Articles tagged as "Europe"

Do people living with HIV live well with HIV in the era of antiretroviral therapy?

Editor’s notes: As treatment for HIV becomes increasingly widespread, and HIV-related deaths continue to decline, more and more attention is being paid to chronic non-communicable diseases and to the overall quality of life of people living with HIV.  However, despite 71% of people living with HIV in sub-Saharan Africa there is little research on the impact of illness and treatment on quality of life in the region.

Nyongesa and colleagues provide a fascinating mixed methods study, nested within a larger study of children and adolescents with HIV, which begins to formulate and validate a culturally appropriate tool to measure quality of life in the Swahili speaking population of coastal Kenya.  They used the functional assessment of HIV infection (FAHI) questionnaire as the starting point.  This is an HIV specific adaptation of a tool initially used among people with cancer and widely validated and studied in European and US based populations. 47 questions are used to assess HIV-specific quality of life in five domains: physical; emotional; functional and global well being; social; and cognitive functioning.

Following a scoping literature review, the authors used qualitative interviews with 38 participants living with HIV (largely female [27]) to explore their perceptions of the impact of HIV in the day-to-day life of people living with HIV in general. The issues raised overlapped with all the domains of FAHI except cognitive functioning, which the authors suggest is perhaps under-recognized when there are many competing stressors on people’s lives.  The participants then answered a draft version of the FAHI, which had been translated, back translated and reviewed in a group to ensure comprehension and relevance.  Following adaptation, the FAHI Swahili version was then administered to a sample of 103 randomly selected study participants living with HIV and on antiretroviral therapy from the same study site.  The sample was almost entirely female (94%) reflecting their availability at the parent study centre, which focussed on children and adolescents living with HIV.  Overall, the authors conclude that the new adaptation of the tool seems appropriate for further research studies on quality of life among people living with HIV on treatment in East Africa.  While the study provides a great example of a serious approach to develop, standardize and validate a culturally appropriate tool, the qualitative results also provide considerable insight into the many ways in which HIV affects these Kenyan’s lives beyond the purely medical.  Well worth reading the open access paper.

A study in Europe focussed specifically on the health-related domain of quality of life in Amsterdam.  Langebeek and colleagues used two tools that are well validated in European settings to assess physical and mental health related quality of life in 541 individuals living with HIV and 526 control participants without HIV.  HIV infection was clearly associated with worse quality of life, both mental and physical despite most participants being well controlled on ART.  As we might expect,  people who had multiple co-morbidities were less likely to have a good quality of life regardless of HIV status, but HIV remained an independent predictor of poor quality of life.  For mental health, HIV and younger age were both independently associated with less good quality of life.  The clear message is that we need to look beyond antiretroviral therapy and provide good holistic care including both mental and physical health services for people living with HIV, particularly as the population gets older.

A related study from Gonciulea and colleagues shows that among older men living with HIV, there is a significant increase in the risk of osteoporosis related fractures.  Bone demineralization is known to occur with risk factors such as age, sex, and low body mass index (BMI).However, increasingly studies are showing that HIV-related factors, such as antiretroviral medicines, ongoing viral replication and ongoing inflammation, are also potential risk factors. The authors used the multicenter AIDS cohort study to compare fracture incidence rates among 1221 men living with HIV and 1408 HIV-negative men.  Both cohorts were aged over 40 years.  As expected, fractures occurred more commonly as people got older, but the people living with HIV developed more fractures at an earlier age.  This study therefore reinforces the previous one, with the possibility to offer osteoporosis screening to men over the age of 50 who are living with HIV.

Petraglia and colleagues also explored the challenge of osteoporosis in people living with HIV.  Chronic obstructive pulmonary disease is known to be associated with low bone mineral density (BMD) and greater fracture risk in HIV negative smokers. In fact the finding of emphysema alone on CT imaging is a strong, independent predictor of osteoporosis in this group. We are beginning to observe obstructive lung disease as a common comorbidity in people living with HIV and emphysema has been shown to occur at an earlier age with less tobacco exposure in HIV positive smokers.  The authors therefore aimed to determine whether CT scans alone could predict who would turn out to have osteoporosis among people living with HIV.  As expected, they found that, among 164 people living with HIV, age; smoking and emphysema on CT scan were all associated with reduced BMD in the thoracic spine (estimated from the CT scan).  However, they also found that the emphysematous changes were an independent marker for this measure of osteoporosis regardless of age, sex, smoking, and use of antiretroviral medicines or steroids.  If a CT scan or lung function test suggests obstructive airways disease or emphysema, we should have a higher index of suspicion for osteoporosis among people living with HIV.

A mixed methods approach to adapting and evaluating the functional assessment of HIV infection (FAHI), Swahili version, for use with low literacy populations.

Nyongesa MK, Sigilai A, Hassan AS, Thoya J, Odhiambo R, Van de Vijver FJ, Newton CR, Abubakar A. PLoS One. 2017 Apr 5;12(4):e0175021. doi: 10.1371/journal.pone.0175021. eCollection 2017.

Background: Despite bearing the largest HIV-related burden, little is known of the Health-Related Quality of Life (HRQoL) among people living with HIV in sub-Saharan Africa. One of the factors contributing to this gap in knowledge is the lack of culturally adapted and validated measures of HRQoL that are relevant for this setting.

Aims: We set out to adapt the Functional Assessment of HIV Infection (FAHI) Questionnaire, an HIV-specific measure of HRQoL, and evaluate its internal consistency and validity.

Methods: The three phase mixed-methods study took place in a rural setting at the Kenyan Coast. Phase one involved a scoping review to describe the evidence base of the reliability and validity of FAHI as well as the geographical contexts in which it has been administered. Phase two involved in-depth interviews (n = 38) to explore the content validity, and initial piloting for face validation of the adapted FAHI. Phase three was quantitative (n = 103) and evaluated the internal consistency, convergent and construct validities of the adapted interviewer-administered questionnaire.

Results: In the first phase of the study, we identified 16 studies that have used the FAHI. Most (82%) were conducted in North America. Only seven (44%) of the reviewed studies reported on the psychometric properties of the FAHI. In the second phase, most of the participants (37 out of 38) reported satisfaction with word clarity and content coverage whereas 34 (89%) reported satisfaction with relevance of the items, confirming the face validity of the adapted questionnaire during initial piloting. Our participants indicated that HIV impacted on their physical, functional, emotional, and social wellbeing. Their responses overlapped with items in four of the five subscales of the FAHI Questionnaire establishing its content validity. In the third phase, the internal consistency of the scale was found to be satisfactory with subscale Cronbach's α ranging from 0.55 to 0.78. The construct and convergent validity of the tool were supported by acceptable factor loadings for most of the items on the respective sub-scales and confirmation of expected significant correlations of the FAHI subscale scores with scores of a measure of common mental disorders.

Conclusion: The adapted interviewer-administered Swahili version of FAHI questionnaire showed initial strong evidence of good psychometric properties with satisfactory internal consistency and acceptable validity (content, face, and convergent validity). It gives impetus for further validation work, especially construct validity, in similar settings before it can be used for research and clinical purposes in the entire East African region.

Abstract Full-text [free] access 

Impact of co-morbidity and aging on health-related quality of life in HIV-positive and HIV-negative individuals.

Langebeek N, Kooij KW, Wit FW, Stolte IG, Sprangers MAG, Reiss P, Nieuwkerk PT; AGEhIV Cohort Study Group. AIDS. 2017 Apr 19. doi: 10.1097/QAD.0000000000001511. [Epub ahead of print].

