries may well choose to do more frequent viral load assays.  The authors showed that monthly assays were more expensive but did (unsurprisingly) lead to benefits in terms of earlier detection of virological failure.  Given the renewed attention to drug resistance and the role of late detection of HIV treatment failure in propagating it, such models may become increasingly important.  Adapting the viral load assay frequency to the characteristics of the person taking HIV treatment could be a sensible approach in middle and higher income settings.

For some years, WHO has recommended that nucleic acid amplification should also be used as the first line test for tuberculosis among people living with HIV.  The GeneXpert® system has been taken up quite widely in many countries where HIV is common among people with tuberculosis, most notably in South Africa.  However, Hermans et al. remind us that technology is only one part of the solution.  Although there is no doubt that Xpert is considerably more sensitive than sputum microscopy and considerably quicker than mycobacterial culture, incorporating the technology into routine practice is not always straightforward.  At the Infectious Disease Institute in Kampala, Uganda, where there are well trained clinicians and better resources than in much of the rest of Uganda, Xpert was made available at no cost for the diagnosis of tuberculosis in a one stop combined HIV-TB clinic.  In a cohort of people living with HIV with symptoms suggestive of possible tuberculosis and whose sputum smear microscopy result was negative, many clinicians still preferred to treat on the basis of their clinical judgement and chest radiography.  Xpert™ was requested in less than half the patients.  Similar numbers of people were started on treatment for tuberculosis regardless of whether Xpert was requested (22% vs 21%).  And among those in whom an Xpert™ was performed, more were started on anti-tuberculosis treatment who had had a negative test than a positive one.  So it was not really clear that Xpert was useful in the diagnosis and management of HIV-related tuberculosis in this setting.  Xpert is not 100% sensitive, so many clinicians will choose to treat patients who might have tuberculosis regardless of the results of new technology.  Xpert also give a result that includes resistance to rifampicin, but this was not such a major issue in Kampala and was not an objective of this study.  Those treated without a confirmed test result were more likely to die during the next 12 months, but the authors point out that there are many possible reasons for this.  Many clinicians are aware of the high rates of undiagnosed tuberculosis found at autopsy in people with HIV. Thus, empirical treatment is often given to those who are critically unwell, even when there is no clear evidence of tuberculosis.

GeneXpert® was also the technology used in another study of tuberculosis contact tracing among school children in Swaziland (Ustero et al.).  Despite a rapid and extensive response to look for additional cases in schools where a confirmed case of tuberculosis had been found, no secondary cases were identified.  In household contacts of the same children, they found an additional two cases.  WHO recommends contacts tracing in households of infectious tuberculosis patients.  Although there is still a large and important gap in the estimated number of tuberculosis cases and the number who are notified and treated by national programmes, the best ways to find the missing cases are not well established.  Even in settings where both infections are among the most important causes of mortality, tuberculosis is much less prevalent than HIV.  So the challenge for case-finding and screening approaches for tuberculosis is to select the populations most at risk. An alternative would be to develop tools that are so sensitive, specific and cheap that they can be used for widespread screening. GeneXpert® is not that tool.

While tuberculosis remains the single most important cause of mortality among people living with HIV in low resource settings, there is welcome and increasing attention being paid to human papillomaviruses (HPV).  Certain types of HPV are the cause of cervical cancer.  This is an AIDS-defining illness both because it is more common among women living with HIV and because it has such a high mortality when only detected at the late stages.  At the Paris conference there was a morning session on how to do more about cervical cancer and in particular how to build on the synergies of both HPV and HIV programmes to provide more integrated services for women who are at risk of both infections.  The most important types of HPV that cause cervical cancer can be prevented by vaccination.  However, to be most effective the vaccine has to be given prior to becoming infected with the relevant HPV strain.  So the study by Sudenga et al. in South Africa is useful as it demonstrates how many younger women aged 16-24 years in the Western Cape Province had antibodies against four of the important types included in the quadrivalent vaccine that they were testing.  The majority of participants (64%) had antibodies to two or more types present at enrolment and 12% had antibodies to all four.  Furthermore, among those participants who received placebo injections, the seroconversion rates were alarming high at 23% for HPV16 and 5% for HPV6 over the 7 months of the study among baseline seronegative participants.  South Africa has been a leader in the region in HPV vaccination for schoolgirls.  It is clear that vaccination needs to happen at a young enough age to catch most girls before they become sexually active.  This is in contrast to the offer of pre-exposure prophylaxis, which should be focused on young women who are already sexually active and at higher risk of acquiring HIV.  The specificities of synergies and integration need to be clearly delineated if we are to maximize efficiency.

HPV is also the principal cause of anal carcinoma, which is a significant problem among gay men and men who have sex with men.  Jin et al. have been building on the progress in cervical cancer screening, where new technologies such as nucleic acid detection or oncoprotein detection are leading to big improvements in some settings and replacing cytology as the first line screen for women.  The authors determined whether similar biomarkers including both nucleic acids and cellular markers could be used instead of anal cytology.  As with most advances in diagnostic technology, there is a trade-off between sensitivity and specificity.  Tests that do not miss any cases of neoplastic change are also likely to lead to many people being unnecessarily referred for further assessment and treatment.  However, both new approaches seem to be able to be calibrated in this Australian population to allow fewer referrals while still maintaining a similar sensitivity to the current cytological approach.

Acceptability of woman-delivered HIV self-testing to the male partner, and additional interventions: a qualitative study of antenatal care participants in Malawi.

Choko AT, Kumwenda MK, Johnson CC, Sakala DW, Chikalipo MC, Fielding K, Chikovore J, Desmond N, Corbett EL. J Int AIDS Soc. 2017 Jun 26;20(1):1-10. doi: 10.7448/IAS.20.1.21610.

Introduction: In the era of ambitious HIV targets, novel HIV testing models are required for hard-to-reach groups such as men, who remain underserved by existing services. Pregnancy presents a unique opportunity for partners to test for HIV, as many pregnant women will attend antenatal care (ANC). We describe the views of pregnant women and their male partners on HIV self-test kits that are woman-delivered, alone or with an additional intervention.

Methods: A formative qualitative study to inform the design of a multi-arm multi-stage cluster-randomized trial, comprised of six focus group discussions and 20 in-depth interviews, was conducted. ANC attendees were purposively sampled on the day of initial clinic visit, while men were recruited after obtaining their contact information from their female partners. Data were analysed using content analysis, and our interpretation is hypothetical as participants were not offered self-test kits.

Results: Providing HIV self-test kits to pregnant women to deliver to their male partners was highly acceptable to both women and men. Men preferred this approach compared with standard facility-based testing, as self-testing fits into their lifestyles which were characterized by extreme day-to-day economic pressures, including the need to raise money for food for their household daily. Men and women emphasized the need for careful communication before and after collection of the self-test kits in order to minimize the potential for intimate partner violence although physical violence was perceived as less likely to occur. Most men stated a preference to first self-test alone, followed by testing as a couple. Regarding interventions for optimizing linkage following self-testing, both men and women felt that a fixed financial incentive of approximately USD$2 would increase linkage. However, there were concerns that financial incentives of greater value may lead to multiple pregnancies and lack of child spacing. In this low-income setting, a lottery incentive was considered overly disappointing for those who receive nothing. Phone call reminders were preferred to short messaging service.

Conclusions: Woman-delivered HIV self-testing through ANC was acceptable to pregnant women and their male partners. Feedback on additional linkage enablers will be used to alter pre-planned trial arms.

Abstract  Full-text [free] access

 

Effect of availability of HIV self-testing on HIV testing frequency in gay and bisexual men at high risk of infection (FORTH): a waiting-list randomised controlled trial.

Jamil MS, Prestage G, Fairley CK, Grulich AE, Smith KS, Chen M, Holt M, McNulty AM, Bavinton BR, Conway DP, Wand H, Keen P,Bradley J, Kolstee J, Batrouney C, Russell D, Law M, Kaldor JM, Guy RJ. Lancet HIV. 2017 Jun;4(6):e241-e250. doi: 10.1016/S2352-3018(17)30023-1. Epub 2017 Feb 17.

Background: Frequent testing of individuals at high risk of HIV is central to current prevention strategies. We aimed to determine if HIV self-testing would increase frequency of testing in high-risk gay and bisexual men, with a particular focus on men who delayed testing or had never been tested before.

Methods: In this randomised trial, HIV-negative high-risk gay and bisexual men who reported condomless anal intercourse or more than five male sexual partners in the past 3 months were recruited at three clinical and two community-based sites in Australia. Enrolled participants were randomly assigned (1:1) to the intervention (free HIV self-testing plus facility-based testing) or standard care (facility-based testing only). Participants completed a brief online questionnaire every 3 months, which collected the number of self-tests used and the number and location of facility-based tests, and HIV testing was subsequently sourced from clinical records. The primary outcome of number of HIV tests over 12 months was assessed overall and in two strata: recent (last test ≤2 years ago) and non-recent (>2 years ago or never tested) testers. A statistician who was masked to group allocation analysed the data; analyses included all participants who completed at least one follow-up questionnaire. After the 12 month follow-up, men in the standard care group were offered free self-testing kits for a year. This trial is registered with the Australian New Zealand clinical trials registry, number actrn12613001236785.

Findings: Between Dec 1, 2013, and Feb 5, 2015, 182 men were randomly assigned to self-testing, and 180 to standard care. The analysis population included 178 (98%) men in the self-testing group (174 person-years) and 165 (92%) in the standard care group (162 person-years). Overall, men in the self-testing group had 701 HIV tests (410 self-tests; mean 4·0 tests per year), and men in the standard care group had 313 HIV tests (mean 1·9 tests per year); rate ratio (rr) 2·08 (95% ci 1·82-2·38; p<0·0001). Among recent testers, men in the self-testing group had 627 tests (356 self-tests; mean 4·2 per year), and men in the standard care group had 297 tests (mean 2·1 per year); rr 1·99 (1·73-2·29; p<0·0001). Among non-recent testers, men in the self-testing group had 74 tests (54 self-tests; mean 2·8 per year), and men in the standard care group had 16 tests (mean 0·7 per year); rr 3·95 (2·30-6·78; p<0·0001). The mean number of facility-based HIV tests per year was similar in the self-testing and standard care groups (mean 1·7 vs 1·9 per year, respectively; rr 0·86, 0·74-1·01; P=0·074). No serious adverse events were reported during follow-up.

Interpretation: HIV self-testing resulted in a two times increase in frequency of testing in gay and bisexual men at high risk of infection, and a nearly four times increase in non-recent testers, compared with standard care, without reducing the frequency of facility-based HIV testing. HIV self-testing should be made more widely available to help increase testing and earlier diagnosis.

Abstract access

 

Analysis of false-negative human immunodeficiency virus rapid tests performed on oral fluid in 3 international clinical research studies.

Curlin ME, Gvetadze R, Leelawiwat W, Martin M, Rose C, Niska RW, Segolodi TM, Choopanya K, Tongtoyai J, Holtz TH, Samandari T, McNicholl JM; OraQuick Study Group. Clin Infect Dis. 2017 Jun 15;64(12):1663-1669. doi: 10.1093/cid/cix228.

