Articles tagged as "HIV This Month 2016 #01 - January 2016"

A pill for HIV prevention: to take when you need it

On-demand preexposure prophylaxis in men at high risk for HIV-1 infection.

Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, Tremblay C, Le Gall JM, Cua E, Pasquet A, Raffi F, Pintado C, Chidiac C, Chas J, Charbonneau P, Delaugerre C, Suzan-Monti M, Loze B, Fonsart J, Peytavin G, Cheret A, Timsit J, Girard G, Lorente N, Preau M, Rooney JF, Wainberg MA, Thompson D, Rozenbaum W, Dore V, Marchand L, Simon MC, Etien N, Aboulker JP, Meyer L, Delfraissy JF, Group AIS. N Engl J Med. 2015 Dec 3;373(23):2237-46. doi: 10.1056/NEJMoa1506273. Epub 2015 Dec 1.

Background: Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen.

Methods: We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections.

Results: Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03).

Conclusions: The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events.

Abstract Full-text [free] access

Editor’s notes: The IPERGAY trial is the first trial to assess ‘on demand’ HIV pre-exposure prophylaxis (PrEP). It had a ‘take it when you need it’ approach, rather than a daily dosing approach where a pill is taken every day, regardless of sexual activity. In 2010, the iPrEx Trial of daily pills among gay men and other men who have sex with men reported a 42% relative reduction in HIV incidence. In participants with detectable drug in their blood (meaning that they had been taking the pills), the reduction was 92%. The IPERGAY researchers set out to prove or disprove the hypothesis that men would be more likely to take pills if pill-taking was associated with having sex. The hypothesis was that this might improve adherence and hence reduce the risk of HIV acquisition compared with daily dosing. Participants were randomly assigned to take a dose of two pills of TDF/FTC (tenofovir disoproxil fumarate/emtricitabine) or placebo with food between two and 24 hours before sex. A third pill was taken 24 hours after sex and a fourth pill 24 hours after that. If they continued to be sexually active, they were told to take one pill a day while sexually active and then the two post-exposure doses 24 hours apart. When the striking results of the PROUD trial in the United Kingdom, among gay men and other men who have sex with men, were made public [see HIV This Month February 2015], IPERGAY’s Data Safety and Monitoring Board (DSMB) asked for an unblinded interim analysis of the IPERGAY data. The results were so convincing (an 86% relative risk reduction) that the DSMB recommended that the trial be unblinded so that men in the placebo arm could be offered active drug. The next question was whether this highly effective preventive measure could be made available outside the trial setting. The Food and Drug Administration of the United States of America had approved TDF/FTC for HIV PrEP in 2012 but no country had followed suit. On November 23, 2015, France’s Minister for Social Affairs, Health, and Women’s Rights announced a temporary recommendation for the use of TDF/FTC HIV prophylaxis, opening the way to the authorisation of PrEP in other European countries. Before any other European country responded, South Africa’s Medicines Control Council announced on December 3, 2015 its approval of the fixed-dose combination of TDF/FTC for pre-exposure prophylaxis of HIV. Kenya’s Pharmacy & Poisons Board also approved once-daily use of TDF/FTC for HIV prevention on December 23, 2015. The scientific evidence has been building for years. Clearly it is time to act now to make this highly effective HIV prevention choice available to people at highest risk of HIV exposure.

Europe, Northern America
Canada, France
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Long-acting PrEP might offer a solution to the challenges of adherence

Potential clinical and economic value of long-acting preexposure prophylaxis for South African women at high-risk for HIV infection.

Walensky RP, Jacobsen MM, Bekker LG, Parker RA, Wood R, Resch SC, Horstman NK, Freedberg KA, Paltiel AD. J Infect Dis. 2015 Dec 17. pii: jiv523. [Epub ahead of print]

Background: For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown.

Methods: Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact.

Results: Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women.

Conclusions: Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives.