Background: HIV-infected individuals may be at risk for the premature onset of age-associated non-communicable co-morbidities. Being HIV-positive, having comorbidities and being of higher age may adversely impact health-related quality of life (HRQL). We investigated the possible contribution of HIV infection, co-morbidities, and age on HRQL and depression.

Methods: HIV-infected individuals and uninfected controls from the AGEhIV Cohort Study were screened for the presence of co-morbidities. They completed the Short Form 36-item Health Survey to assess HRQL and the nine-item Patient Health Questionnaire to assess depression. Linear and logistic regression were used to investigate to which extent co-morbidities, aging and HIV infection were independently associated with HRQL and depression.

Results: HIV-infected individuals (n = 541) reported significantly worse physical and mental HRQL and had a higher prevalence of depression than HIV-uninfected individuals (n = 526). A higher number of co-morbidities and HIV-positive status were each independently associated with worse physical HRQL, whereas HIV-positive status and younger age were independently associated with worse mental HRQL and more depression. The difference in physical HRQL between HIV-positive and HIV-negative individuals did not become greater with a higher number of co-morbidities or with higher age.

Conclusions: In a cohort of largely well-suppressed HIV-positive participants and HIV-negative controls, HIV-positive status was significantly and independently associated with worse physical and mental HRQL and with an increased likelihood of depression. Our finding that a higher number of co-morbidities was independently associated with worse physical HRQL reinforces the importance to optimize prevention and management of co-morbidities as the HIV-infected population continues to age.

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 An increased rate of fracture occurs a decade earlier in HIV+ compared to HIV- men in the Multicenter AIDS Cohort Study (MACS).

Gonciulea A, Wang R, Althoff KN, Palella FJ, Lake J, Kingsley LA, Brown TT. AIDS. 2017 Apr 3. doi: 10.1097/QAD.0000000000001493 [Epub ahead of print].

Objectives: To determine the incidence and age-related fracture risk among HIV-infected (HIV+) and uninfected men (HIV-). To evaluate factors independently associated with fracture risk.

Design: Prospective, multicenter cohort study of men with or at risk for HIV.

Methods: Outcome measures: 1) all fractures (excluding skull, face, digits) and 2) fragility fractures (vertebral column, femur, wrist, humerus) were collected semiannually in 1221 HIV+ and 1408 HIV- men ≥ age 40. Adjusted incident rate ratios (aIRR) with an interaction term for age (40-49, 50-59, ≥60 years) and HIV serostatus were estimated with Poisson regression models accounting for additional risk factors.

Results: Fracture incidence increased with age among both HIV+ and HIV- men. While there was no significant difference in fracture incidence by HIV serostatus among men aged 40-49 years, the HIV+ men aged 50-59 years had a significantly higher incidence of all fractures (aIRR = 2.06 [1.49, 2.84]) and fragility fractures (aIRR = 2.06 [1.21, 3.50]) compared with HIV- participants of similar age. HIV modified the effect of age on all fractures (p = 0.002) but did not significantly modify the effect for fragility fractures (p = 0.135). Hypertension increased the rate of all fractures by 32% after adjustment for covariates (aIRR = 1.32 [1.04, 1.69]).

Conclusions: Fracture incidence increased with age among HIV+ and HIV- men but was higher among HIV+ men. A significant increase in fracture incidence was found among 50-59-year-old HIV+ men, highlighting the importance of osteoporosis screening for HIV infected men above the age of 50.

Abstract access 

Emphysema is associated with thoracic vertebral bone attenuation on chest CT scan in HIV-infected individuals.

Petraglia A, Leader JK, Gingo M, Fitzpatrick M, Ries J, Kessinger C, Lucht L, Camp D, Morris A, Bon J. PLoS One. 2017 Apr 27;12(4):e0176719. doi: 10.1371/journal.pone.0176719. eCollection 2017.

Background: Age-related chronic diseases are prevalent in HIV-infected persons in the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and emphysema have separately been shown to occur at a younger age and with lesser risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV infected smokers, emphysema has been shown to independently predict low BMD. We hypothesized that emphysema would independently associate with thoracic vertebral bone attenuation, a surrogate for bone mineral density, in HIV-infected individuals.

Methods: Clinical, pulmonary function, and radiographic data were analyzed for 164 individuals from the University of Pittsburgh's HIV Lung Research Center cohort. Chest CT scans were used to quantify emphysema and compute Hounsfield Unit (HU) attenuation of the 4th, 7th, and 10th thoracic vertebrae. The association between mean HU attenuation values across the three vertebrae and radiographic emphysema, age, sex, body mass index (BMI), steroid use, viral load, CD4 count, and forced expiratory volume in the first second (FEV1) was assessed by univariate and multivariate analyses.

Results: In univariate analysis, mean HU attenuation decreased with increasing age (p<0.001), pack years (p = 0.047), and percent emphysema (p<0.001). In a multivariable model, including pack years, age, sex, ART and steroid use, greater emphysema was independently associated with this surrogate marker of BMD in HIV-infected individuals (p = 0.034).

Conclusions: The association of emphysema with thoracic bone attenuation in HIV-infected individuals is consistent with previous reports in non-HIV infected smokers. These findings suggest that emphysema should be considered a potential marker of osteoporosis risk in HIV-infected individuals.

Abstract Full-text [free] access 

Africa, Europe, 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.

Abstract access 

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.

Abstract access 

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.

Abstract access 

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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Short and sweet? Do study participants prefer shorter or longer consent forms? Do they understand the contents?

Editor’s notes: As described above in the HOLA en Grupos study, engagement and partnership is vital if HIV research is to produce useful and relevant results.  The ethics of research involving human subjects continues to evolve but the key principles laid out by Beauchamp and Childress in 1989 remain central.  The principles of autonomy, non-maleficence, beneficence, and justice, have been extremely influential in the field of medical ethics, and are fundamental for understanding the current approach to ethical assessment in health care.

Autonomy implies that research participants should be able to consent willingly to join a research study and a key part of that informed consent process is usually a written “consent form” that is signed by the participant.  However, a major challenge is often to ensure that on the one hand all relevant information about possible benefits and harms is included in the information and on the other hand that the consent process is manageable and appropriate for the participant.

In the largest study of its kind to date, Grady and colleagues embedded a randomized trial within the larger randomized START trial (comparing immediate with deferred start of antiretroviral medicines in people with early HIV infection).  Around 4000 participants in START were allocated according to their 154 research sites, which were randomly assigned to the original, lengthy and somewhat complicated consent form, or to a simplified, shorter consent form with much more attention paid to ease of comprehension and readability.  The shorter form was still around 1800 words long (compared to the almost 6000 of the original) and was only a little easier to read, because the sponsors of the study needed to be certain that all the information demanded by current guidelines was included.

Surprisingly, there was no overall difference in either the primary outcome (an understanding that participants’ treatment would be randomly allocated) or in overall comprehension of aspects of the study.  In other words, the authors did NOT find the advantages that they were expecting from the modified consent form.

However, various clear trends emerge from the data that are relevant to future research too.  Those with less education were clearly less able to understand the randomization approach.  73% of the 1240 participants who had not attended high school compared to more than 90% of the 935 who had completed a university degree or postgraduate education answered the primary question on randomization correctly. The START study team were diligent in explaining the study to potential participants before presenting the informed consent form, with around a half of participants reporting more than an hour of explanation prior to being asked for consent, and more than 80% of sites reporting that participants understood the study “very well” prior to the consent process.  There was also a clear trend for participants from sites that had been involved in previous HIV research to understand the process better (rising from 69% in those with no previous HIV studies to 85% in those with more than 10).