Background: The OraQuick Advance Rapid HIV-1/2 Test is a point-of-care test capable of detecting human immunodeficiency virus (HIV)-specific antibodies in blood and oral fluid. To understand test performance and factors contributing to false-negative results in longitudinal studies, we examined results of participants enrolled in the Botswana TDF/FTC Oral HIV Prophylaxis Trial, the Bangkok Tenofovir Study, and the Bangkok MSM Cohort Study, 3 separate clinical studies of high-risk, HIV-negative persons conducted in Botswana and Thailand.

Methods: In a retrospective observational analysis, we compared oral fluid OraQuick (OFOQ) results among participants becoming HIV infected to results obtained retrospectively using enzyme immunoassay and nucleic acid amplification tests on stored specimens. We categorized negative OFOQ results as true-negative or false-negative relative to nucleic acid amplification test and/or enzyme immunoassay, and determined the delay in OFOQ conversion relative to the estimated time of infection. We used log-binomial regression and generalized estimating equations to examine the association between false-negative results and participant, clinical, and testing-site factors.

Results: Two-hundred thirty-three false-negative OFOQ results occurred in 80 of 287 seroconverting individuals.  Estimated OFOQ conversion delay ranged from 14.5 to 547.5 (median, 98.5) days. Delayed OFOQ conversion was associated with clinical site and test operator (P < .05), preexposure prophylaxis (P = .01), low plasma viral load (P < .02), and time to kit expiration (P < .01). Participant age, sex, and HIV subtype were not associated with false-negative results. Long OFOQ conversion delay time was associated with antiretroviral exposure and low plasma viral load.

Conclusions: Failure of OFOQ to detect HIV-1 infection was frequent and multifactorial in origin. In longitudinal trials, negative oral fluid results should be confirmed via testing of blood samples.

Abstract access

 

Multi-country validation of SAMBA - A novel molecular point-of- care test for HIV-1 detection in resource-limited setting.

Ondiek J, Namukaya Z, Mtapuri-Zinyowera S, Balkan S, Elbireer A, Ushiro Lumb I, Kiyaga C, Goel N, Ritchie A, Ncube P, Omuomu K, Ndiege K, Kekitiinwa A,Mangwanya D, Fowler MG, Nadala L, Lee H. J Acquir Immune Defic Syndr. 2017 Jun 9. doi: 10.1097/QAI.0000000000001476. [Epub ahead of print]

Introduction: Early diagnosis of HIV-1 infection and the prompt initiation of antiretroviral therapy are critical to achieving a reduction in the morbidity and mortality of infected infants. The SAMBA HIV-1 Qual Whole Blood Test was developed specifically for early infant diagnosis and prevention of mother-to-child transmission programs implemented at the point-of-care in resource-limited settings.

Methods: We have evaluated the performance of this test run on the SAMBA I semi-automated platform with fresh whole blood specimens collected from 202 adults and 745 infants in Kenya, Uganda, and Zimbabwe. Results were compared with those obtained with the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 assay as performed with fresh whole blood or dried blood spots of the same subjects, and discrepancies were resolved with alternative assays.

Results: The performance of the SAMBA and CAP/CTM assays evaluated at five laboratories in the three countries was similar for both adult and infant samples. The clinical sensitivity, specificity, and positive and negative predictive values for the SAMBA test were 100%, 99.2%, 98.7%, and 100%, respectively, with adult samples, and 98.5%, 99.8%, 99.7%, and 98.8%, respectively, with infant samples.

Discussion: Our data suggest that the SAMBA HIV-1 Qual Whole Blood Test would be effective for early diagnosis of HIV-1 infection in infants at point-of care settings in sub-Saharan Africa.

Abstract access

 

Differentiated human immunodeficiency virus RNA monitoring in resource-limited settings: an economic analysis.

Negoescu DM, Zhang Z, Bucher HC, Bendavid E; Swiss HIV Cohort Study. Clin Infect Dis. 2017 Jun 15;64(12):1724-1730. doi: 10.1093/cid/cix177.

Background: Viral load (VL) monitoring for patients receiving antiretroviral therapy (ART) is recommended worldwide. However, the costs of frequent monitoring are a barrier to implementation in resource-limited settings. The extent to which personalized monitoring frequencies may be cost-effective is unknown.

Methods: We created a simulation model parameterized using person-level longitudinal data to assess the benefits of flexible monitoring frequencies. Our data-driven model tracked human immunodeficiency virus (HIV)-infected individuals for 10 years following ART initiation. We optimized the interval between viral load tests as a function of patients' age, gender, education, duration since ART initiation, adherence behavior, and the cost-effectiveness threshold. We compared the cost-effectiveness of the personalized monitoring strategies to fixed monitoring intervals every 1, 3, 6, 12, and 24 months.

Results: Shorter fixed VL monitoring intervals yielded increasing benefits (6.034 to 6.221 discounted quality-adjusted life-years [QALYs] per patient with monitoring every 24 to 1 month over 10 years, respectively, standard error = 0.005 QALY), at increasing average costs: US$3445 (annual monitoring) to US$5393 (monthly monitoring) per patient, respectively (standard error = US$3.7). The adaptive policy optimized for low-income contexts achieved 6.142 average QALYs at a cost of US$3524, similar to the fixed 12-month policy (6.135 QALYs, US$3518). The adaptive policy optimized for middle-income resource settings yields 0.008 fewer QALYs per person, but saves US$204 compared to monitoring every 3 months.

Conclusions: The benefits from implementing adaptive vs fixed VL monitoring policies increase with the availability of resources. In low- and middle-income countries, adaptive policies achieve similar outcomes to simpler, fixed-interval policies.

Abstract  Full-text [free] access

 

Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert™ MTB/RIF era: a cohort study.

Hermans SM, Babirye JA, Mbabazi O, Kakooza F, Colebunders R, Castelnuovo B, Sekaggya-Wiltshire C, Parkes-Ratanshi R, Manabe YC. BMC Infect Dis. 2017 Jun 16;17(1):433. doi: 10.1186/s12879-017-2534-2.

Background: The Xpert™ MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP).

Methods: Prospective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda. Prior to testing clinicians were asked to decide whether they would treat empirically prior to Xpert result; actual treatment was decided upon receipt of the XP result. We compared empirical and XP-informed treatment decisions and all-cause mortality in the first year.

Results: Of 411 smear-negative presumptive TB patients, 175 (43%) received an XP; their baseline characteristics did not differ. XP positivity was similar in patients with a pre-XP empirical diagnosis and those without (9/29 [17%] versus 14/142 [10%], P = 0.23). Despite XP testing high levels of empirical treatment prevailed (18%), although XP results did change who ultimately was treated for TB. When adjusted for CD4 count, empirical treatment was not associated with higher mortality compared to no or microbiologically confirmed treatment.

Conclusions: XP usage was lower than expected. The lower sensitivity of XP in smear-negative HIV-positive patients led experienced clinicians to use XP as a "rule-in" rather than "rule-out" test, with the majority of patients still treated empirically.

Keywords: Empirical treatment; HIV Infections/complications; Molecular diagnostic techniques/methods; Tuberculosis, pulmonary/diagnosis; Tuberculosis, pulmonary/epidemiology

Abstract  Full-text [free] access 

 

School and household tuberculosis contact investigations in Swaziland: Active TB case finding in a high HIV/TB burden setting.

Ustero PA, Kay AW, Ngo K, Golin R, Tsabedze B, Mzileni B,Glickman J, Wisile Xaba M, Mavimbela G, Mandalakas AM. PLoS One. 2017 Jun 5;12(6):e0178873. doi: 10.1371/journal.pone.0178873.eCollection 2017.

Background: Investigation of household contacts exposed to infectious tuberculosis (TB) is widely recommended by international guidelines to identify secondary cases of TB and limit spread. There is little data to guide the use of contact investigations outside of the household, despite strong evidence that most TB infections occur outside of the home in TB high burden settings. In older adolescents, the majority of infections are estimated to occur in school. Therefore, as part of a project to increase active case finding in Swaziland, we performed school contact investigations following the identification of a student with infectious TB.

Methods: The Butimba Project identified 7 adolescent TB index cases (age 10-20) with microbiologically confirmed disease attending 6 different schools between June 2014 and March 2015. In addition to household contact investigations, Butimba Project staff worked with the Swaziland School Health Programme (SHP) to perform school contact investigations. At 6 school TB screening events, between May and October 2015, selected students underwent voluntary TB screening and those with positive symptom screens provided sputum for TB testing.

Results: Among 2015 student contacts tested, 177 (9%) screened positive for TB symptoms, 132 (75%) produced a sputum sample, of which zero tested positive for TB. Household contact investigations of the same index cases yielded 40 contacts; 24 (60%) screened positive for symptoms; 19 produced a sputum sample, of which one case was confirmed positive for TB. The odds ratio of developing TB following household vs. school contact exposure was significantly lower (OR 0.0, 95% CI 0.0 to 0.18, P = 0.02) after exposure in school.

Conclusion: School-based contact investigations require further research to establish best practices in TB high burden settings. In this case, a symptom-based screening approach did not identify additional cases of tuberculosis. In comparison, household contact investigations yielded a higher percentage of contacts with positive TB screens and an additional tuberculosis case.

Abstract Full-text [free] access

 

HPV serostatus pre- and post-vaccination in a randomized phase II preparedness trial among young Western Cape, South African women: the EVRI trial.

Sudenga SL, Torres BN, Botha MH, Zeier M, Abrahamsen ME, Glashoff RH, Engelbrecht S, Schim Van der Loeff MF, Van der Laan LE, Kipping S, Taylor D, Giuliano AR. Papillomavirus Res. 2017 Jun;3:50-56. doi: 10.1016/j.pvr.2017.02.001. Epub 2017 Feb 16.

Background: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women.

Methods: Women aged 16-24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type.

Results: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6.

Conclusion: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut.

Abstract access

 

The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men.

Jin F, Roberts JM, Grulich AE, Poynten IM, Machalek DA, Cornall A, Phillips S, Ekman D, McDonald RL, Hillman RJ, Templeton DJ, Farnsworth A, Garland SM, Fairley CK, Tabrizi SN; SPANC Research Team. AIDS. 2017 Jun 1;31(9):1303-1311. doi: 10.1097/QAD.0000000000001462.

Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia.

Design: Baseline analysis of a 3-year cohort study.

Methods: The study of the prevention of anal cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers.

Results: The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005).

Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.

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Africa, Asia, Europe, Oceania
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Some key considerations for surveys of key populations

Editor’s notes: A key challenge for epidemiological research involving key populations is to find a representative sample.  Whereas national surveys such as demographic health surveys (DHS) and PHIA can use the total population to create a sampling frame from which to draw individuals at random, researchers interested in key populations have to use a range of methods, all of which have limitations as well as strengths.  Internet and app-based surveys may accrue large numbers, but may have significant biases in terms of who chooses to answer such questionnaires.  Venue-based sampling allows data to be collected from people who happen to be at the venue at the same time as the researchers.  Respondent driven sampling has become increasingly popular as a method to reach individuals that might otherwise be hard to include in studies.  Increasingly sophisticated statistical methods have been developed to adjust estimates, and in particular their precision, according to characteristics of respondents found in the sample.