Abstract  Full-text [free] access

Editor’s notes: Standard oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV and is one of the few proven prevention options available to young women at risk of HIV. However, daily adherence is key and trials have illustrated problems with adherence in several populations. Development of long-acting injectable formulations of PrEP may provide an option that does not require daily adherence to pills. In anticipation of new formulations of PrEP, this study modelled the potential clinical benefits, additional cost, cost-effectiveness and budget impact of existing and novel PrEP strategies. Given that the effectiveness and cost of long-acting PrEP is unknown, sensitivity analyses were conducted to look at varied effectiveness, HIV infection incidence, age at PrEP discontinuation and programmatic cost. The results suggest that long-acting PrEP is likely to be more clinically and cost-effective than standard oral PrEP. However, it will place an even greater strain on existing HIV prevention budgets. In addition to the research necessary to establish its clinical effectiveness, efforts to develop novel financing mechanisms are also required.         

Africa
South Africa
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Adolescents, safer sex and HIV-status disclosure in South Africa

Sex and secrecy: how HIV-status disclosure affects safe sex among HIV-positive adolescents.

Toska E, Cluver LD, Hodes R, Kidia KK. AIDS Care. 2015 Dec;27 Suppl 1:47-58. doi: 10.1080/09540121.2015.1071775.

HIV-positive adolescents who engage in unsafe sex are at heightened risk for transmitting or re-acquiring HIV. Disclosure of HIV-status to sexual partners may impact on condom use, but no study has explored the effects of (i) adolescent knowledge of one's HIV-status, (ii) knowledge of partner status and (iii) disclosure to partners, on safer sex behaviour. This study aimed to identify whether knowledge of HIV-status by HIV-positive adolescents and partners was associated with safer sex. Eight hundred and fifty eight HIV-positive adolescents (10-19 years old, 52% female, 68.1% vertically infected) who had ever initiated antiretroviral treatment in 41 health facilities in the Eastern Cape, South Africa, were interviewed using standardised questionnaires. Quantitative analyses used multivariate logistic regressions, controlling for confounders. Qualitative research included interviews, focus group discussions and observations with 43 HIV-positive teenagers and their healthcare workers. N = 128 (14.9%) of the total sample had ever had sex, while N = 109 (85.1%) of sexually active adolescents had boy/girlfriend. In total, 68.1% of the sample knew their status, 41.5% of those who were sexually active and in relationships knew their partner's status, and 35.5% had disclosed to their partners. For adolescents, knowing one's status was associated with safer sex (OR = 4.355, CI 1.085-17.474, p = .038). Neither knowing their partner's status, nor disclosing one's HIV-status to a partner, were associated with safer sex. HIV-positive adolescents feared rejection, stigma and public exposure if disclosing to sexual and romantic partners. Counselling by healthcare workers for HIV-positive adolescents focused on benefits of disclosure, but did not address the fears and risks associated with disclosure. These findings challenge assumptions that disclosure is automatically protective in sexual and romantic relationships for HIV-positive adolescents, who may be ill-equipped to negotiate safer sex. There is a pressing need for effective interventions that mitigate the risks of disclosure and provide HIV-positive adolescents with skills to engage in safe sex.

Abstract  Full-text [free] access

Editor’s notes: Ninety percent of the world’s adolescents living with HIV, live in sub-Saharan Africa.  Evidence illustrates high levels of condomless sex with other adolescents (27-90%) and low rates of disclosure to sexual partners. Negotiating safer sexual practices is particularly challenging for HIV-positive adolescents, exacerbated by HIV-associated factors, learning and accepting their status, and withholding or disclosing their HIV status to sexual partners. There is a dearth of evidence on associations between disclosure and negotiating safer sexual practices among adolescents. This study examines the extent to which disclosure to, and by, adolescents living with HIV is associated with safer sex.

This mixed-methods study employed an iterative approach whereby preliminary qualitative findings guided quantitative measures, particularly items on disclosure. Emerging quantitative findings framed the thematic focus of qualitative research. The study was conducted in the eastern Cape, South Africa. Some 858 adolescents aged 10-19 years were recruited for the quantitative arm of the study. Some 43 participants were included in the qualitative arm of the study. Data generation methods used were individual interviews, focus group discussions and direct observations.

The findings indicate that among adolescents living with HIV, knowledge of HIV-status was strongly associated with safer sex. Knowing one’s partner’s status or disclosing one’s status was not.  Qualitative findings suggest that fear of rejection, exposure, and stigma discouraged HIV-positive adolescents from disclosing to their partners as a strategy for negotiating safer sex. Disclosure counselling and support from healthcare professionals did not address these challenges. Guidelines on counselling HIV-positive adolescents should focus on promoting safer sex with all sexual partners as a first priority, rather than promoting disclosure to sexual partners. Disclosure counselling for HIV-positive adolescents could also be enhanced by improving patient confidentiality, addressing adolescent fears on the dangers of disclosure and by giving HIV-positive adolescents skills to negotiate safer sex.