Increasingly HIV prevention researchers are aiming to work with populations that have high ongoing incidence of HIV.  In a world where treatment is increasingly widespread and overall numbers of infections have fallen somewhat, this means that researchers will tend to be working with more and more disadvantaged populations where many participants may be less well educated and less familiar with research.  This important study makes it clear that the ethical principle of autonomy requires an ongoing process that goes far beyond the choice of words in a consent form.  Research must build trust between researchers and participants.  The research team should explain carefully and in appropriate ways what is involved in the study and what options participants have. Study teams should build a governance process into the research so that participants can have confidence that any risks of the research, both for them as individuals, but also often for the community or group to which they belong, are monitored and mitigated.  In this way potentially vulnerable individuals may still be recruited into important research projects and contribute to the ways in which science can end the epidemic.

A randomized trial comparing concise and standard consent forms in the START trial.

Grady C, Touloumi G, Walker AS, Smolskis M, Sharma S, Babiker AG, Pantazis N, Tavel J, Florence E, Sanchez A, Hudson F, Papadopoulos A, Emanuel E, Clewett M, Munroe D, Denning E; INSIGHT START Informed Consent substudy Group PLoS One. 2017 Apr 26;12(4):e0172607. doi: 10.1371/journal.pone.0172607. eCollection 2017.

Background: Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed.

Methods: We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START). Interested sites were randomized to standard or concise consent forms for all individuals signing START consent. Participants completed a survey measuring comprehension of study information and satisfaction with the consent process. Site personnel reported usual site consent practices. The primary outcome was comprehension of the purpose of randomization (pre-specified 7.5% non-inferiority margin).

Results: 77 sites (2429 participants) were randomly allocated to use standard consent and 77 sites (2000 participants) concise consent, for an evaluable cohort of 4229. Site and participant characteristics were similar for the two groups. The concise consent was non-inferior to the standard consent on comprehension of randomization (80.2% versus 82%, site adjusted difference: 0.75% (95% CI -3.8%, +5.2%)); and the two groups did not differ significantly on total comprehension score, satisfaction, or voluntariness (p>0.1). Certain independent factors, such as education, influenced comprehension and satisfaction but not differences between consent groups.

Conclusions: An easier to read, more concise consent form neither hindered nor improved comprehension of study information nor satisfaction with the consent process among a large number of participants. This supports continued efforts to make consent forms more efficient.

Trial registration: Informed consent substudy was registered as part of START study in clinicaltrials.gov #NCT00867048, and EudraCT # 2008-006439-12.

Abstract Full-text [free] access 

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Where are we heading with the horrible interaction between human papillomavirus (HPV) and HIV?

Editor’s notes: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world.  There are over 200 different strains of HPV, distinguished by genetic typing.  The strains are classified into high-risk and low-risk based on their associations with the development of cervical cancer, but also genital warts and anal cancer.  HPV16 is the most common high-risk strain and is found in about half of cervical cancers and 70% of anal cancers.  Although anal cancer is much less common than cervical cancer among women, there is clear evidence that women living with HIV are at greater risk not only of cervical cancer but also of anal cancer.

In a study in Vitoria, Brazil, Volpini and colleagues collected cervical and anal samples from 126 women living with HIV who had recently had a normal Pap smear, and so did not already have pre-cancerous lesions in the cervix.  They found DNA from HPV in 71% of the women. 39% of women had HPV in cervical samples, while 60% had HPV in anal samples.

HPV16 was the most prevalent type at the cervical and anal sites (9% and 18%, respectively).  Other high risk strains were found in the cervical samples from more than 30% of women and in the anal samples of another 12% of women (some women had multiple strains). All currently available vaccines protect against HPV16 and one also protects against HPV45 and 31 (which accounted for almost half of the remaining high risk strains from the cervical samples).  The vaccine works best when given before any HPV infection, and is therefore recommended for girls before they become sexually active.  However, persistence and clearance of HPV is a dynamic process and the possible benefits of vaccination in those already infected are not yet clear.

Testing for HPV is becoming increasingly sophisticated, with molecular technology becoming available that allows detection of DNA and strain typing.  It seems very probable that women living with HIV with high-risk strains in either cervical or anal samples are at greater risk of developing cancer and therefore need additional more intense screening to detect and treat any pre-cancerous abnormalities in their epithelium prior to the development of invasive cancers.  Current guidelines already recommend that women living with HIV are offered Pap smears more regularly than their HIV-negative peers.  DNA based technology may make it possible to offer a more targeted approach to women at the most risk.

In the meantime, encouraging HPV vaccination among schoolgirls (and eventually boys too) is a long term prevention measure.  Ensuring that HPV screening services and HIV prevention and care services are well co-ordinated or even integrated is something that will have an immediate impact on preventing deaths from cervical cancer.  Incorporating molecular testing might help us to reduce the incidence of anal cancer too.

The high prevalence of HPV and HPV16 European variants in cervical and anal samples of HIV-seropositive women with normal Pap test results.

Volpini LPB, Boldrini NAT, de Freitas LB, Miranda AE, Spano LC. PLoS One. 2017 Apr 20;12(4):e0176422. doi: 10.1371/journal.pone.0176422. eCollection 2017.

Human immunodeficiency virus (HIV)-seropositive women are more likely to have anogenital cancer, and high risk-HPV (HR-HPV) infection is the main associated factor. Between August 2013 and December 2015, we conducted a descriptive study to determine the HPV genotypes and HPV16 variants in cervical and anal samples of HIV-seropositive women with a normal Pap test. The viral DNA was amplified by PCR using the PGMY09/11 set of primers. Reverse line blot (RLB), restriction fragment length polymorphism (RFLP) and sequencing assays were used to determine the HPV genotypes. HPV16 variants were identified by gene sequencing. We found a high frequency of HR-HPV (60.3%; 76/126) at the anogenital site among HIV-seropositive women and without association with anal intercourse. HPV16 and European variant predominated among the HR-HPV. Mixed infections with at least three different HPV types were common, particularly at the anal site. CD4+ T-cell counts below 500 cells/mm3, a HIV viral load above 50 copies/mL and an age of 18 to 35 years old were all related to HPV anal infection. Our study showed a high frequency of HR-HPV in both cervical and anal sites of women with negative cytology belonging to a risk group for the development of anogenital cancer.

Abstract Full-text [free] access 

Cancers, Comorbidity
Europe
Brazil
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Non-communicable diseases and co-morbidities – the flip side of successful ART programmes?

Editor’s notes: As the population of people living with HIV grows older and lives longer, the importance of non-communicable diseases is increasing.  Several studies this month explored various aspects of this intersection.

An encouraging study from Spain by Sorigué M et al., analysed the outcomes of patients with advanced stage Hodgkin’s lymphoma, a relatively common cancer both among people living with HIV and the HIV-negative population. The authors showed that, in the era of combined antiretroviral therapy, the complete response rate and ten year survival were not significantly different among people living with HIV (89% and 73%) and HIV negative people (91% and 68%).