This month we have three respondent driven studies that highlight different methodological aspects as well as shedding light on key populations in Africa and Asia.  Hladik et al. conducted a major survey of female sex workers in Kampala, Uganda.  Unfortunately, it has taken some time for this study to be published, as the original questionnaires were completed in 2008/9 and it is plausible that many aspects of sex work have been changing over the past decade.  Nonetheless, the authors succeeded in enrolling almost 1000 female sex workers from the capital city using a respondent driven sampling approach.  The authors paid close attention to methods that could maximize the validity of the data they collected as well as ensuring that participants were protected.  Formative research laid out acceptable incentives to participate, as well as approaches to discuss sensitive or taboo areas and to ensure that all the women understood what was being asked in particular questions.  Finger scanners were used to generate unique identification numbers, so that women could be tracked during the study, and these files were subsequently deleted.  This approach was widely accepted, as it has been in many programmes offering services that benefit from a linked identifier.  However, any approach that creates identifiers for populations that are often discriminated or legislated against needs to be examined critically to ensure that any risks to participants are well understood, particularly for research that is not going to bring any direct benefits to the individual participants.  Although the study’s findings are not particularly surprising, they remind us that sex workers in Kampala need to remain a vital part of the HIV response.  Not only are they affected by a high prevalence of 33%, rising to 44% among those over 25 years old, but they are also subject to horribly high rates of violence including both rape and beating in up to one third of the women in the one month prior to the interview.  The study highlights particular factors that might help identify women in most need of HIV and other services.  Women with less education, who rely entirely on sex work for their income and who have never tested for HIV are all more likely to be HIV positive.

In nearby Malawi, Wirtz et al. point out that many respondent driven samples of key populations, such as that from Hladik et al., are only able to collect data from one particular city or region, and that this can lead to misinterpretation if the results are generalized to whole countries.  The authors conducted a large study of gay men and men who have sex with men in seven different communities across Malawi.  They found considerable heterogeneity leading to an overall estimate that the risk of HIV was approximately twice as high in gay men and men who have sex with men as in the general population of men of the same age.  The study managed to enrol a total of almost 2500 men through respondent driven sampling in the different districts.  However, this was at the expense of having to collect data over a considerable time period, with the study team moving from district to district.  As the authors acknowledge, the risk is that data collected in the most recent time period may not be equivalent to data collected four years previously.  The authors did find that the highest rates of HIV among gay men and men who have sex with men were not always where they have been presumed to be.  In particular tourist areas and some rural areas had higher rates than some of the cities that are usually the focus of key populations programmes.  Once again, the finding that so few gay men and men who have sex with men knew their status and were linked to treatment may not be surprising but is still shocking.  Only 1% of men found to be positive reported that they were aware of their status.  The authors point out the tension between public health and policy in a country where homosexuality is criminalized.  If HIV is to be prevented, this tension will need to be resolved.

The third respondent driven sampling study also highlights heterogeneity.  Verdery et al. used additional statistical methods to study the network characteristics of people who use drugs in two cities in the Philippines (Cebu and Mandaue).  The “small world” phenomenon explains how in more closed settings everyone knows everyone else, and among people who use drugs, many people form part of overlapping networks of needle sharing that allow for rapid propagation of infection.  Developing such methods could allow respondent driven samples to yield greater insights in to the epidemiology of HIV in key populations.  However, issues of representation both of the sample interviewed and of the broader geographic population of interest will remain important.  Quantitative research is certainly essential to understand the population sizes of key populations, and their prevalence, incidence and risk factors of HIV infection.  However, research into policy formation; social science research to understand the larger context of HIV and implementation science to determine how better to offer services that engage individuals in HIV testing and care remain a high priority. 

Burden and characteristics of HIV infection among female sex workers in Kampala, Uganda - a respondent-driven sampling survey

Hladik W, Baughman AL, Serwadda D, Tappero JW, Kwezi R, Nakato ND, Barker J. BMC Public Health. 2017 Jun 10;17(1):565. doi: 10.1186/s12889-017-4428-z.

Background: Sex workers in Uganda are at significant risk for HIV infection. We characterized the HIV epidemic among Kampala female sex workers (FSW).

Methods: We used respondent-driven sampling to sample FSW aged 15+ years who reported having sold sex to men in the preceding 30 days; collected data through audio-computer assisted self-interviews, and tested blood, vaginal and rectal swabs for HIV, syphilis, neisseria gonorrhea, chlamydia trachomatis, and trichomonas vaginalis.

Results: A total of 942 FSW were enrolled from June 2008 through April 2009. The overall estimated HIV prevalence was 33% (95% confidence intervals [CI] 30%-37%) and among FSW 25 years or older was 44%. HIV infection is associated with low levels of schooling, having no other work, never having tested for HIV, self-reported genital ulcers or sores, and testing positive for neisseria gonorrhea or any sexually transmitted infections (STI). Two thirds (65%) of commercial sex acts reportedly were protected by condoms; one in five (19%) FSW reported having had anal sex. Gender-based violence was frequent; 34% reported having been raped and 24% reported having been beaten by clients in the preceding 30 days.

Conclusions: One in three FSW in Kampala is HIV-infected, suggesting a severe HIV epidemic in this population. Intensified interventions are warranted to increase condom use, HIV testing, STI screening, as well as antiretroviral treatment and pre-exposure prophylaxis along with measures to overcome gender-based violence.

Abstract  Full-text [free] access

 

Geographical disparities in HIV prevalence and care among men who have sex with men in Malawi: results from a multisite cross-sectional survey.

Wirtz AL, Trapence G, Kamba D, Gama V, Chalera R, Jumbe V, Kumwenda R, Mangochi M, Helleringer S, Beyrer C, Baral S. Lancet HIV. 2017 Jun;4(6):e260-e269. doi: 10.1016/S2352-3018(17)30042-5. Epub 2017 Feb 28.

Background: Epidemiological assessment of geographical heterogeneity of HIV among men who have sex with men (MSM) is necessary to inform HIV prevention and care strategies in the more generalised HIV epidemics across sub-Saharan Africa, including Malawi. We aimed to measure the HIV prevalence, risks, and access to HIV care among MSM across multiple localities to better inform HIV programming for MSM in Malawi.

Methods: Between Aug 1, 2011, and Sept 13, 2014, we recruited MSM into cross-sectional research via respondent-driven sampling (RDS) in seven districts of Malawi. RDS and site weights were used to estimate national HIV prevalence and engagement in care and in multilevel regression models to identify correlates of prevalent HIV infection. The comparative prevalence ratio of HIV among MSM relative to adult men was calculated by use of direct age-stratification.

Findings: 2453 MSM were enrolled with a population HIV prevalence of 18·2% (95% CI 15·5-21·2), as low as 4·1% (2·2-7·6) in Mzuzu and as high as 24·5% (19·5-30·3) in Mulanje. The comparative HIV prevalence ratio was 2·52 when comparing MSM with the adult male population. Age-stratified HIV prevalence showed early onset of infection with 11·8% (95% CI 7·3-18·4) of MSM aged 18-19 years HIV infected. Factors positively associated with HIV infection included being aged 21-30 years and reporting female or transgender identity. Among HIV infected MSM, less than 1% reported ever being diagnosed with HIV infection (0·9%, 95% CI 0·4-2·5) and initiated antiretroviral treatment (0·2%, 0·2-0·3).

Interpretation: HIV disproportionately affects MSM in Malawi with disparities sustained across the HIV care continuum. These issues are geographically heterogeneous and begin among young MSM, supporting geographically focused and age-specific approaches to confidential HIV testing with linkage to HIV services. 

Abstract access 

 

Social network clustering and the spread of HIV/AIDS among persons who inject drugs in two cities in the Philippines

Verdery AM, Siripong N, Pence BW. J Acquir Immune Defic Syndr. 2017 Sep 1;76(1):26-32. doi: 10.1097/QAI.0000000000001485. Epub 2017 Jun 22.

Introduction: The Philippines has seen rapid increases in HIV prevalence among people who inject drugs. We study two neighboring cities where a linked HIV epidemic differed in timing of onset and levels of prevalence. In Cebu, prevalence rose rapidly from under 1% to 54% between 2009 and 2011 and remained high through 2013. In nearby Mandaue, HIV remained below 4% through 2011 then rose rapidly to 38% by 2013.

Objectives: We hypothesize that infection prevalence differences in these cities may owe to aspects of social network structure, specifically levels of network clustering. Building on prior research, we hypothesize that higher levels of network clustering are associated with greater epidemic potential.

Methods: Data were collected with respondent-driven sampling among males who inject drugs in Cebu and Mandaue in 2013. We first examine sample composition using estimators for population means. We then apply new estimators of network clustering in respondent-driven sampling data to examine associations with HIV prevalence.

Results: Samples in both cities were comparable in terms of composition by age, education, and injection locations. Dyadic needle sharing levels were also similar between the two cities, but network clustering in the needle sharing network differed dramatically. We found higher clustering in Cebu than Mandaue, consistent with expectations that higher clustering is associated with faster epidemic spread.

Conclusion: This paper is the first to apply estimators of network clustering to empirical respondent-driven samples, and it offers suggestive evidence that researchers should pay greater attention to network structure's role in HIV transmission dynamics.

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Africa, Asia
Malawi, Philippines, Uganda
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How are we going to get to our prevention targets? Old tools, new tools and a more nuanced understanding of transmission dynamics.

Editor’s notes: By 2020, the Fast-Track strategy is aiming to reduce new HIV infections to 200 000 per year.  There is increasing recognition that if we are to succeed, we will need to do much more than simply putting people onto HIV treatment.  Despite the massive impact of ART on infectiousness, the decline in new infections at the community level is still not fast enough, even in countries like Botswana (see above) where 90-90-90 has almost been reached.  Renewed enthusiasm for primary prevention has also followed key trials of biomedical prevention tools including voluntary medical male circumcision and ARV-based prevention.  It is all too easy for us to forget the crucial role that condoms have played from the early days of the epidemic.  More recently, with HIV seen as a less terrifying infection, many programmes suffer from “condom fatigue”.  So it is good to see papers on the key importance of condoms as well as perspectives on how they are perceived by young men.

The magic of ARVs does not end with treatment.  We are finally moving to wider use of pre-exposure prophylaxis (PrEP).  There is no doubt that PrEP works when taken, but there are still plenty of questions for policy-makers about how to adopt it whole-heartedly into their national strategic plans and for financiers about how to pay for it.  Papers this month cover a range of experiences with PrEP from the US, where the huge majority of PrEP users still live, to Europe and Australia, where policies are finally moving towards wider use.  Long acting PrEP remains a key objective for many, as it might improve regular adherence, which has proved the Achilles’ heel of oral and topical PrEP in several of the large studies.