Africa
South Africa
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Condomless sex + viral suppression = ‘safe(r)’ sex? Challenging the laws that criminalise HIV transmission

HIV transmission law in the age of treatment-as-prevention.

Haire B, Kaldor J. J Med Ethics. 2015 Dec;41(12):982-6. doi: 10.1136/medethics-2014-102122. Epub 2015 Sep 29.

Evidence that treating people with HIV early in infection prevents transmission to sexual partners has reframed HIV prevention paradigms. The resulting emphasis on HIV testing as part of prevention strategies has rekindled the debate as to whether laws that criminalise HIV transmission are counterproductive to the human rights-based public health response. It also raises normative questions about what constitutes 'safe(r) sex' if a person with HIV has undetectable viral load, which has significant implications for sexual practice and health promotion. This paper discusses a recent high-profile Australian case where HIV transmission or exposure has been prosecuted, and considers how the interpretation of law in these instances impacts on HIV prevention paradigms. In addition, we consider the implications of an evolving medical understanding of HIV transmission, and particularly the ability to determine infectiousness through viral load tests, for laws that relate to HIV exposure (as distinct from transmission) offences. We conclude that defensible laws must relate to appreciable risk. Given the evidence that the transmissibility of HIV is reduced to negligible level where viral load is suppressed, this needs to be recognised in the framing, implementation and enforcement of the law. In addition, normative concepts of 'safe(r) sex' need to be expanded to include sex that is 'protected' by means of the positive person being virally suppressed. In jurisdictions where use of a condom has previously mitigated the duty of the person with HIV to disclose to a partner, this might logically also apply to sex that is 'protected' by undetectable viral load.

Abstract access

Editor’s notes: The changing landscape of HIV treatment challenges assumptions about the HIV epidemic based on past knowledge and understanding. The authors of this paper set out why laws that criminalise HIV transmission may now need to change. This change is required because of the impact of antiretroviral therapy on the viral load of someone living with HIV and taking their treatment regularly. As the authors note ‘it is no longer reasonable to classify condomless sex as ‘unsafe’ if the partner with HIV has an undetectable viral load’ (p. 985).  What the authors do not discuss is whether someone on antiretroviral therapy does indeed have a suppressed viral load.  Indeed, whether the person’s viral load suppression may change between the act for which they are prosecuted, and the time of the prosecution, is not discussed. The viral load of someone living with HIV on treatment may not stay suppressed if there is a break in adherence. That said, this paper does very effectively highlight how the evolution of the HIV epidemic affects many areas of life and institutions; including laws that may be slow to adapt and change.

Oceania
Australia, New Zealand
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How gender norms and power may impact on the acceptability, access and adherence to microbicides

Optimizing HIV prevention for women: a review of evidence from microbicide studies and considerations for gender-sensitive microbicide introduction.

Doggett EG, Lanham M, Wilcher R, Gafos M, Karim QA, Heise L. J Int AIDS Soc. 2015 Dec 21;18(1):20536. doi: 10.7448/IAS.18.1.20536. eCollection 2015.

Introduction: Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women and girls at risk of acquiring HIV are also likely to affect their ability to use microbicides. Understanding how gendered norms and inequalities may pose obstacles to women's microbicide use is important to inform product design, microbicide trial implementation and eventually microbicide and other antiretroviral-based prevention programmes. We reviewed published vaginal microbicide studies to identify gender-related factors that are likely to affect microbicide acceptability, access and adherence. We make recommendations on product design, trial implementation, positioning, marketing and delivery of microbicides in a way that takes into account the gender-related norms and inequalities identified in the review.

Methods: We conducted PubMed searches for microbicide studies published in journals between 2000 and 2013. Search terms included trial names (e.g. "MDP301"), microbicide product names (e.g. "BufferGel"), researchers' names (e.g. "van der Straten") and other relevant terms (e.g. "microbicide"). We included microbicide clinical trials; surrogate studies in which a vaginal gel, ring or diaphragm was used without an active ingredient; and hypothetical studies in which no product was used. Social and behavioural studies implemented in conjunction with clinical trials and surrogate studies were also included. Although we recognize the importance of rectal microbicides to women, we did not include studies of rectal microbicides, as most of them focused on men who have sex with men. Using a standardized review template, three reviewers read the articles and looked for gender-related findings in key domains (e.g. product acceptability, sexual pleasure, partner communication, microbicide access and adherence).