Another broadly encouraging study from Ireland by Tinago W et al., followed up 384 people (176 living with HIV) to determine changes over three years in their bone mineral density (BMD).  BMD was somewhat lower in the people living with HIV, despite the group being younger on average.  As expected, BMD gradually fell with increasing age but the rate of bone loss was no different between people living with HIV and HIV negative people.  88% of the people living with HIV were on ART at the start of the study period.  Not having started ART among people living with HIV was associated with lower BMD and people who had started more recently showed the largest declines in BMD.  This suggests (as has previously been shown in cohorts of people living with HIV) that after an initial loss in BMD, the rate of loss stabilizes and is similar to HIV-negative people.  Interestingly, the authors did not show that overall exposure to tenofovir disproxil fumarate (TDF) was particularly associated with greater BMD loss over the course of follow up, despite several previous randomized trials confirming that TDF does cause BMD loss when it is started.

While on the subject of TDF, this month saw two important regulatory trials of tenofovir alafenamide (TAF), sponsored by the manufacturers Gilead Sciences.  630 people living with HIV on treatment with rilpivirine, emtricitabine and TDF whose viral load was supressed, were randomly allocated to remain on the same regimen or to swap the TDF for TAF.  TAF is a pro-drug, that reduces the plasma concentrations of tenofovir and is therefore expected to reduce the renal and bone toxicities associated with TDF while still delivering active drug to the cells where it is needed.  One year later, viral suppression was very similar in the two groups (94%).  There was also no significant difference seen in the side effects over this one year period, with no serious adverse events and 6% vs. 12% having some side effects in the TAF and TDF arms respectively [Orkin C and colleagues].

A related study by DeJesus E et al. with the same design was conducted among people taking efavirenz, emtricitabine and tenofovir, one of the most common first line regimens throughout the world. In this trial the efavirenz was switched to rilpivirine and the TDF to TAF.  875 people living with HIV whose viral load was supressed were randomized and after one year viral suppression was very similar in the two groups (90-92%).  There was also no significant difference seen in the side effects over this one year period, with no serious adverse events and 13% vs. 10% having some side effects in the rilpivirine -TAF and efavirenz-TDF arms respectively.

Returning to co-morbidities and non-communicable diseases, a study by Rodríguez-Arbolí E and colleagues in rural Tanzania has shown that 11.6% of people living with HIV who had not yet started ART had raised blood pressure.  A further 9.6% develop raised blood pressure during follow up, an incidence of 12 per 100 person years. The risk factors for developing hypertension were those well recognized in HIV-negative populations (age, renal disease and being overweight) and not specifically related to HIV infection, ART or immunological status.  The authors recommend integration of non-communicable disease screening and management into HIV care clinics but a larger conclusion might be to improve management of hypertension more generally, as it affects both people living with HIV and people without.

In contrast, a study by Pollack TM et al. from Viet Nam shows that smoking tobacco is associated with a higher viral load among people living with HIV presenting for ART.  As would be expected, other predictors of more advanced HIV disease such as lower CD4 counts and lower BMI and prior TB were all associated with a higher viral load at presentation.  Male sex was also significantly associated with a higher viral load.  The authors point out various other studies from Cameroon and the US that have shown similar and related interactions between smoking tobacco, viral load at presentation or viral load suppression or rebound on ART treatment.  Other studies in the US have not found this association.  One of the challenges is to separate behavioural factors that might be confounders – perhaps people who smoke are more likely to present late.  In this study there was not a clear dose response.  People who smoked more than ten cigarettes per day were actually somewhat less likely in this sample to have a higher viral load than people who smoked 1-10 cigarettes per day, but the numbers were too small to make statistically significant claims.  The authors suggest that oxidative stress and induction of the cytochrome P450 (CYP) pathway could explain the mechanism of smoking-related increased VL among HIV positive individuals.  While the study cannot prove cause and effect, there are already many reasons to promote tobacco cessation among people living with HIV and this may be an additional one.

The D:A:D study is a major prospective cohort that follows more than 49 000 people living with HIV in Europe, Australia and the USA.  Among the cohort, more than 4000 have developed chronic renal impairment.  A study by Ryom L et al. this month examined whether there was improvement, stabilisation or progression of renal impairment in the 2006 individuals who had additional measurements 2-3 years after renal impairment was first noted and explored risk factors for each.  On the one hand, they show that some ARVs (notably TDF and ritonavir-boosted atazanovir) are associated with worse renal outcomes, but on the other hand, they demonstrate that after stopping these nephrotoxic medicines, the kidneys recover or at least do not deteriorate further.  Once again, traditional risk factors (older age, high blood pressure and diabetes) are also important risk factors for the kidneys of people living with HIV.  As the population of people living with HIV gets older and lives longer, HIV care and traditional non-communicable disease management must overlap and coordinate.

HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine and dacarbazine.

Sorigué M, García O, Tapia G, Baptista MJ, Moreno M, Mate JL, Sancho JM, FeliuE, Ribera JM, Navarro JT. AIDS. 2017 Mar 29. doi: 10.1097/QAD.0000000000001487. [Epub ahead of print]

Objective: Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the study was to compare the characteristics, the response with treatment and survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients.

Design and methods: We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD.

Results: A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival 10-year disease-free survival 70% (41-99%) vs. 74% (57-91%), P = 0.907 and overall survival (OS) 10-year OS 73% (95% confidence interval52-94%) vs. 68% (51-85%), P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS.

Conclusion: Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.

Abstract access 

Predictors of longitudinal change in bone mineral density in a cohort of HIV-positive and negative patients.

Tinago W, Cotter AG, Sabin CA, Macken A, Kavanagh E, Brady JJ, McCarthy G,Compston J, Mallon PW; HIV UPBEAT Study Group.225. AIDS. 2017 Mar 13;31(5):643-652. doi: 10.1097/QAD.0000000000001372.

Objective: Although low bone mineral density (BMD) is prevalent in HIV, changes in BMD over time remain unclear. We aimed to compare rates of, and factors associated with, BMD change between HIV-positive and HIV-negative patients.

Methods: In a prospective, 3-year cohort, HIV-positive and HIV-negative patients provided annual demographic and clinical data, fasting bloods, and dual x-ray absorptiometry. Using longitudinal mixed models we compared and determined predictors of rate of change in BMD.

Results: Of 384 study participants (45.8% HIV positive), 120 contributed two and 264 contributed three BMD measurements. Those with HIV were younger [median interquartile range 39 (34-46) vs. 43 (35-50) years; P = 0.04], more often men (61 vs. 46%; P = 0.003), and less likely Caucasian (61 vs. 82%; P < 0.001).Although BMD was lower in those with HIV, BMD declined in both groups, with nonsignificant between-group difference in rate of BMD change over time. Within the HIV group, starting antiretroviral therapy (ART) within 3 months of enrolment was associated with greater BMD decline at all anatomical sites (all P < 0.001). Age more than 30 years, Caucasian ethnicity, and not being on ART during follow-up were associated with greater decline and higher parathyroid hormone associated with a smaller decline in BMD at the femoral neck. We found no association between BMD change and exposure to tenofovir disoproxil fumarate or protease inhibitors.

Conclusion: We observed no difference in rate of BMD decline regardless of HIV status and in HIV-positive patient, having started ART within the previous 3 months was the only factor associated with greater BMD decline at all three sites.

Abstract access 

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study.