One of the ways to make PrEP most cost-effective is to ensure that it is available to people who are most likely to acquire HIV.  So the hope continues that phylogenetic analyses will allow more sophisticated understanding of the dynamics of the multiple overlapping networks of HIV transmission in communities.  Papers this month cover Australia and the PANGEA consortium of African research sites along with a cautionary comment about establishing the ethical framework for such studies, particularly among populations who are already subject to discrimination and criminalization.

When used correctly and consistently, condoms are highly effective not only to prevent HIV but also to prevent pregnancy and to prevent sexually transmitted infections.  Stover and colleagues have tried to capture all three benefits in one model.  They explore three potential scenarios for condom programming between now and 2030 in 81 countries that are priorities for family planning or HIV programmers or both.  The benefits of greater investment in condoms are huge.  In their most optimistic scenario, the authors suggest that if the entire gap between people who would like to use condoms and people who currently use them was filled (almost 11 billion condoms over the period), this could prevent up to 400 million unwanted pregnancies; 16.8 million new HIV infections and more than 700 million sexually transmitted infections.  The costs are quite modest, and at $115 per DALY averted this is an investment that everyone should support.  There are of course limitations in such a broad brush model, but it provides an excellent starting point.

The challenges in provision of condoms to young people go well beyond the cost and effectiveness considerations that underpin the previous analysis.  In an interesting qualitative study in South Africa, de Bruin and Panday-Soobrayan report their findings from focus group discussions with learners in 33 public schools.  Most of the learners were not in favour of provision of condoms at school, although they were keen on more youth friendly sexual and reproductive health and rights services within the public sector.  Many thought that provision of condoms would lead to earlier and more frequent sexual contacts, despite considerable experience showing that this is not the case in other settings.

Multiple trials have shown that PrEP is extremely effective when it is used consistently and correctly.  Many countries in all continents are now beginning to work out where it fits within their combination prevention package.  To date, the large majority of PrEP users are in the United States of America (USA), where more than 140 000 people have started.  It is much harder to measure how many are still taking it regularly.  Patel and colleagues analysed utilization at three months after the initial prescription of PrEP in three major PrEP clinics in three states in the USA.  18% of the 201 people (90% male) seen at baseline did not use their PrEP and this was strongly predicted by insurance status, with around a four-fold risk of dropping out among those who were not insured.  Although the numbers are small, this is an important study.  The authors suggest that increased insurance cover might make PrEP have a greater impact.  More broadly it raises the challenge that PrEP is often needed most by people least able to access it.  This will be a real challenge in countries where people most at risk, such as gay men and other men who have sex with men and sex workers, are criminalized or discriminated against in many health care settings.

In Australia, PrEP has been provided through large demonstration projects while awaiting decisions about how to include it in routine practice.  Lal and colleagues report results from 114 (one transgender woman, the rest male) people taking PrEP in the Victorian PrEP Demonstration project.  Participants have to pay an equivalent of an insurance co-payment, in order to make the situation more like the “real world”.  The participants were recruited because they were at high risk of HIV engaging in condomless anal sex with partners who were known to be living with HIV or of unknown status.  Adherence to PrEP was excellent as measured by a variety of reported and biological measures.  They observed one seroconversion in a man with exposure two weeks before starting PrEP who was already in the process of seroconverting and whose virus was found to be resistant to emtricitabine.  The only other seroconversion occurred in someone who had not yet started PrEP.  The authors found a substantial increase in rates of gonorrhoea and chlamydia once participants were “stable” on PrEP after three months.  There was also a significant reduction in condom use with both regular and casual partners.  This is one of the first studies to document important risk compensation among PrEP users.  Of course, preventing HIV is a huge benefit that generally outweighs the harms of additional treatment for sexually transmitted infections.  However, the study emphasizes the importance of enhancing sexual health services alongside PrEP and reminds us that people most at risk of HIV are also at high risk of other infections (and also of pregnancy in the context of heterosexual transmission.)  If PrEP is integrated within a broad sexual health service, there could be considerable synergistic benefits.

Gay men and men who have sex with men who enrolled in the PrEP demonstration project in Amsterdam also had high concomitant rates of hepatitis C virus (HCV).  Hoorenborg and colleagues found that around 5% of the 375 men enrolled in the project were co-infected.  The HCV found among these men were genetically similar to those circulating in the population of gay men and other men who have sex with men living with HIV, and more distinct from HCV from other risk groups.  This is good evidence that HCV and HIV both circulate in this population, and emphasizes once again the need for more integrated services, including hepatitis screening.

The ÉCLAIR study is a phase 2a trial of cabotegravir injections in healthy HIV-negative male volunteers.  As noted, adherence is a major challenge in many PrEP trials; although notably less of a problem when people choose to take PrEP in demonstration projects.  It is hoped that cabotegravir could be the first long acting PrEP.  Markowitz and colleagues presented the results of this study at CROI 2017.  The authors point out that although the injections are painful, many men stated that they would be happy to continue if the injections were effective.  No serious safety challenges emerged. The pharmacokinetics suggests that a dose given more frequently will be needed – and subsequent trials will use a two monthly regimen. 

One group for whom PrEP has been recommended by WHO for some years are serodiscordant couples (SDCs).  The Partners PrEP study, which forms one of the cornerstones for the evidence that PrEP works for both men and women, was conducted in SDCs.  The idea is to protect the HIV-negative partner from infection until such time as the partner living with HIV has been on ART consistently and suppressed their viral load.  So a study from the Centers for Disease Control USA is relevant to discussions of PrEP.  Crepaz and colleagues found that around 6000 new HIV infections occur each year in the USA among men and women having heterosexual sex and are aware that their partner is living with HIV.  They point out that viral suppression is achieved by only around 50% of heterosexuals living with HIV and that an additional proportion does not know their HIV status.  So the importance of HIV testing, and of focusing efforts on serodiscordant couples is clear.  Such efforts include both improving HIV treatment effectiveness, and providing a range of prevention choices including PrEP until viral suppression is achieved.

While the study above used traditional epidemiological surveillance reports, phylogenetics may provide additional insights into the dynamics of transmission.  In Australia, where notifications with HIV are rising steadily,  Castley and colleagues have examined the sequence data from almost 5000 viruses collected across the country from 2005-2012.  This sample is drawn from around 1200 new HIV infections per year (and around 27 000 people living with HIV).  The sample is not random, but reflects samples that were sent for sequencing to determine drug resistance.  Around one quarter of sequences are found in tight clusters (pairs, triplets or more) with other sequences, making it likely that they are closely connected by transmission.  Of course, all HIV sequences have been transmitted, so a longer time period and complete sampling would be expected to give a much higher proportion in clusters.  Indeed the more recent samples are around twice as likely to be in clusters as those collected at the start of the time period. Nonetheless, the large sample and the time period of collection allows some clear observations to be made.  In all states, the proportion of non-B subtypes is increasing, which must relate to travel and migration to and from Asia and Africa.  There is little evidence that the C subtypes (originally from Africa) are found in all male clusters suggesting little spill over into the community of gay men and other men having sex with men.  Larger clusters are more common among younger, all male networks. Like most molecular epidemiological studies, there are a small number of large clusters which represent highly active transmission.  These clusters are also most likely to be all male.  Taken together, the results suggest that the steady rise in notifications in Australia is probably due to increasing migration and travel and to ongoing active transmission networks among young gay men.  The challenge is to turn this sort of analysis into clear policy recommendations that can improve HIV prevention.

UNAIDS joined an interesting meeting on the ethics of phylogenetic studies in Africa organised by the PANGEA consortium.  Many of the issues discussed are also covered in a comment by Cohen on the importance of thinking through the risks inherent in these studies.  A key issue is to ensure that systems are reinforced to monitor any unexpected harms and to establish mitigation strategies to minimize them.  The challenges are not necessarily different to traditional epidemiological studies which may highlight networks and locations of groups that are criminalized or discriminated against.  In community consultations, prior to agreeing to go forward with phylogenetic studies, some potential participants even say that they would be keen to “know who infected them” in order to punish them.  This is clearly NOT the aim of such studies and emphasizes the importance of clear information about the limitations of the techniques which cannot usually rule out the possibility of additional links in the transmission chain.  Issues of anonymised information and what to do if clinically relevant results such as drug resistance mutations are uncovered as incidental findings also need to be discussed.

Furthermore, Ratmann and colleagues, reporting on the first 4000 sequences from the PANGEA consortium (largely from the Rakai project in Uganda), also emphasize some of the technical challenges that may lead to erroneous results in creating phylogenies.  There is little doubt that as the cost of sequencing falls and as the technologies and software become increasingly straightforward, we will see more and more studies of sequence data.  It is likely that analysis of these data will lead to more nuanced approaches to HIV prevention, particularly as the overall incidence falls, and sharper tools are needed to dissect the pathways of ongoing transmission.

The case for investing in the male condom

Stover J, Rosen JE, Carvalho MN, Korenromp EL, Friedman HS, Cogan M, Deperthes B. PLoS One. 2017 May 16;12(5):e0177108. doi: 10.1371/journal.pone.0177108. eCollection 2017.

When used correctly and consistently, the male condom offers triple protection from unintended pregnancy and the transmission of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). However, with health funding levels stagnant or falling, it is important to understand the cost and health impact associated with prevention technologies. This study is one of the first to attempt to quantify the cost and combined health impact of condom use, as a means to prevent unwanted pregnancy and to prevent transmission of STIs including HIV. This paper describes the analysis to make the case for investment in the male condom, including the cost, impact and cost-effectiveness by three scenarios (low in which 2015 condom use levels are maintained; medium in which condom use trends are used to predict condom use from 2016-2030; and high in which condom use is scaled up, as part of a package of contraceptives, to meet all unmet need for family planning by 2030 and to 90% for HIV and STI prevention by 2016) for 81 countries from 2015-2030. An annual gap between current and desired use of 10.9 billion condoms was identified (4.6 billion for family planning and 6.3 billion for HIV and STIs). Under a high scenario that completely reduces that gap between current and desired use of 10.9 billion condoms, we found that by 2030 countries could avert 240 million DALYs. The additional cost in the 81 countries through 2030 under the medium scenario is $1.9 billion, and $27.5 billion under the high scenario. Through 2030, the cost-effectiveness ratios are $304 per DALY averted for the medium and $115 per DALY averted for the high scenario. Under the three scenarios described above, our analysis demonstrates the cost-effectiveness of the male condom in preventing unintended pregnancy and HIV and STI new infections. Policy makers should increase budgets for condom programming to increase the health return on investment of scarce resources.