Results and discussion: The gendered norms, roles and relations that will likely affect women's ability to access and use microbicides are related to two broad categories: norms regulating women's and men's sexuality and power dynamics within intimate relationships. Though norms about women's and men's sexuality vary among cultural contexts, women's sexual behaviour and pleasure are typically less socially acceptable and more restricted than men's. These norms drive the need for woman-initiated HIV prevention, but also have implications for microbicide acceptability and how they are likely to be used by women of different ages and relationship types. Women's limited power to negotiate the circumstances of their intimate relationships and sex lives will impact their ability to access and use microbicides. Men's role in women's effective microbicide use can range from opposition to non-interference to active support.

Conclusions: Identifying an effective microbicide that women can use consistently is vital to the future of HIV prevention for women. Once such a microbicide is identified and licensed, positioning, marketing and delivering microbicides in a way that takes into account the gendered norms and inequalities we have identified would help maximize access and adherence. It also has the potential to improve communication about sexuality, strengthen relationships between women and men and increase women's agency over their bodies and their health.

Abstract  Full-text [free] access

Editor’s notes: This paper presents a review of the evidence of microbicides research to understand gender-associated factors that could impact on acceptability, access and adherence. These gender norms include women and men’s sexual norms and power differentials in intimate partner relationships. This review included studies conducted between 2000 and 2013 and thus only includes papers on hypothetical research and clinical trials. While the studies were conducted in a variety of contexts the authors found a number of similar norms and power differentials.

In relation to sexual norms, the review revealed findings on sexual risk, sexual pleasure, and sexual preferences. In terms of sexual risk there were differing opinions across the studies of which women were most likely to need microbicides. Some studies suggested that microbicides should be focused on women in steady partnerships where condom negotiation is difficult, while others suggested focusing on key populations such as sex workers. Across many studies the potential for promoting sexual pleasure for both women and men emerged as an advantage of microbicides, and had an impact on acceptability. However, many of the studies highlighted how men’s sexual pleasure takes precedence. In relation to sexual preferences, the much touted idea that men prefer ‘dry’ or ‘tight’ sex was challenged by some of the studies, which found that the lubricating effect of the gel was acceptable.

The review also uncovered issues associated to power inequalities in intimate partner relationships, including power to control time of sex, male partner engagement and communication, and intimate-partner violence. Women reported in many studies their lack of power to control the timing of sex and this is seen as likely to impact on their ability to use coitally-dependant microbicides. However, there is some evidence that men supported women’s use of the gel, although this depended on the type of relationship. While microbicides have been promoted as products that women can use without a partner’s knowledge the review illustrated that women do prefer to communicate with their partners about their use and there is evidence of joint-decision making. Further, there was evidence of women experiencing intimate partner violence in relation to trial participation. There is also some evidence that women were less likely to discuss or use microbicides in violent relationships.

This highly comprehensive review concludes that while microbicides will not empower women they do have the potential to enhance women’s agency in relation to their health and sexuality and may improve communication in their relationships. However, the authors conclude that gender norms and power differentials may impact on acceptability, access and adherence.

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Predicting acute HIV infection in key populations

Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa.

Sanders EJ, Wahome E, Powers KA, Werner L, Fegan G, Lavreys L, Mapanje C, McClelland RS, Garrett N, Miller WC, Graham SM. AIDS. 2015 Dec;29 Suppl 3:S221-30. doi: 10.1097/QAD.0000000000000924.

Background: Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission.

Methods: We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site.

Results: We compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18-29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5-50% of participants, substantially decreasing the number needing testing.

Conclusion: Our targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI.

Abstract  Full-text [free] access

Editor’s notes: This analysis adds to the literature around the performance of risk score algorithms to guide testing for acute HIV infection (AHI). The four studies included in this analysis involved key populations in different African settings. In common with previous analyses, genital ulcer disease had by far the strongest association with AHI. The derived algorithm had modest accuracy overall and poor performance in South Africa, where symptoms and signs were particularly infrequent.