Orkin C,  DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Vandercam B, de Wet J, Rockstroh J, Lazzarin A, Rijnders B, Podzamczer D, Thalme A, Stoeckle M, Porter D, Liu HC, Cheng A, Quirk E, SenGupta D, Cao H. Lancet HIV. 2017 Mar 1. pii: S2352-3018(17)30031-0. doi:10.1016/S2352-3018(17)30031-0. [Epub ahead of print]

Background: Tenofovir alafenamide, a tenofovir prodrug, results in 90% lower tenofovir plasma concentrations than does tenofovir disproxil fumarate, thereby minimising bone and renal risks. We investigated the efficacy, safety, and tolerability of switching to a single-tablet regimen containing rilpivirine, emtricitabine, and tenofovir alafenamide compared with remaining on rilpivirine, emtricitabine, and tenofovir disoproxil fumarate.

Methods: In this randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-1-infected adults were screened and enrolled at 119 hospitals in 11 countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA <50 copies per ml) on rilpivirine, emtricitabine, and tenofovir disoproxil fumarate for at least 6 months before enrolment and had creatinine clearance of at least 50 ml/min. Participants were randomly assigned(1:1) to receive a single-tablet regimen of either rilpivirine (25 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) or to remain on a single-tablet regimen of rilpivirine (25 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), with matching placebo, once daily for 96 weeks. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug and were on the tenofovir disoproxil fumarate regimen before screening were included in primary efficacy analyses. The primary endpoint was the proportion of participants with less than 50 copies per ml of plasma HIV-1 RNA at week 48 (by the US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 8%. This study was registered with clinicaltrials.gov, number NCT01815736.

Findings: Between Jan 26, 2015, and Aug 25, 2015, 630 participants were randomised (316 to the tenofovir alafenamide group and 314 to the tenofovir disoproxil fumarate group). At week 48, 296 (94%) of 316 participants on tenofovir alafenamide and 294 (94%) of 313 on tenofovir disoproxil fumarate had maintained less than 50 copies per ml HIV-1 RNA (difference -0·3%, 95·001% CI-4·2 to 3·7), showing non-inferiority of tenofovir alafenamide to tenofovir disoproxil fumarate. Numbers of adverse events were similar between groups. 20(6%) of 316 participants had study-drug related adverse events in the tenofovir alafenamide group compared with 37 (12%) of 314 in the tenofovir disoproxil fumarate group; none of these were serious.

Interpretation: Switching to rilpivirine, emtricitabine, and tenofovir alafenamide was non-inferior to continuing rilpivirine, emtricitabine, tenofovir disoproxil fumarate in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection.

Abstract access 

Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study.

DeJesus E, Ramgopal M, Crofoot G, Ruane P, LaMarca A, Mills A, Martorell CT, de Wet J, Stellbrink HJ, Molina JM, Post FA, Valero IP, Porter D, Liu Y, Cheng A, Quirk E, SenGupta D, Cao H. Lancet HIV. 2017 Mar 1. pii: S2352-3018(17)30032-2. doi:10.1016/S2352-3018(17)30032-2. [Epub ahead of print]

Background: Tenofovir alafenamide is a prodrug that reduces tenofovir plasma concentrations by 90% compared with tenofovir disoproxil fumarate, thereby decreasing bone and renal risks. The coformulation of rilpivirine, emtricitabine,and tenofovir alafenamide has recently been approved, and we aimed to investigate the efficacy, safety, and tolerability of switching to this regimen compared with remaining on coformulated efavirenz, emtricitabine, and tenofovir disoproxil fumarate.

Methods: In this randomised, double-blind, placebo-controlled, non-inferiority trial, HIV-1-infected adults were enrolled at 120 hospitals and outpatient clinics in eight countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA <50 copies per mL) on efavirenz, emtricitabine, and tenofovir disoproxil fumarate for at least 6 months before enrolment and had creatinine clearance of at least 50 mL/min. Participants were randomly assigned(1:1) to receive a single-tablet regimen of rilpivirine (25 mg), emtricitabine(200 mg), and tenofovir alafenamide (25 mg) or to continue a single-tablet regimen of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), with matching placebo. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50copies per mL at week 48 (assessed by the US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 8%. This study was registered with ClinicalTrials.gov, number NCT02345226.

Findings: Between Jan 26, 2015, and Aug 27, 2015, 875 participants were randomly assigned and treated (438 with rilpivirine, emtricitabine, and tenofovir alafenamide and 437 with efavirenz, emtricitabine, tenofovir disoproxil fumarate). Viral suppression at week 48 was maintained in 394 (90%) of 438 participants assigned to the tenofovir alafenamide regimen and 402 (92%) of 437 assigned to the tenofovir disoproxil fumarate regimen (difference -2·0%, 95·001% CI -5·9 to 1·8), demonstrating non-inferiority. 56 (13%) of 438 in participants in the rilpivirine, emtricitabine, and tenofovir alafenamide group experienced treatment-related adverse events compared with 45 (10%) of 437 in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group.

Interpretation: Switching to rilpivirine, emtricitabine, and tenofovir alafenamide from efavirenz, emtricitabine, and tenofovir disoproxil fumarate was non-inferior in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection.

Abstract access 

Incidence and risk factors for hypertension among HIV patients in rural Tanzania - A prospective cohort study.

Rodríguez-Arbolí E, Mwamelo K, Kalinjuma AV, Furrer H, Hatz C, Tanner M, Battegay M, Letang E; KIULARCO Study Group. PLoS One. 2017 Mar 8;12(3):e0172089. doi: 10.1371/journal.pone.0172089.eCollection 2017.

Introduction: Scarce data are available on the epidemiology of hypertension among HIV patients in rural sub-Saharan Africa. We explored the prevalence, incidence and risk factors for incident hypertension among patients who were enrolled in a rural HIV cohort in Tanzania.

Methods: Prospective longitudinal study including HIV patients enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2013 and 2015. Non-ART naïve subjects at baseline and pregnant women during follow-up were excluded from the analysis. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg on two consecutive visits. Cox proportional hazards models were used to assess the association of baseline characteristics and incident hypertension.

Results: Among 955 ART-naïve, eligible subjects, 111 (11.6%) were hypertensive at recruitment. Ten women were excluded due to pregnancy. The remaining 834 individuals contributed 7967 person-months to follow-up (median 231 days, IQR 119-421) and 80 (9.6%) of them developed hypertension during a median follow-up of 144 days from time of enrolment into the cohort [incidence rate 120.0 cases/1000 person-years, 95% confidence interval (CI) 97.2-150.0]. ART was started in 630 (75.5%) patients, with a median follow-up on ART of 7 months (IQR 4-14). Cox regression models identified age [adjusted hazard ratio (aHR) 1.34 per 10 years increase, 95% CI 1.07-1.68, p = 0.010], body mass index (aHR per 5 kg/m2 1.45, 95% CI 1.07-1.99, p = 0.018) and estimated glomerular filtration rate (aHR < 60 versus ≥ 60 ml/min/1.73 m2 3.79, 95% CI 1.60-8.99, p = 0.003) as independent risk factors for hypertension development.

Conclusions: The prevalence and incidence of hypertension were high in our cohort. Traditional cardiovascular risk factors predicted incident hypertension, but no association was observed with immunological or ART status. These data support the implementation of routine hypertension screening and integrated management into HIV programmes in rural sub-Saharan Africa.

Abstract  Full-text [free] access

Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam.

Pollack TM, Duong HT, Pham TT, Do CD, Colby D. PLoS One. 2017 Mar 7;12(3):e0173534. doi: 10.1371/journal.pone.0173534.eCollection 2017.

High HIV viral load (VL >100 000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100 000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1-10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15-3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75-2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100 000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use among HIV-infected patients.