Abstract  Full-text [free] access

Learners' perspectives on the provision of condoms in South African public schools.

de Bruin WE, Panday-Soobrayan S. AIDS care. 2017 May 16:1-4. doi: 10.1080/09540121.2017.1327647. [Epub ahead of print]

A stubborn health challenge for learners in South African public schools concerns sexual and reproductive health and rights (SRHR). In 2015, the Department of Basic Education (DBE) proposed the provision of condoms and SRHR-services to learners in schools. This study aimed to contribute to the finalisation and implementation of DBE's policy by exploring learners' perspectives on the provision of condoms and SRHR-services in schools. Sixteen focus group discussions were conducted with learners (n = 116) from 33 public schools, to assess their attitudes, social influences, and needs and desires regarding condom provision and SRHR-services in schools. The majority of learners did not support condom provision in schools as they feared that it may increase sexual activity. Contrarily, they supported the provision of other SRHR-services as clinics fail to offer youth-friendly services. Learners' sexual behaviour and access to SRHR-services are strongly determined by their social environment, including traditional norms and values, and social-pressure from peers and adults. Learners' most pressing needs and desires to access condoms and SRHR-services in school concerned respect, privacy and confidentiality of such service provision. Implementation of DBE's policy must be preceded by an evidence-informed advocacy campaign to debunk myths about the risk of increased sexual activity, to advocate for why such services are needed, to shift societal norms towards open discussion of adolescent SRHR and to grapple with the juxtaposition of being legally empowered but socially inhibited to protect oneself from HIV, STIs and early pregnancy. Provision of condoms and other SRHR-services in schools must be sensitive to learners' privacy and confidentiality to minimise stigma and discrimination.

Abstract  Full-text [free] access

Impact of insurance coverage on utilization of pre-exposure prophylaxis for HIV prevention

Patel RR, Mena L, Nunn A, McBride T, Harrison LC, Oldenburg CE, Liu J, Mayer KH, Chan PA.  PLoS One. 2017 May 30;12(5):e0178737 . doi: 10.1371/journal.pone.0178737. eCollection 2017.

Pre-exposure prophylaxis (PrEP) can reduce U.S. HIV incidence. We assessed insurance coverage and its association with PrEP utilization. We reviewed patient data at three PrEP clinics (Jackson, Mississippi; St. Louis, Missouri; Providence, Rhode Island) from 2014-2015. The outcome, PrEP utilization, was defined as patient PrEP use at three months. Multivariable logistic regression was performed to determine the association between insurance coverage and PrEP utilization. Of 201 patients (Jackson: 34%; St. Louis: 28%; Providence: 28%), 91% were male, 51% were White, median age was 29 years, and 21% were uninsured; 82% of patients reported taking PrEP at three months. Insurance coverage was significantly associated with PrEP utilization. After adjusting for Medicaid-expansion and individual socio-demographics, insured patients were four times as likely to use PrEP services compared to the uninsured (OR: 4.49, 95% CI: 1.68-12.01; p = 0.003). Disparities in insurance coverage are important considerations in implementation programs and may impede PrEP utilization.

Abstract  Full-text [free] access

Medication adherence, condom use and sexually transmitted infections in Australian PrEP users: interim results from the Victorian PrEP demonstration project

Lal L, Audsley J, Murphy D, Fairley CK, Stoove M, Roth N, Moore R, Tee BK, Puratmaja N, Anderson PL, Leslie D, Grant RM, De Wit J, Wright E; VicPrEP Study Team. AIDS. 2017 May 1 doi: 10.1097/QAD.0000000000001519. [Epub ahead of print]

Objective: HIV Pre-exposure prophylaxis (PrEP) decreases risk of HIV acquisition however its efficacy is closely dependent on adherence. There is also concern that the preventive effect of PrEP may be offset by risk compensation, notably an increase in condomless anal sex.

Design: Multi-site, open-label demonstration study that recruited people at current or recent risk of HIV infection in Melbourne, Australia.

Methods: Participants were recruited from three general practice clinics and one sexual health clinic in Melbourne and consented to take daily tenofovir/emtricitabine for 30 months. Sexual practice data, HIV and sexually transmitted infection (STI) test results were collected at baseline and 3-monthly during follow up. PrEP adherence was evaluated by self-report at clinical visits, online surveys, refill-based assessments and dried blood spot (DBS) testing. We present a 12-month interim analysis.

Results: 114 people were recruited. We observed a significant decline in condom use which occurred concomitantly with a significant increase in STIs over the first 12 months of PrEP. Incidence (per 100PY) of any STI was 43.2 and 119.8 at m0-3 and M3-12, respectively (IRR 2.77 (1.52, 5.56)). Adherence to PrEP medication was high by all measures, including six month TDF-FTC levels in DBS.

Conclusions: We found significant reduction in condom use and an increase STIs over the first 12 months of follow-up. High medication adherence rates coupled with a decline in condom use and a rise in STIs, suggests that prevention, early detection and treatment of STIs is a chief research priority in the current era of HIV PrEP.

Abstract

Men who have sex with men starting pre-exposure prophylaxis (PrEP) are at risk of HCV infection: evidence from the Amsterdam PrEP study

Hoornenborg E, Achterbergh RC, Van Der Loeff MF, Davidovich U, Hogewoning A, de Vries HJ, Schinkel J, Prins M, Laar TJWV; Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative, MOSAIC study group. AIDS. 2017 May 1. doi: 10.1097/QAD.0000000000001522. [Epub ahead of print].

Objectives and Design: Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start pre-exposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM.

Methods: At enrolment in the Amsterdam PrEP (AMPrEP) demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis.

Results: Of 375 HIV-negative MSM enrolled in AMPrEP, 18 (4.8%, 95%CI 2.9%-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15/18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%) and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV.

Conclusion: HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.

Abstract

Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial.

Markowitz M, Frank I, Grant RM, Mayer KH, Elion R, Goldstein D, Fisher C, Sobieszczyk ME, Gallant JE, Van Tieu H, Weinberg W, . Margolis DA, Hudson KJ, Stancil BS, Ford SL, Patel P, Gould E, Rinehart AR, Smith KY, Spreen WR. Lancet HIV. 2017 May 22. pii: S2352-3018(17)30068-1. doi: 10.1016/S2352-3018(17)30068-1. [Epub ahead of print]

Background: Cabotegravir (GSK1265744) is an HIV-1 integrase strand transfer inhibitor with potent antiviral activity and a long half-life when administered by injection that prevented simian-HIV infection upon repeat intrarectal challenge in male macaques. We aimed to assess the safety, tolerability, and pharmacokinetics of long-acting cabotegravir injections in healthy men not at high risk of HIV-1 infection.

Methods: We did this multicentre, double-blind, randomised, placebo-controlled, phase 2a trial at ten sites in the USA. Healthy men (aged 18-65 years) deemed not at high risk of acquiring HIV-1 at screening were randomly assigned (5:1), via computer-generated central randomisation schedules, to receive cabotegravir or placebo. Participants received oral cabotegravir 30 mg tablets or matching placebo once daily during a 4 week oral lead-in phase, followed by a 1 week washout period and, after safety assessment, three intramuscular injections of long-acting cabotegravir 800 mg or saline placebo at 12 week intervals. Study site staff and participants were masked to treatment assignment from enrolment through week 41 (time of the last injection). The primary endpoint was safety and tolerability from the first injection (week 5) to 12 weeks after the last injection. We did analysis in the safety population, defined as all individuals enrolled in the study who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov identifier, NCT02076178.

Findings: Between March 27, 2014, and Feb 23, 2016, we randomly assigned 127 participants to receive cabotegravir (n=106) or placebo (n=21); 126 (99%) participants comprised the safety population. Most participants were men who have sex with men (MSM; n=106 [83%]) and white (n=71 [56%]). 87 (82%) participants in the cabotegravir group and 20 (95%) participants in the placebo group completed the injection phase. Adverse events (n=7 [7%]) and injection intolerability (n=4 [4%]) were the main reasons for withdrawal in the cabotegravir group. The frequency of grade 2 or higher adverse events was higher in participants in the long-acting cabotegravir group (n=75 [80%]) than in those in the placebo group (n=10 [48%]; p=0·0049), mostly due to injection-site pain (n=55 [59%]). No significant differences were noted in concomitant medications, laboratory abnormalities, electrocardiogram, and vital sign assessments. Geometric mean trough plasma concentrations were 0·302 μg/mL (95% CI 0·237-0·385), 0·331 μg/mL (0·253-0·435), and 0·387 μg/mL (0·296-0·505) for injections one, two, and three, respectively, indicating lower than predicted exposure. The geometric mean apparent terminal phase half-life estimated after the third injection was 40 days. Two (2%) MSM acquired HIV-1 infection, one in the placebo group during the injection phase and one in the cabotegravir group 24 weeks after the final injection when cabotegravir exposure was well below the protein-binding-adjusted 90% inhibitory concentration.

Interpretation: Despite high incidence of transient, mild-to-moderate injection-site reactions, long-acting cabotegravir was well tolerated with an acceptable safety profile. Pharmacokinetic data suggest that 800 mg administered every 12 weeks is a suboptimal regimen; alternative dosing strategies are being investigated. Our findings support further investigation of long-acting injectable cabotegravir as an alternative to orally administered pre-exposure prophylaxis regimens.

Abstract

Examination of HIV infection through heterosexual contact with partners who are known to be HIV infected in the United States, 2010-2015

Crepaz N, Dong B, Chen M, Hall I. AIDS. 2017 Jul 17;31(11):1641-1644. doi: 10.1097/QAD.0000000000001526.

Using data from the National HIV Surveillance System, we examined HIV infections diagnosed between 2010 and 2015 attributed to heterosexual contact with partners previously known to be HIV infected. More than four in 10 HIV infections among heterosexual males and five in 10 HIV infections among heterosexual women were attributed to this group. Findings may inform the prioritization of prevention and care efforts and resource allocation modeling for reducing new HIV infection among discordant partnerships.

Abstract

A national study of the molecular epidemiology of HIV-1 in Australia 2005–2012

Castley A, Sawleshwarkar S, Varma R, Herring B, Thapa K, Dwyer D, Chibo D, Nguyen N, Hawke K, Ratcliff R, Garsia R, Kelleher A, Nolan D; Australian Molecular Epidemiology Network-HIV (AMEN-HIV).. PLoS One. 2017 May 10;12(5):e0170601. doi: 10.1371/journal.pone.0170601. eCollection 2017.

Introduction: Rates of new HIV-1 diagnoses are increasing in Australia, with evidence of an increasing proportion of non-B HIV-1 subtypes reflecting a growing impact of migration and travel. The present study aims to define HIV-1 subtype diversity patterns and investigate possible HIV-1 transmission networks within Australia.

Methods: The Australian Molecular Epidemiology Network (AMEN) HIV collaborating sites in Western Australia, South Australia, Victoria, Queensland and western Sydney (New South Wales), provided baseline HIV-1 partial pol sequence, age and gender information for 4873 patients who had genotypes performed during 2005-2012. HIV-1 phylogenetic analyses utilised MEGA V6, with a stringent classification of transmission pairs or clusters (bootstrap ≥98%, genetic distance ≤1.5% from at least one other sequence in the cluster).

Results: HIV-1 subtype B represented 74.5% of the 4873 sequences (WA 59%, SA 68.4%, w-Syd 73.8%, Vic 75.6%, Qld 82.1%), with similar proportion of transmission pairs and clusters found in the B and non-B cohorts (23% vs 24.5% of sequences, p = 0.3). Significantly more subtype B clusters were comprised of ≥3 sequences compared with non-B clusters (45.0% vs 24.0%, p = 0.021) and significantly more subtype B pairs and clusters were male-only (88% compared to 53% CRF01_AE and 17% subtype C clusters). Factors associated with being in a cluster of any size included; being sequenced in a more recent time period (p<0.001), being younger (p<0.001), being male (p = 0.023) and having a B subtype (p = 0.02). Being in a larger cluster (>3) was associated with being sequenced in a more recent time period (p = 0.05) and being male (p = 0.008).