Most studies included in this analysis were cohort studies following key individuals. Whether or not algorithms based on recording of symptoms and signs during intensive follow-up for AHI can be translated for use in a real world situation of unselected people presenting for health care remains unproven. Ultimately, we really need evidence about the impact and cost-effectiveness of detecting AHI in different populations. This is in order to define the role of testing for AHI, and in particular whether rationalising testing with algorithms such as this is necessary (especially for key populations).   

Africa
Kenya, Malawi, South Africa
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Why get tested for HIV in Russia?

Motivators and barriers to HIV testing among street-based female sex workers in St. Petersburg, Russia.

King EJ, Maman S, Dudina VI, Moracco KE, Bowling JM. Glob Public Health. 2015 Dec 28:1-16. [Epub ahead of print]

Female sex workers are particularly susceptible to HIV-infection in Russia. However, a dearth of information exists on their utilisation of HIV services. A mixed-methods, cross-sectional study was conducted to examine motivators and barriers to HIV testing among street-based sex workers in St. Petersburg, Russia. The health belief model was the theoretical framework for the study. Twenty-nine sex workers participated in in-depth interviews, and 139 sex workers completed interviewer-administered surveys between February and September 2009. Barriers to getting an HIV test were fear of learning the results, worrying that other people would think they were sick, and the distance needed to travel to obtain services. Motivators for getting tested were protecting others from infection, wanting to know one's status and getting treatment if diagnosed. Logistic regression analysis demonstrated that knowing people living with HIV [aOR = 6.75, 95% CI (1.11, 41.10)] and length of time since start of injection drug use [aOR = 0.30, 95% CI (0.09, 0.97)] were significantly associated with recently getting tested. These results are important to consider when developing public health interventions to help female sex workers in Russia learn their HIV status and get linked to care and treatment services if needed.

Abstract access 

Editor’s notes: This paper summarises findings from a mixed-method study among a sample of female sex workers in St Petersburg, Russian Federation, the majority of whom also inject drugs. This is an important study, allowing the voices of a highly marginalised group to be heard and highlighting barriers and facilitators to HIV testing. Improving access to testing among this population is particularly important given the increased risk of HIV infection that they face. They are susceptible to HIV infection through both sexual and injecting transmission routes. The paper raises some important points such as the widespread misunderstanding about the severity of HIV in the absence of symptoms. HIV was not perceived to be a major problem among the population; there were more immediate problems associated with drug use and sex work. The necessity to travel for testing was seen as a barrier to HIV testing. For a population with multiple and complex health needs this is an acute problem given the vertical structure of the Russian health system. There is a lack of integration across sexual health, drug dependency and HIV and other infectious disease treatment services necessary for this population.  Many other structural barriers were reported to testing including  fear of being registered as having HIV, fear of stigma from friends and health care workers, fear of the unknown associated with infection and disease progression and uncertainty about availability of HIV treatment.  Concerns about treatment availability are particularly relevant since people who inject drugs are often denied HIV treatment in the Russian Federation while they continue to use drugs. This point is important in understanding the context in which HIV testing is accessed. Further discussion on what real benefits knowing your status brings weighed up against the disadvantages of knowing, warrants further discussion in the paper. We know that there is limited and often interrupted HIV treatment available and few ancillary services (such as opioid substitution therapy) to support maintenance of treatment.  We also know that there is much stigma associated with being HIV positive. People living with HIV experience frequent problems with employment and concerns about having children taken into care. All these problems are compounded if you use drugs or sell sex. In this context, the benefits of knowing your status is questionable and is bound to influence uptake of testing.

Asia, Europe
Russian Federation
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Large multi-centre study finds few differences between mortality in migrant and native populations in western Europe

Mortality in migrants living with HIV in western Europe (1997-2013): a collaborative cohort study.

Migrants Working Group on behalf of COHERE in EuroCoord. Lancet HIV. 2015 Dec;2(12):e540-9. doi: 10.1016/S2352-3018(15)00203-9. Epub 2015 Nov 18.

Background: Many migrants face adverse socioeconomic conditions and barriers to health services that can impair timely HIV diagnosis and access to life-saving treatments. We aimed to assess the differences in overall mortality by geographical origin in HIV-positive men and women using data from COHERE, a large European collaboration of HIV cohorts from 1997 to 2013.