Abstract  Full-text [free] access 

Predictors of eGFR progression, stabilisation or improvement after chronic renal impairment in HIV-positive individuals.

Ryom L, Mocroft A, Kirk O, Reiss P, Ross M, Smith C, Moranne O, Morlat P, Fux CA, Sabin C, Phillips A, Law M, Lundgren JD; D:A:D study group. AIDS. 2017 Mar 28. doi: 10.1097/QAD.0000000000001464. [Epub ahead of print]

Objectives: The objectives of this analysis were to investigate predictors of progression, stabilisation or improvement in eGFR after development of chronic renal impairment (CRI) in HIV-positive individuals.

Design: Prospective observational study.

Methods: D:A:D study participants progressing to CRI defined as confirmed, ≥ 3 months apart, eGFR ≤70  mL/min/1.73m were included in the analysis. The median of all eGFRs measured 24-36 months post-CRI was compared to the median eGFR defining CRI, and changes were grouped into: improvement (>+10 mL/min/1.73m), stabilisation (-10 to +10 mL/min/1.73m) and progression (<-10 mL/min/1.73m). Adjusted polynomial regression models assessed odds of better eGFR outcomes after CRI, assuming eGFR improvement is better than stabilisation which in turn is better than progression.

Results: Of 2006 individuals developing CRI, 21% subsequently improved eGFR, 67% stabilised and 12% progressed. Individuals remaining on TDF or boosted atazanavir (ATV/r) 24 months post-CRI had worse eGFR outcomes compared to those unexposed (TDF: 0.47 [0.35-0.63], ATV/r: 0.63 [0.48-0.82]). Individuals off TDF for 12-24 months (0.75 [0.50-1.13]) or off ATV/r for >12 months (1.17 [0.87-1.57]) had similar eGFR outcomes as those unexposed to these ARVs. Older age, hypertension, later date of CRI and diabetes were associated with worse eGFR outcomes.

Conclusion: Current TDF and ATV/r use after a diagnosis of CRI was associated with worse eGFR outcomes. In contrast, TDF and ATV/r discontinuation lead to similar longer-term eGFR outcomes as in those unexposed suggesting these drug-associated eGFR declines may be halted or reversed after their cessation.

Abstract access  

Comorbidity, HIV Treatment
Africa, Asia, Europe, Northern America, Oceania
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HIV-2 – not a global pandemic, but still causing challenges for diagnosis and treatment

Editor’s notes: HIV-2 is discussed much less than HIV-1 because it has not caused a global pandemic.  Nonetheless there are around 1-2 million people thought to be living with HIV-2, predominantly in West Africa and in Portugal and her historical connections (Brazil, Angola, Mozambique and India).  A useful review by de Mendoza C and colleagues from Spain highlights key features in the epidemiology, management and future directions for HIV-2.  The diagnosis is easy to miss and should be considered whenever routine HIV-1 tests give curious serological profiles.  There are also important differences when treating people living with HIV-2. HIV-2 cannot be treated with non-nucleoside reverse transcriptase inhibitors and some protease inhibitors do not work either. Viral load monitoring has not been commercialized, and so is often unreliable.  CD4 cell counts tend to drop more rapidly in HIV-1 and this has sometimes led to the suggestion that HIV-2 is a benign infection.  However, progression to an AIDS-like syndrome does occur, particularly in people who acquired HIV at a younger age.  The CD4 cell count recovery on antiretroviral therapy seem to be less effective in HIV-2 compared to HIV-1 infections. Failure and selection of drug resistance may be more frequent in HIV-2.

HIV-2 Epidemic in Spain - challenges and missing opportunities.

de Mendoza C, Cabezas T, Caballero E, Requena S, Amengual MJ, Peñaranda M, Sáez A, Tellez R, Lozano AB, Treviño A, Ramos JM, Pérez JL, Barreiro P, Soriano V; Spanish HIV-2 Network. AIDS. 2017 Mar 29. doi: 10.1097/QAD.0000000000001485. [Epub ahead of print]

HIV type 2 (HIV-2) is a neglected virus despite estimates of 1-2 million people infected worldwide. HIV-2 is less efficiently transmitted than HIV-1 by sex and from mother-to-child. Although AIDS may develop in HIV-2 carriers, it takes longer than in HIV-1-infected patients. In contrast with HIV-1 infection, there is no global pandemic caused by HIV-2, remaining the virus largely confined to West Africa. In a less extent and due to socioeconomic ties and wars, HIV-2 is prevalent in Portugal and its former colonies in Brazil, India, Mozambique and Angola. Globally, HIV-2 infections are steadily declining over time. A total of 338 cases of HIV-2 infection had been reported at the Spanish HIV-2 registry until December 2016, of whom 63% were male. Overall 72% were sub-Saharan Africans whereas 16% were native Spaniards. Dual HIV-1 and HIV-2 coinfection was found in 9% of patients. Heterosexual contact was the most likely route of HIV-2 acquisition in more than 90% of cases. Roughly one third presented with CD4 counts <200 cells/μL and/or AIDS clinical events. Plasma HIV-2 RNA was undetectable at baseline in 40% of patients. To date, one third of HIV-2 carriers have received antiretroviral therapy, using integrase inhibitors 32 individuals. New diagnoses of HIV-2 in Spain have remained stable since 2010 with an average of 15 cases yearly. Illegal immigration from Northwestern African borders accounts for over 75% of new HIV-2 diagnoses. Given the relatively large community of West Africans already living in Spain and the continuous flux of immigration from endemic regions, HIV-2 infection either alone or as coinfection with HIV-1 should be excluded once in all HIV-seroreactive persons, especially when showing atypical HIV serological profiles, immunovirological disconnect (CD4 count loss despite undetectable HIV-1 viremia) and/or high epidemiological risks (birth in or sex partners from endemic regions).

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Basic science, HIV
Europe
Spain
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Post-exposure prophylaxis – does it matter which medicines we use?

Editor’s notes: Two studies this month looked at alternative post-exposure prophylaxis (PEP) regimens.  PEP is often not well tolerated and this leads to non-completion of the one month course.  In London a randomized trial by Milinkovic A and colleagues compared the tolerability and completion rates between 213 individuals given twice daily maraviroc or ritonavir-boosted lopinavir in addition to daily tenofovir disproxil fumarate with emitricitabine (TDF-FTC) daily.  Completion rates were very similar (71% vs. 65%) but maraviroc was associated with fewer mild-moderate side effects (70% vs. 91%) and less use of anti-diarrhoeal medication (25% vs. 67%).  There were no serious side effects in either arm and similar numbers of individuals stopped taking their medication (18%). In Australia, in an open label, non-randomized study, 100 individuals were offered once daily dolutegravir as the third drug (also with TDF-FTC). 90 people completed the one month course, 9 were lost to follow up and one stopped because of headaches.  Side effects were also common in this study (similar to the London study); around a quarter of people complained of fatigue, nausea or diarrhoea [Mcallister J et al.]. Although no seroconversions were seen in either study, despite well documented risks at entry to treatment, the studies are not large enough to shed much light on the effectiveness of the regimens.  They demonstrate the ongoing challenges in finding PEP regimens that have fewer side effects.  Whether completion rates would be as high in less controlled settings than a clinical trial is not clear.  Nonetheless it seems that dolutegravir daily or maraviroc twice daily may be a suitable replacement for ritonavir-boosted lopinavir as the third drug for use as PEP.