Conclusion: This nationwide HIV-1 study of 4873 patient sequences highlights the increased diversity of HIV-1 subtypes within the Australian epidemic, as well as differences in transmission networks associated with these HIV-1 subtypes. These findings provide epidemiological insights not readily available using standard surveillance methods and can inform the development of effective public health strategies in the current paradigm of HIV prevention in Australia

Abstract  Full-text [free] access

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

Ratmann O, Wymant C, Colijn C, Danaviah S, Essex M, Frost SD, Gall A, Gaiseitsiwe S, Grabowski M, Gray R, Guindon S, von Haeseler A, Kaleebu P, Kendall M, Kozlov A, Manasa J, Minh BQ, Moyo S, Novitsky V, Nsubuga R, Pillay S, Quinn TC, Serwadda D, Ssemwanga D, Stamatakis A, Trifinopoulos J, Wawer M, Leigh Brown A, de Oliveira T, Kellam P, Pillay D, Fraser C.. AIDS Res Hum Retroviruses. 2017 May 25. doi: 10.1089/AID.2017.0061. [Epub ahead of print].

To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3' end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

Abstract  Full-text [free] access

 

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Key populations need so much more than HIV-specific services – involve them at every stage of planning and programming

Editor’s notes: This month sees a welcome set of papers covering female sex workers in West Africa; gay men and other men who have sex with men in the Middle East and in East Africa; people who inject drugs in the USA and eastern Europe.

Sex work is legal in Cote d’Ivoire although soliciting and pandering are criminalized, which creates legal barriers to practicing sex work.  Legalization does not necessarily prevent widespread abuse of power. Lyons and colleagues recruited 466 female sex workers in Abidjan through a respondent driven sampling approach.  A structured interview and rapid HIV test was performed.  Around 11% of the women were found to be living with HIV and it is clear that there are large unmet needs for HIV-specific services.  Only one quarter of those living with HIV reported that they knew their status and of these, only a few were already taking ART.  However, the focus of this study was on violence, both physical and sexual, which was alarmingly common, with around 54% of women reporting physical violence and 43% sexual violence.  The violence was most often perpetrated by spouses and boyfriends as well as by paying customers.  Other sex workers, pimps or managers and uniformed officers were also responsible for violence, both physical and sexual.  16% of women said that they had been tortured.  Collecting reliable data on sensitive areas with vulnerable populations is challenging.  The sampling method may introduce biases, and the interviews may lead to reported behaviours to “please” the interviewer.  However, this study included major efforts to work with the community of sex workers and their networks, and considerable trust has been built, so the results seem credible.  The authors call for structural interventions and policy reforms that have little to do with HIV directly, but would lead to an environment where HIV and other harms were greatly reduced.  There is also a direct need to ensure that sex workers have good access to HIV and other sexual and reproductive health services.

People who inject drugs also have many needs besides HIV services.  In the USA, the number of people who inject drugs is increasing.  This has led to a rising number of deaths from opioid overdose (around 30 000 in 2014), as well as increased HIV transmission, which makes the headlines of the news, when it occurs in settings where HIV is otherwise rare.  Cost-effective HIV prevention programmes for people who inject drugs are essential to the long-term health outcomes for this population and other high-risk groups in the USA.  Bernard and colleagues used a mathematical model and economic analysis to identify the most cost-effective interventions for HIV prevention programmes for people who inject drugs in the USA.

The authors found that under many likely assumptions about potential scale up, the best buy was always to provide opioid agonist therapy, which reduces injecting frequency and results in multiple, immediate quality-of-life improvements.  Needle and syringe exchange programmes are less expensive, but in these models produced fewer benefits, making them the next most cost-effective intervention, alone or in combination. PrEP was not likely to be cost-effective in this population except in the very highest risk settings.  This is in line with the values and preference expressed by many people who use drugs around the world.  The priority should be for “standard” harm reduction approaches, which will reduce HIV transmission, but have far wider benefits on the health and well-being of drug users and their communities.

Relatively little research is carried out with key populations in the Middle East.  Heimer and colleagues also used respondent driven sampling (with the same potential biases as above) to recruit 292 men who have sex with men in Beirut.  Although one quarter of the participants had been born in Syria and moved recently to Lebanon, the sampling method does reduce the precision of this estimate.  Of 36 people living with HIV identified, 32 were on HIV treatment, which is encouraging.  If the 32 on treatment were virally suppressed, the prevalence of “infectious HIV” in the survey was around 1.4%.  As we move forward into the viral load era, notions of risk for sexual behaviour will change, and we need to think about explicit descriptions such as “condomless sex” rather than simply referring to “unprotected sex”.  As stated above, the benefits of condoms for other sexually transmitted infections as well as for HIV need to be emphasized and the full range of ARV-based prevention made available in order to minimize the epidemic of HIV among gay men and other men who have sex with men in Lebanon and beyond.

The dynamics of the HIV epidemic in Ukraine are shifting.  Increasingly sexual transmission is becoming more common, and transmission through injecting drug use reducing.  Fearnhill and colleagues’ study of phylogenetics and recent infections among 876 newly diagnosed people living with HIV in Kiev highlights these trends.  The study also demonstrates plenty of uncertainty and suggests that the stigma associated with both injecting drug use and with gay men and other men having sex with men may lead to significant under-reporting of both in traditional epidemiological surveillance.  Although phylogenetics cannot prove misclassification, it is highly suggestive when large clusters of HIV from known gay men and other men who have sex with men include no women, but do include other men, who self-report to be heterosexual.  Transmission was most common among gay men and other men who have sex with men, and from those with recent infections.  HIV strains from women often cluster with those from people who inject drugs.  In a complex and dynamic environment with overlapping risk factors for HIV infection, phylogenetics adds a useful lens through which to examine what is happening.  Yet again, the challenge is to translate more granular understanding of the epidemics into clear public health policy and practice.

What do men who have sex with men in Kenya think about participating in HIV prevention research, such as a vaccine trial?  Doshi and colleagues used a social network-based approach to conduct in-depth interviews with 70 gay men and other men who have sex with men.  Here is what some of them said:

“He [the potential study participant] keeps hearing there is a research [study] that is starting, that there is money – one thousand or two, three thousand – he will run for the money…because it is someone’s life you have to be sure of what is going on…. You run for the better option because research comes in every type and researchers are everywhere in town.”

“Ok, you know most of the research coming to Kenya starts with MSM. Those are the ones that are tested on first so if there are side effects, those will be the first victims”

“It will benefit many of us…on my side…because sometimes I’m drunk I go out and meet people and they tell me they do not use condom…or… I’m drunk, I don’t know myself and I have already come to the bed with someone. Even I don’t know what he will do to me, if he will do me with a condom or if he will do me without a condom. Now the [HIV] vaccine…will be beneficial to me and the whole community”

This is a rich paper, giving insights into the reasons that people do or do not want to participate in vaccine trials.  It raises plenty of ethical questions about the balance between self-interest, altruism, coercion and consent.  It is encouraging that on the whole most participants saw the potential benefits to the wider community and would consider volunteering their time despite the associated risks.  Their perceptions were also coloured by previous research studies and how researchers had met their responsibilities for the care and well-being of their participants.  A good advertisement for the UNAIDS-AVAC Good Participatory Practice guidance!

Physical and sexual violence affecting female sex workers in Abidjan, Côte d'Ivoire: prevalence, and the relationship with the work environment, HIV, and access to health services

Lyons CE, Grosso A, Drame FM, Ketende S, Diouf D, Ba I, Shannon K, Ezouatchi R, Bamba A, Kouame A, Baral S. J Acquir Immune Defic Syndr. 2017 May 1;75(1):9-17. doi: 10.1097/QAI.0000000000001310.

Background: Violence is a human rights violation, and an important measure in understanding HIV among female sex workers (FSW). However, limited data exist regarding correlates of violence among FSW in Côte d'Ivoire. Characterizing prevalence and determinants of violence and the relationship with structural risks for HIV can inform development and implementation of comprehensive HIV prevention and treatment programs.

Methods: FSW > 18 years were recruited through respondent driven sampling (RDS) in Abidjan, Côte d'Ivoire. In total, 466 participants completed a socio-behavioral questionnaire and HIV testing. Prevalence estimates of violence were calculated using crude and RDS-adjusted estimates. Relationships between structural risk factors and violence were analyzed using χ2 tests and multivariable logistic regression.

Results: The prevalence of physical violence was 53.6% (250/466), and sexual violence was 43.2% (201/465) among FSW in this study. Police refusal of protection was associated with physical (adjusted Odds Ratio [aOR]: 2.8; 95% confidence interval [CI]: 1.7 to 4.4) and sexual violence (aOR: 3.0; 95% CI: 1.9 to 4.8). Blackmail was associated with physical (aOR: 2.5; 95% CI: 1.5 to 4.2) and sexual violence (aOR: 2.4; 95% CI: 1.5 to 4.0). Physical violence was associated with fear (aOR: 2.2; 95% CI: 1.3 to 3.1) and avoidance of seeking health services (aOR: 2.3; 95% CI: 1.5 to 3.8).

Conclusions: Violence is prevalent among FSW in Abidjan and associated with features of the work environment and access to care. These relationships highlight layers of rights violations affecting FSW, underscoring the need for structural interventions and policy reforms to improve work environments, and to address police harassment, stigma, and rights violations to reduce violence and improve access to HIV interventions.

Abstract

Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: a model-based analysis

Bernard CL, Owens DK, Goldhaber-Fiebert JD, Brandeau ML. PLoS Med. 2017 May 24;14(5):e1002312 doi: 10.1371/journal.pmed.1002312. eCollection 2017 May.

Background: The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID) a public health priority. Some of these programs have benefits beyond prevention of HIV-a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT), needle and syringe programs (NSPs), HIV testing and treatment (Test & Treat), and oral HIV pre-exposure prophylaxis (PrEP).

Methods and Findings: We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars), health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs) of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively) and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22 000 (95% CI: 5200, 46 000) infections and cost US$18 000 (95% CI: US$14 000, US$24 000) per QALY gained, 50% NSP coverage could avert up to 35 000 (95% CI: 8900, 43 000) infections and cost US$25 000 (95% CI: US$7000, US$76 000) per QALY gained, 50% Test & Treat coverage could avert up to 6700 (95% CI: 1200, 16 000) infections and cost US$27 000 (95% CI: US$15 000, US$48 000) per QALY gained, and 50% PrEP coverage could avert up to 37 000 (22 000, 58 000) infections and cost US$300 000 (95% CI: US$162 000, US$667 000) per QALY gained. When coverage expansions are allowed to include combined investment with other programs and are compared to the next best intervention, the model projects that scaling OAT coverage up to 50%, then scaling NSP coverage to 50%, then scaling Test & Treat coverage to 50% can be cost-effective, with each coverage expansion having the potential to cost less than US$50 000 per QALY gained relative to the next best portfolio. In probabilistic sensitivity analyses, 59% of portfolios prioritized the addition of OAT and 41% prioritized the addition of NSPs, while PrEP was not likely to be a priority nor a cost-effective addition. Our findings are intended to be illustrative, as data on achievable coverage are limited and, in practice, the expansion scenarios considered may exceed feasible levels. We assumed independence of interventions and constant returns to scale. Extensive sensitivity analyses allowed us to assess parameter sensitivity, but the use of a dynamic compartmental model limited the exploration of structural sensitivities.