Methods: In this observational cohort study, we included HIV-positive, antiretroviral-naive people accessing care in western Europe from COHERE. Individuals were eligible if enrolled in a cohort that collected information on geographical origin or ethnic origin from Jan 1, 1997, to March 19, 2013, aged 18-75 years, they had available information about sex, they were not infected perinatally or after the receipt of clotting factor concentrates, and were naive to combination antiretroviral therapy at cohort entry. Migrants' origins were grouped into seven regions: western Europe and similar countries (Australia, Canada, New Zealand, and the USA); eastern Europe; North Africa and the Middle East; sub-Saharan Africa; Latin America; the Caribbean; and Asia and the rest of Oceania (excluding Australia and New Zealand). Crude and adjusted mortality rate ratios were calculated by use of Poisson regression stratified by sex, comparing each group with the native population. Multiple imputation with chained equations was used to account for missing values.

Findings: Between Oct 25, 1979, and March 19, 2013, we recruited 279 659 individuals to the COHERE collaboration in EuroCoord. Of these 123 344 men and 45 877 women met the inclusion criteria. Our data suggested effect modification by transmission route (pinteraction=0.12 for men; pinteraction=0.002 for women). No significant difference in mortality was identified by geographical origin in men who have sex with men. In heterosexual populations, most migrant men had mortality lower than or equal to that of native men, whereas no group of migrant women had mortality lower than that in native women. High mortality was identified in heterosexual men from Latin America (rate ratio [RR] 1.46, 95% CI 1.00-2.12, p=0.049) and heterosexual women from the Caribbean (1.48, 1.29-1.70, p<0.0001). Compared with that in the native population, mortality in injecting drug users was similar or low for all migrant groups.

Interpretation: Characteristics of and risks faced by migrant populations with HIV differ for men and women and for populations infected heterosexually, by sex between men, or by injecting drug use. Further research is needed to understand how inequalities are generated and maintained for the groups with higher mortality identified in this study.

Abstract access 

Editor’s notes: This topical analysis on migrant health from the large COHERE collaboration examined mortality in people living with HIV who are treatment-naïve and enrolling for care in 11 western European countries. Routinely collected data were analysed to explore differences in mortality by region of origin. Overall, few differences in mortality were seen between migrant and native populations, with a general trend of similar or lower mortality among migrants than native populations.  However, diversity within migrant groups even from the same region makes it challenging to interpret summary data. The authors provide interesting insights into these difficulties. For example, the reasons for migration are likely to result in different socio-economic conditions in the host country, but heterogeneity in mortality between sub-groups may be masked when looking at overall mortality in migrants compared with the native population. The authors discuss both the “healthy migrant effect” (the fact that it is often healthier, younger populations who are able to migrate), and the “salmon bias” (the fact people who are ill often return to their place of origin). Both of these effects can lead to an observed lower disease burden in migrants than native populations. At a time when immigration is a hotly debated issue in western Europe this study highlights the challenges in assessing migrant health and the need for further empirical and methodological research in this area.

Europe
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Effective pre-conception ART eliminates mother-to-child transmission

No perinatal hiv-1 transmission from women with effective antiretroviral therapy starting before conception.

Mandelbrot L, Tubiana R, Le Chenadec J, Dollfus C, Faye A, Pannier E, Matheron S, Khuong MA, Garrait V, Reliquet V, Devidas A, Berrebi A, Allisy C, Elleau C, Arvieux C, Rouzioux C, Warszawski J, Blanche S, Group A-ES. Clin Infect Dis. 2015 Dec 1;61(11):1715-25. doi: 10.1093/cid/civ578. Epub 2015 Jul 21.

Background: The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT.

Methods: A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation.

Results: The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9-8.2).

Conclusions: Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL.

Abstract access 

Editor’s notes: The risk of HIV transmission from mother-to-child is around 15-45% in the absence of maternal antiretroviral therapy (ART). This study illustrates that the risk of mother-to-child transmission is virtually eliminated when ART is started prior to conception and plasma viral load (VL) is undetectable at delivery. These findings provide further evidence supporting the implementation of Option B+ (lifelong ART as early as possible in all HIV-positive pregnant women regardless of CD4 count and VL) in low-income countries. In these settings, effectiveness of pre-conception ART will be dependent on retention in care so that women remain virologically suppressed for subsequent pregnancies. Robust surveillance data of pregnancy outcomes and other short-term and long-term risks of ART on the foetus, such as congenital malformations, and on the infant, such as pre-term birth, are also necessary to confirm that the benefit of pre-conception ART outweighs any harm.