 

Randomized controlled trial of the tolerability and completion of maraviroc compared with Kaletra® in combination with Truvada® for HIV post-exposure prophylaxis (MiPEP Trial).

Milinkovic A, Benn P, Arenas-Pinto A, Brima N, Copas A, ClarkeA, Fisher M, Schembri G, Hawkins D, Williams A, Gilson R; MiPEP Trial Team.J Antimicrob Chemother. 2017 Mar 20. doi: 10.1093/jac/dkx062. [Epub ahead ofprint]

Objectives: Post-exposure prophylaxis (PEP) for HIV is often poorly tolerated and not completed. Alternative PEP regimens may improve adherence and completion, aiding HIV prevention. We conducted a randomized controlled trial of a maraviroc-based PEP regimen compared with a standard-of-care regimen using ritonavir-boosted lopinavir.

Methods: Patients meeting criteria for PEP were randomized to tenofovir disoproxil/emtricitabine (200/245 mg) once daily plus ritonavir-boosted lopinavir (Kaletra ® 400/100 mg) or maraviroc 300 mg twice daily. The composite primary endpoint was completion of 28 days of the allocated PEP regimen without grade 3or 4 clinical or laboratory adverse events (AEs) related to the PEP medication.

Results: Two hundred and thirteen individuals were randomized (107 to maraviroc; 106 to Kaletra ® arm). Follow-up rates were high in both groups. There was no difference in the primary endpoint; 70 (71%) in the maraviroc and 64 (65%) in the Kaletra ® arm ( P  =   0.36) completed PEP without grade 3 or 4 AEs. Discontinuation of PEP was the same (18%) in both groups. There were no grade 3or 4 clinical AEs in either arm, but more grade 1 or 2 clinical AEs in the Kaletra ® arm (91% versus 70%; P < 0.001). Antidiarrhoeal medication use was higher in the Kaletra ® arm (67% versus 25%; P < 0.001). There were no HIV seroconversions in the study period.

Conclusions: The completion rate in the absence of grade 3 or 4 AEs was similar with both regimens. Maraviroc-based PEP was better tolerated, supporting its use as an option for non-occupational PEP.

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Dolutegravir with tenofovir disoproxil fumarate - emtricitabine as HIV post-exposure prophylaxis in gay and bisexual men.

Mcallister J, Towns JM, Mcnulty A, Pierce AB, Foster R, Richardson R, Carr A. AIDS. 2017 Mar 15. doi: 10.1097/QAD.0000000000001447. [Epub ahead of print]

Objectives: Completion rates for HIV post-exposure prophylaxis (PEP) are often low. We investigated the adherence and safety of dolutegravir (DTG 50 mg daily) with tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF-FTC) as3-drug PEP in gay and bisexual men (GBM).

Design: Open-label, single-arm study at 3 sexual health clinics and 2 emergency departments in Australia.

Methods: One hundred HIV-uninfected GBM requiring PEP received DTG plus TDF-FTC for 28 days. The primary endpoint was PEP failure (premature PEP cessation or primary HIV infection through Week 12). Additional endpoints were: adherence by self-report (n = 98) and pill count (n = 55); safety; and plasma drug levels at Day 28.

Results: PEP completion was 90% (95%CI 84% to 96%). Failures (occurring at a median 9 days, IQR 3-16) comprised loss to follow-up (9%) and adverse event resulting in study drug discontinuation (headache, 1%). No participant was found to acquire HIV through Week 12. Adherence to PEP was 98% by self-report and in the 55 participants with corresponding pill count data. The most common clinical adverse events (AEs) were fatigue (26%), nausea (25%), diarrhoea (21%), and headache (10%). There were only four Grade 3-4 subjective AEs. The most common laboratory AE was raised alanine aminotransferase (22%), but there was no case of clinical hepatitis. At Day 28, the mean estimated glomerular filtration rate (eGFR) decrease was 14 ml/min/1.73m (SD 17, p = 0.001); an eGFR of<60 ml/min/1.73m occurred in 3%.

Conclusions: DTG with TDF-FTC is a safe and well-tolerated option for once-daily PEP.

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Europe, Oceania
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Stigma and sex work

Editor’s notes: Two interesting studies this month looked at aspects of stigma.  There are big methodological challenges to the study of stigma.  Stigma comprises several different domains and few studies use standardized approaches to measurement that can be translated easily into other contexts.  A systematic review and meta-analysis concludes that people who feel more stigmatized are twice as likely to delay presenting for HIV care.  Gesesew HA and colleagues found only ten studies that met their pre-specified inclusion criteria, and five of these came from Ethiopia.  They acknowledge many of the challenges in combining the results of these ten studies into a single conclusion.  They recommend engagement of health care workers to try to reduce perceived stigma among people living with HIV.

The Nyblade L et al. study from Kenya emphasizes the perception of stigma among sex workers.  In a large sample of 497 females and 232 males, most reported experiencing stigma both verbal and measured from health care workers. For female sex workers, the anticipation of such stigma led to avoidance of health services for both HIV and non-HIV related conditions. In order to provide effective services for key populations, health care workers must be trained to be non-judgemental.  HIV services need to be provided in the context of an overall package of health care.

A study from Europe used ecological data to explore structural risks for HIV among sex workers.  Reeves A and colleagues used regression modelling with data on sex work policies from 27 countries.  They showed a strong correlation between criminalisation of sex work and higher prevalence of HIV among sex workers.  Although they included other factors such as the level of economic development and using drugs, the relatively small number of data points does mean that there may be other confounding factors that could not be measured or adjusted for.

Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis.

Gesesew HA, Tesfay Gebremedhin A, Demissie TD, Kerie MW, Sudhakar M, Mwanri L. PLoS One. 2017 Mar 30;12(3):e0173928. doi: 10.1371/journal.pone.0173928.eCollection 2017.

Background: Late presentation for human immunodeficiency virus (HIV) care is a major impediment for the success of antiretroviral therapy (ART) outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome) is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care.

Methods: Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: 'late HIV testing', 'late HIV diagnosis' and 'late presentation for HIV care after testing'. Data were extracted using a standardized Joanna Briggs Institute (JBI) data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value.

Results: Ten studies from low- and middle- income countries met the search criteria, including six (6) and four (4) case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3788 participants. Half (5) of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6-3.6, I2 = 79%).

Conclusions: High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should play a key role in informing and counselling patients on the benefits of early HIV testing or early entry to HIV care. Additionally, linking the systems and positive case tracing after HIV testing should be strengthened.

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The relationship between health worker stigma and uptake of HIV counseling and testing and utilization of non-HIV health services: the experience of male and female sex workers in Kenya.