Conclusions: We estimate that OAT, NSPs, and Test & Treat, implemented singly or in combination, have the potential to effectively and cost-effectively prevent HIV in US PWID. PrEP is not likely to be cost-effective in this population, based on the scenarios we evaluated. While local budgets or policy may constrain feasible coverage levels for the various interventions, our findings suggest that investments in combined prevention programs can substantially reduce HIV transmission and improve health outcomes among PWID.

Abstract  Full-text [free] access

HIV risk, prevalence, and access to care among men who have sex with men in Lebanon

Heimer R, Barbour R, Khoury D, Crawford FW, Shebl FM, Aaraj E, Khoshnood K. AIDS Res Hum Retroviruses. 2017 Jun 29 doi: 10.1089/AID.2016.0326. [Epub ahead of print].

Objective: Little is known about HIV prevalence and risk among men who have sex with men in much of the Middle East, including Lebanon. Recent national level surveillance has suggested an increase in HIV prevalence concentrated among men in Lebanon. We undertook a biobehavioral study to provide direct evidence for the spread of HIV.

Design: MSM were recruited by respondent driven sampling, interviewed, and offered HIV testing anonymously at sites located in Beirut, Lebanon from October 2014 through February 2015. The interview questionnaire was designed to obtain information on participants' sociodemographic situation, sexual behaviors, alcohol and drug use, health, HIV testing and care, experiences of stigma and discrimination. Individuals not reporting an HIV diagnosis were offered optional, anonymous HIV testing.

Results: Among the 292 MSM recruited, we identified 36 cases of HIV (12.3%). A quarter of the MSM were born in Syria and recently arrived in Lebanon. Condom use was uncommon; 65% reported unprotected sex with other men. Group sex encounters were reported by 22% of participants. Among the 32 individuals already aware of their infection, 30 were in treatment and receiving antiretroviral therapy.

Conclusions: HIV prevalence was substantially increased over past estimates. Efforts to control future increases will have to focus on reducing specific risk behaviors and experienced stigma and abuse, especially among Syrian refugees.

Abstract

A phylogenetic analysis of HIV-1 sequences in Kiev: findings among key populations

Fearnhill E, Gourlay A, Malyuta R, Simmons R, Ferns RB, Grant P, Nastouli E, Karnets I, Murphy G, Medoeva A, Kruglov Y, Yurchenko A, Porter K; CASCADE Collaboration in EuroCoord. Clin Infec Dis 2017 May 29: doi: 10.1093/cid/cix499. [Epub ahead of print].

Background: The HIV epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission.

Methods: Protease and RT sequences from 876 new HIV diagnoses (April 2013 - March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥ 2 sequences, ≥ 80% local branch support and maximum genetic distance of all sequence pairs in the cluster ≤ 2.5%. Recent infection was determined through the LAg avidity EIA assay. Sequences were analysed for transmitted drug resistance (TDR) mutations.

Results: 30% of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (OR 4.38 [95% CI 2.56-7.50]), risk group (OR 5.65 [3.27-9.75]) for men who have sex with men compared to heterosexual males, recent, compared to long-standing, infection (OR 2.72 [1.64-4.52]), reported sex work contact (OR 1.93 [1.07-3.47]) and younger age groups compared to age ≥36 (OR 1.83 [1.10-3.05] for age ≤25). Females were associated with lower odds of clustering than heterosexual males (OR 0.49 [0.31-0.77]). In multivariate analysis, risk group, subtype and age group were independently associated with clustering (p<0.001, p=0.007 and p=0.033). 18 sequences (2.1%) indicated evidence of TDR.

Conclusions: Our findings suggest high levels of transmission and bridging between risk groups.

Abstract  Full-text [free] access

Contextualizing willingness to participate: recommendations for engagement, recruitment & enrolment of Kenyan MSM in future HIV prevention trials

Doshi M, Avery L, Kaddu RP, Gichuhi M, Gakii G, du Plessis E, Dutta S, Khan S, Kimani J, Lorway RR. BMC Public Health. 2017 May 18;17(1):469 doi: 10.1186/s12889-017-4395-4.

Background: The HIV epidemic among men who have sex with men (MSM) continues to expand globally. The addition of an efficacious, prophylactic vaccine to combination prevention offers immense hope, particularly in low- and middle- income countries which bear the greatest global impact. However, in these settings, there is a paucity of vaccine preparedness studies that specifically pertain to MSM. Our study is the first vaccine preparedness study among MSM and female sex workers (FSWs) in Kenya. In this paper, we explore willingness of Kenyan MSM to participate in HIV vaccine efficacy trials. In addition to individual and socio-cultural motivators and barriers that influence willingness to participate (WTP), we explore the associations or linkages that participants draw between their experiences with or knowledge of medical research both generally and within the context of HIV/AIDS, their perceptions of a future HIV vaccine and their willingness to participate in HIV vaccine trials.

Methods: Using a social network-based approach, we employed snowball sampling to recruit MSM into the study from Kisumu, Mombasa, and Nairobi. A field team consisting of seven community researchers conducted in-depth interviews with a total of 70 study participants. A coding scheme for transcribed and translated data was developed and the data was then analysed thematically.

Results: Most participants felt that an HIV vaccine would bring a number of benefits to self, as well as to MSM communities, including quelling personal fears related to HIV acquisition and reducing/eliminating stigma and discrimination shouldered by their community. Willingness to participate in HIV vaccine efficacy trials was highly motivated by various forms of altruism. Specific researcher responsibilities centred on safe-guarding the rights and well-being of participants were also found to govern WTP, as were reflections on the acceptability of a future preventive HIV vaccine.

Conclusion: Strategies for engagement of communities and recruitment of trial volunteers for HIV vaccine efficacy trials should not only be grounded in and informed by investigations into individual and socio-cultural factors that impact WTP, but also by explorations of participants' existing experiences with or knowledge of medical research as well as attitudes and acceptance towards a future HIV vaccine.

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Africa, Asia, Northern America
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How do we know which activities make a difference to HIV prevention?

Editor’s notes: In order to be fairly certain that an intervention is responsible for changes in HIV or HIV-related behaviours, the gold standard is randomization. This allows for fair comparisons between groups, since factors that might alter the outcomes will be more or less equally balanced between the study groups.  This is true whether such confounding factors are expected, but also importantly, even those factors that are unknown, unexpected and unmeasured will also be balanced between the arms. 

A second key determinant of high quality research is to use an approach that maximizes full engagement and follow-up of participants in the study.  One such approach that is widely recognized is to use Good Participatory Practice.  

Rhodes and colleagues study condom promotion and HIV testing among the Hispanic/Latino community of gay men and other men who have sex with men in North Carolina, USA.  Although gay men and other men who have sex with men represent approximately 4% of the adult male population in the United States of America, they account for more than 80% of new HIV infections among men.  Around one quarter of gay men and other men who have sex with men are Hispanic or Latino.  The authors therefore wanted to use research to make a difference to the HIV burden of the Hispanic/Latino gay men and other men who have sex with men community in North Carolina, USA.  They found that despite the impact of HIV on Hispanic/ Latino gay men and other men who have sex with men, they were only able to identify one evidence-based behavioural HIV prevention programme focussed on this population.

The authors used an extensive community based participatory research partnership, whose members represented the Hispanic/ Latino gay men and other men who have sex with men community, AIDS service organizations, Hispanic/Latino-serving community organizations, and universities to develop, implement, and evaluate a Spanish-language, small group intervention designed to increase condom use and HIV testing among Hispanic/Latino gay men and other men who have sex with men (HOLA en Grupos).

304 participants were randomly allocated to the HOLA en Grupos intervention, or to a general health education comparison intervention having the same number of sessions (4) and duration (16 hours in total) that focussed on prostate, lung, and colorectal cancers; diabetes; high cholesterol; cardiovascular disease; and alcohol misuse. These topics for the control group were identified on the basis of identified needs and priorities of Hispanic/Latino gay men and other men who have sex with men.

HOLA en Grupos is grounded on social cognitive theory, empowerment education, and traditional Hispanic/Latino cultural values and includes four interactive modules of four hours each delivered in groups.  Participants in both intervention and control arms received reimbursement for their time, certificates of completion and meals and a celebration at the completion of the course.  In other words this was an intensive intervention that might be hard to replicate in most settings, but it follows very high standards both for developing and conducting the research and also for determining the impact of the intervention.

The intervention was associated with a large effect on both condom usage (four-fold higher in the intervention arm than the control) and HIV test uptake (an astonishing 14-fold higher, reflecting the relatively low testing rate in the control group).

A major limitation in many HIV prevention studies, including this one, is that the outcome is based on reported behaviour.  The challenge is that the real outcome of interest, which is new HIV infections, is relatively rare in almost all communities so that studies have to be huge and expensive, and the large majority of participants in both intervention and control arms do not in fact acquire HIV.  This is in contrast to most studies of treatment, where there are clearly defined biological, standardized measures which many or all participants are likely to reach.  Nonetheless, there are many examples of studies that find changes in reported behaviour that are not associated with biological markers of such change (such as incidence of HIV or other sexually transmitted infections, or pregnancy). 

There are also many observational or ecological studies that report changes in new HIV infections but that cannot truly say why the number of infections fell and whether the interventions used in the study were responsible for the changes.  For example Nwokolo and colleagues report in a short research letter on the dramatic decline in new HIV diagnoses in the large London clinic where they work.  New infections in that clinic, and in fact in other large clinics in London, have dropped by a remarkable 40% from 2015 to 2016, as originally reported in the popular science press before any scientific publication or presentation. The authors of the research letter are suitably cautious about how to account for the impressive decline.  Various systems have been improved over the past few years in this clinic to make it easier to have an HIV test and start treatment immediately.  However, most of the clinic team (and many other commentators) assume that it is also due to the rapid rise in the use of PrEP.  Although it is still not available through the UK National Health Service, the clinic has been at the forefront of encouraging gay men and other men who have sex with men who might benefit from PrEP to purchase it from on-line pharmacies.  The clinic then provides the appropriate monitoring and follow up to ensure that their clients get the best possible PrEP service given the current constraints.  Whatever the cause, we should be celebrating the rapid fall in new HIV infections across London, which is home to a substantial proportion of the new HIV infections in the UK.