Europe
France
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Viral load monitoring could be cost-effective

Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

Working Group on Modelling of Antiretroviral Therapy Monitoring Strategies in Sub-Saharan Africa, Phillips A, Shroufi A, Vojnov L, Cohn J, Roberts T, Ellman T, Bonner K, Rousseau C, Garnett G, Cambiano V, Nakagawa F, Ford D, Bansi-Matharu L, Miners A, Lundgren JD, Eaton JW, Parkes-Ratanshi R, Katz Z, Maman D, Ford N, Vitoria M, Doherty M, Dowdy D, Nichols B, Murtagh M, Wareham M, Palamountain KM, Chakanyuka Musanhu C, Stevens W, Katzenstein D, Ciaranello A, Barnabas R, Braithwaite RS, Bendavid E, Nathoo KJ, van de Vijver D, Wilson DP, Holmes C, Bershteyn A, Walker S, Raizes E, Jani I, Nelson LJ, Peeling R, Terris-Prestholt F, Murungu J, Mutasa-Apollo T, Hallett TB, Revill P. Nature. 2015 Dec 3;528(7580):S68-76. doi: 10.1038/nature16046.

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Abstract Full-text [free] access

 Editor’s notes: There has been much debate concerning how best to monitor antiretroviral therapy (ART) in resource-limited settings. In the early stages of ART roll-out, there were concerns that if ART monitoring required laboratory testing, the high cost would divert resources away from treatment delivery. Guidelines were drawn up to allow monitoring based on clinical features, alone or with CD4 count monitoring. However, clinical and CD4 monitoring proved to be neither sensitive nor specific when compared to viral load monitoring. In practice, the number of people switched to second-line ART in resource-limited settings has been lower than predicted, particularly where monitoring is clinical or CD4-based. This raises concerns that, in the absence of viral load monitoring, some people will acquire resistance to first-line ART, and this will remain undetected, with the person receiving ineffective treatment for a prolonged period, resulting in the accumulation of resistance mutations. This could threaten the effectiveness of future treatment options, and increases the risk of transmission of drug-resistant viruses. In addition, the poor specificity of clinical and CD4-based definitions of “treatment failure” means that if these definitions are used to make decisions about switching to second line ART, many people who, in reality, have virologic suppression may be inappropriately switched to second-line ART.

Increasingly, there are calls for viral load monitoring to be made more widely available. This is technically challenging, particularly in remote areas. Dried blood spot samples are an alternative method for specimen collection and transport which is practical for remote facilities. Viral load monitoring using dried blood spots has been implemented in some settings. Interpretation of results needs to take account of the lower sensitivity and specificity when compared to viral load assays based on plasma.

This study used a mathematical model to explore outcomes and cost-effectiveness of a range of ART monitoring strategies. The authors found that monitoring based on viral load measurements using dried blood spots was cost-effective. The model assumed that in scenarios with clinical and/or CD4 monitoring patient visits would be three-monthly, whereas in the viral load monitoring scenario, individuals with suppressed viral load would attend clinic for monitoring less frequently (hence the term “viral load-informed differentiated care”). The reduction in visit frequency for people with suppressed viral load was the main driver of cost saving in this scenario.

The cost-effectiveness estimates considered only health sector costs and ignored any patient costs.  Even when treatment and care are free of charge, people incur substantial costs to attend clinics for HIV care, particularly because of loss of income and transport costs. If patient costs had been included, the savings due to reduced visit frequency would almost certainly be even greater.

The accuracy of models is inevitably dependent on the underlying assumptions (described in detail and with admirable clarity in the paper’s accompanying on-line supplement). Cost-effectiveness was sensitive to the cost of viral load monitoring, assumed to be $22 per test based on dried blood spots. These results support efforts to increase access to viral load monitoring. As the authors comment, empirical data from programmes employing viral load-informed differentiated care as a monitoring strategy would be very useful. 

Africa
Zimbabwe
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