The challenges of demonstrating evidence of effectiveness for HIV prevention is also felt among black women in the USA.  Although they have the highest burden of HIV among women in the USA, the incidence rates are such that a traditional randomized trial design would need to be huge, and consequently hugely expensive.  Adimora and colleagues consider whether an alternative trial design might be to use data from high HIV incidence settings and then to develop proxies of protection, such as the concentration of a PrEP medicine to infer whether black women are protected.  An alternative that has been proposed for men who have sex with men would be to look for other markers of high risk, such as sexually transmitted infections, reported partners, age, and substance use and estimate the likely risk of HIV acquisition in the absence of PrEP from these parameters.  Then the observed incidence could be compared to this modelled counterfactual, much as was done in the open label extension of the Partners PrEP study in Kenyan and Ugandan sero-different couples.  However, translating risk factors for infection across populations, and even continents when there is such heterogeneity in risk of infection is not at all straightforward.  So there is still plenty to think about and no clear answers yet!

A useful addition to the tool box for designing studies and assessing the effectiveness of interventions, would be better tools for measuring recent infection.  There are several assays all with differing characteristics but increasingly these differences and how they interact with different clades of HIV are becoming clear.  Key determinants for each assay are the mean duration of recent infection (MDRI) estimate (which does seem to vary by clade) and the false recency rate (FRR) which needs to be less than 2% to be considered useful.  Hargrove and colleagues used three different assays to test samples from 101 women who seroconverted during the ZVITAMBO trial.  The MDRI measured using standard cut-off points, were considerably shorter than those published for the general population.  The authors point out that changes in antibody properties among women who have recently given birth or other unspecified physiological states, mean that incidence assays may give different results from those published and expected.  Yet more caution when comparing incidence estimates between studies.  As an endpoint in a comparison between two groups in the same population, the assays are still attractive. Although, given typical MDRIs of around six to nine months, these assays will still need to be embedded in very large samples to give reliable estimates of incidence and statistically significant differences between groups.

This month saw the production of a useful supplement on many aspects of how data from different sources, including incidence assays are used to inform the sophisticated models on which so much HIV planning, programming and financing is based.  An example is Mahiane and colleagues’ paper on the development of a new tool to fit existing programme data into the spectrum suite of models in order to estimate incidence.

Finally in this section, for those who are keen on laboratory studies, Richardson-Harman and colleagues describe the current state of ex-vivo challenge models for assessing potential candidates as microbicides.  In these models, biopsies of rectal, cervical or vaginal tissue, taken during other procedures, or from volunteers, are kept alive in the laboratory.  The tissues can then be challenged with HIV in the presence or absence of potential microbicide products.  The current model works best for rectal tissues, in which infection occurs promptly and consistently, so that the effect of a microbicide can clearly be seen by a reduction in the production of HIV p24 antigen.  However, for cervical and vaginal tissues, the infection (in the absence of any microbicide) was less consistent, slower and lasted longer making it less easy to determine statistical differences between those tissues with microbicide and those without.  Further work of this sort may help to streamline the choice of microbicide or PrEP products that can most sensibly be taken out of the laboratory and into the (almost) real world of clinical trials.

Small-group randomized controlled trial to increase condom use and HIV testing among Hispanic/Latino gay, bisexual, and other men who have sex with men.

Rhodes SD, Alonzo J, Mann L, Song EY, Tanner AE, Arellano JE, Rodriguez-Celedon R, Garcia M, Freeman A, Reboussin BA, Painter TM. Am J Public Health. 2017 Jun;107(6):969-976. doi: 10.2105/AJPH.2017.303814. Epub 2017 Apr 20.

Objectives: To evaluate the HOLA en Grupos intervention, a Spanish-language small-group behavioral HIV prevention intervention designed to increase condom use and HIV testing among Hispanic/Latino gay, bisexual, and other men who have sex with men.

Methods: In 2012 to 2015, we recruited and randomized 304 Hispanic/Latino men who have sex with men, aged 18 to 55 years in North Carolina, to the 4-session HOLA en Grupos intervention or an attention-equivalent general health education comparison intervention. Participants completed structured assessments at baseline and 6-month follow-up. Follow-up retention was 100%.

Results: At follow-up, relative to comparison participants, HOLA en Grupos participants reported increased consistent condom use during the past 3 months (adjusted odds ratio [AOR] = 4.1; 95% confidence interval [CI] = 2.2, 7.9; P < .001) and HIV testing during the past 6 months (AOR = 13.8; 95% CI = 7.6, 25.3; P < .001). HOLA en Grupos participants also reported increased knowledge of HIV (P < .001) and sexually transmitted infections (P < .001); condom use skills (P < .001), self-efficacy (P < .001), expectancies (P < .001), and intentions (P < .001); sexual communication skills (P < .01); and decreased fatalism (P < .001).

Conclusions: The HOLA en Grupos intervention is efficacious for reducing HIV risk behaviors among Hispanic/Latino men who have sex with men.

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Not just PrEP: other reasons for London's HIV decline.

Nwokolo N, Whitlock G, McOwan A. Lancet HIV. 2017 Apr;4(4):e153. doi: 10.1016/S2352-3018(17)30044-9.

The reduction in HIV diagnoses in London in 2016 is attributed to pre-exposure prophylaxis (PrEP). We believe that the causes of the 42% decline seen at our clinic are likely to be multifactorial. 56 Dean Street diagnoses one in four of London's HIV cases, 50% of whom have incident infection (ie, within 4 months of infection). Because of this, and following the results of the START study, we actively recommend treatment at, or close to, diagnosis, reducing the risk of transmission in people who would otherwise be highly infectious.

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US black women and HIV prevention: time for new approaches to clinical trials.

Adimora AA, Cole SR, Eron JJ Clin Infect Dis. 2017 Apr 5. doi: 10.1093/cid/cix313. [Epub ahead of print]. 

Black women bear the highest burden of HIV infection among US women. Tenofovir/ emtricitabine HIV prevention trials among women in Africa have yielded varying results. Ideally, a randomized controlled trial (RCT) among US women would provide data for guidelines for US women's HIV pre-exposure prophylaxis use. However, even among US black women at high risk for HIV infection, sample size requirements for an RCT with HIV incidence as its outcome are prohibitively high. We propose to circumvent this large sample size requirement by evaluating relationships between HIV incidence and drug concentrations measured among participants in traditional phase 3 trials in high incidence settings - and then applying these observations to drug concentrations measured among at risk individuals in lower incidence settings, such as US black women. This strategy could strengthen the evidence base to enable black women to fully benefit from prevention research advances and decrease racial disparities in HIV rates.

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Heightened HIV antibody responses in postpartum women as exemplified by recent infection assays: implications for incidence estimates.

Hargrove JW, van Schalkwyk C, Humphrey JH, Mutasa K, Ntozini R, Owen SM, Masciotra S, Parekh BS, Duong YT, Dobbs T, Kilmarx PH, Gonese E. AIDS Res Hum Retroviruses. 2017 May 24. doi: 10.1089/AID.2016.0319. [Epub ahead of print].

Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations, and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. We determined MDRIs for multi-subtype peptide representing subtypes B, E and D (BED)-capture enzyme immunoassay, limiting antigen (LAg), and Bio-Rad Avidity Incidence (BRAI) assays for 101 seroconverting postpartum women, recruited in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers and Babies trial, comparing them against published MDRIs estimated from seroconverting cases in the general population. We also compared MDRIs for women who seroconverted either during the first 9 months, or at later stages, postpartum. At cutoffs (C) of 0.8 for BED, 1.5 for LAg, and 40% for BRAI, estimated MDRIs for postpartum mothers were 192, 104, and 144 days, 33%, 32%, and 52% lower than published estimates of 287, 152 and 298 days, respectively, for clade C samples from general populations. Point estimates of MDRI values were 7%-19% shorter for women who seroconverted in the first 9 months postpartum than for those seroconverting later. MDRI values for three HIV incidence biomarkers are longer in the general population than among postpartum women, particularly those who recently gave birth, consistent with heightened immunological activation soon after birth. Our results provide a caution that MDRI may vary significantly between subjects in different physiological states.

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Improvements in Spectrum's fit to program data tool.

Mahiane SG, Marsh K, Grantham K, Crichlow S, Caceres K, Stover J.  AIDS. 2017 Apr;31 Suppl 1:S23-S30. doi: 10.1097/QAD.0000000000001359.

Objective: The Joint United Nations Program on HIV/AIDS-supported Spectrum software package (Glastonbury, Connecticut, USA) is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with program and vital registration data, such as historical trends in the number of newly diagnosed infections or people living with HIV and AIDS related deaths. This article describes development and application of the fit to program data (FPD) tool in Joint United Nations Program on HIV/AIDS' 2016 estimates round.

Methods: In the FPD tool, HIV incidence trends are described as a simple or double logistic function. Function parameters are estimated from historical program data on newly reported HIV cases, people living with HIV or AIDS-related deaths. Inputs can be adjusted for proportions undiagnosed or misclassified deaths. Maximum likelihood estimation or minimum chi-squared distance methods are used to identify the best fitting curve. Asymptotic properties of the estimators from these fits are used to estimate uncertainty.

Results: The FPD tool was used to fit incidence for 62 countries in 2016. Maximum likelihood and minimum chi-squared distance methods gave similar results. A double logistic curve adequately described observed trends in all but four countries where a simple logistic curve performed better.

Conclusion: Robust HIV-related program and vital registration data are routinely available in many middle-income and high-income countries, whereas HIV seroprevalence surveillance and survey data may be scarce. In these countries, the FPD tool offers a simpler, improved approach to estimating HIV incidence trends.

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Analytical advances in the ex vivo challenge efficacy assay.

Richardson-Harman N, Parody R, Anton P, McGowan I, Doncel G, Thurman AR, Herrera C, Kordy K, Fox J, Tanner K, Swartz G, Dezzutti CS. AIDS Res Hum Retroviruses. 2017 Apr;33(4):395-403. doi: 10.1089/AID.2016.0073. Epub 2016 Dec 16.

The ex vivo challenge assay is being increasingly used as an efficacy endpoint during early human clinical trials of HIV prevention treatments. There is no standard methodology for the ex vivo challenge assay, although the use of different data collection methods and analytical parameters may impact results and reduce the comparability of findings between trials. In this analysis, we describe the impact of data imputation methods, kit type, testing schedule and tissue type on variability, statistical power, and ex vivo HIV growth kinetics. Data were p24 antigen (pg/ml) measurements collected from clinical trials of candidate microbicides where rectal (n = 502), cervical (n = 88), and vaginal (n = 110) tissues were challenged with HIV-1BaL ex vivo. Imputation of missing data using a nonlinear mixed effect model was found to provide an improved fit compared to imputation using half the limit of detection. The rectal virus growth period was found to be earlier and of a relatively shorter duration than the growth period for cervical and vaginal tissue types. On average, only four rectal tissue challenge assays in each treatment and control group would be needed to find a one log difference in p24 to be significant (alpha = 0.05), but a larger sample size was predicted to be needed for either cervical (n = 21) or vaginal (n = 10) tissue comparisons. Overall, the results indicated that improvements could be made in the design and analysis of the ex vivo challenge assay to provide a more standardized and powerful assay to compare efficacy of microbicide products.

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