Nyblade L, Reddy A, Mbote D, Kraemer J, Stockton M, Kemunto C, Krotki K, Morla J, Njuguna S, Dutta A, Barker C. AIDS Care. 2017 Mar 22:1-9. doi: 10.1080/09540121.2017.1307922. [Epub ahead of print]

The barrier HIV-stigma presents to the HIV treatment cascade is increasingly documented; however less is known about female and male sex worker engagement in and the influence of sex-work stigma on the HIV care continuum. While stigma occurs in all spheres of life, stigma within health services may be particularly detrimental to health seeking behaviors. Therefore, we present levels of sex-work stigma from healthcare workers (HCW) among male and female sex workers in Kenya, and explore the relationship between sex-work stigma and HIV counseling and testing. We also examine the relationship between sex-work stigma and utilization of non-HIV health services. A snowball sample of 497 female sex workers (FSW) and 232 male sex workers (MSW) across four sites was recruited through a modified respondent-driven sampling process. About 50% of both male and female sex workers reported anticipating verbal stigma from HCW while 72% of FSW and 54% of MSW reported experiencing at least one of seven measured forms of stigma from HCW. In general, stigma led to higher odds of reporting delay or avoidance of counseling and testing, as well as non-HIV specific services. Statistical significance of relationships varied across type of health service, type of stigma and gender. For example, anticipated stigma was not a significant predictor of delay or avoidance of health services for MSW; however, FSW who anticipated HCW stigma had significantly higher odds of avoiding (OR = 2.11) non-HIV services, compared to FSW who did not. This paper adds to the growing evidence of stigma as a roadblock in the HIV treatment cascade, as well as its undermining of the human right to health. While more attention is being paid to addressing HIV-stigma, it is equally important to address the key population stigma that often intersects with HIV-stigma.

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National sex work policy and HIV prevalence among sex workers: an ecological regression analysis of 27 European countries.

Reeves A, Steele S, Stuckler D, McKee M, Amato-Gauci A, Semenza JC. Lancet HIV. 2017 Mar;4(3):e134-e140. doi: 10.1016/S2352-3018(16)30217-X. Epub2017 Jan 25.

Background: Sex workers are disproportionately affected by HIV compared with the general population. Most studies of HIV risk among sex workers have focused on individual-level risk factors, with few studies assessing potential structural determinants of HIV risk. In this Article, we examine whether criminal laws around sex work are associated with HIV prevalence among female sex workers.

Method: We estimate cross-sectional, ecological regression models with data from 27 European countries on HIV prevalence among sex workers from the European Centre for Disease Control; sex-work legislation from the US State Department's Country Reports on Human Rights Practices and country-specific legal documents; the rule of law and gross-domestic product per capita, adjusted for purchasing power, from the World Bank; and the prevalence of injecting drug use among sex workers. Although data from two countries include male sex workers, the numbers are so small that the findings here essentially pertain to prevalence in female sex workers.

Findings: Countries that have legalised some aspects of sex work (n=17) have significantly lower HIV prevalence among sex workers than countries that criminalise all aspects of sex work (n=10; β=-2·09, 95% CI -0·80 to -3·37;p=0·003), even after controlling for the level of economic development (β=-1·86; p=0·038) and the proportion of sex workers who are injecting drug users (-1·93;p=0·026). We found that the relation between sex work policy and HIV among sex workers might be partly moderated by the effectiveness and fairness of enforcement, suggesting legalisation of some aspects of sex work could reduce HIV among sex workers to the greatest extent in countries where enforcement is fair and effective.

Interpretation: Our findings suggest that the legalisation of some aspects of sex work might help reduce HIV prevalence in this high-risk group, particularly in countries where the judiciary is effective and fair.

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Peer led activities increase HIV testing uptake among MSM

Effectiveness of peer-led interventions to increase HIV testing among men who have sex with men: a systematic review and meta-analysis.

Shangani S, Escudero D, Kirwa K, Harrison A, Marshall B, Operario D. AIDS Care. 2017 Feb 2:1-11. doi: 10.1080/09540121.2017.1282105. [Epub ahead of print]

HIV testing constitutes a key step along the continuum of HIV care. Men who have sex with men (MSM) have low HIV testing rates and delayed diagnosis, especially in low-resource settings. Peer-led interventions offer a strategy to increase testing rates in this population. This systematic review and meta-analysis summarizes evidence on the effectiveness of peer-led interventions to increase the uptake of HIV testing among MSM. Using a systematic review protocol that was developed a priori, we searched PubMed, PsycINFO and CINAHL for articles reporting original results of randomized or non-randomized controlled trials (RCTs), quasi-experimental interventions, and pre- and post-intervention studies. Studies were eligible if they targeted MSM and utilized peers to increase HIV testing. We included studies published in or after 1996 to focus on HIV testing during the era of combination antiretroviral therapy. Seven studies encompassing a total of 6205 participants met eligibility criteria, including two quasi-experimental studies, four non-randomized pre- and-post intervention studies, and one cluster randomized trial. Four studies were from high-income countries, two were from Asia and only one from sub-Saharan Africa. We assigned four studies a "moderate" methodological rigor rating and three a "strong" rating. Meta-analysis of the seven studies found HIV testing rates were statistically significantly higher in the peer-led intervention groups versus control groups (pooled OR 2.00, 95% CI 1.74-2.31). Among randomized trials, HIV testing rates were significantly higher in the peer-led intervention versus control groups (pooled OR: 2.48, 95% CI 1.99-3.08). Among the non-randomized pre- and post-intervention studies, the overall pooled OR for intervention versus control groups was 1.71 (95% CI 1.42-2.06), with substantial heterogeneity among studies (I2 = 70%, p < 0.02). Overall, peer-led interventions increased HIV testing among MSM but more data from high-quality studies are needed to evaluate effects of peer-led interventions on HIV testing among MSM in low- and middle-income countries.

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Editor’s notes: A key driver of the HIV epidemic is low uptake of HIV testing in many settings. This leads to a high proportion of individuals living with HIV being unaware of their status, failing to engage with care and treatment and hence being at risk of transmitting HIV to others. Recent reviews have illustrated that programmes led by members of the same peer group can be effective in promoting HIV-associated behavioural change and improving clinical outcomes. Gay men and other men who have sex with men can experience specific challenges associated with engagement with HIV care. This problem is particularly acute in resource poor regions due to very high levels of stigma.

This systematic review is the first to look specifically at the effectiveness of peer-led activities among gay men and other men who have sex with men. Seven studies were found which fulfilled the inclusion criteria of assessing the impact of peer-led activities on HIV testing uptake among gay men and other men who have sex with men. Four of these were in high income settings, and the others in Peru, Taiwan and Kenya. Each study illustrated a positive effect of peer-led activities on increasing HIV testing rates, and meta-analyses illustrated consistent effects when data were stratified by sub-groups (study methodology, study quality or setting). However, the generalizability of these studies to the entire population of gay men and other men who have sex with men is a concern recognized by the authors as the majority used gay-centric community venues to recruit participants. This is likely to exclude individuals who do not self-identify as being part of this community. Two studies, one in Taiwan and the other in Peru, used social-media as a mechanism of recruitment. This approach may lead to a wider recruitment, although not accessible to people without access to the internet.

Overall, this review emphasizes the potential of peer-led activities to overcome barriers to engage with testing and treatment experienced by gay men and other men who have sex with men and other hard to reach and high-risk sub-populations. It also illustrated the very limited current evidence available to assess such programmes.

 

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People who inject drugs living with HIV in Russia face more mental health issues and diminished quality of life

Psychiatric symptoms, quality of life, and HIV status among people using opioids in Saint Petersburg, Russia.

Desrosiers A, Blokhina E, Krupitsky E, Zvartau E, Schottenfeld R, Chawarski M. Drug Alcohol Depend. 2017 Mar 1;172:60-65. doi: 10.1016/j.drugalcdep.2016.12.007. Epub 2017 Jan 23.

Background: The Russian Federation is experiencing a very high rate of HIV infection among people who inject drugs (PWID). However, few studies have explored characteristics of people with co-occurring opioid use disorders and HIV, including psychiatric symptom presentations and how these symptoms might relate to quality of life. The current study therefore explored a.) differences in baseline psychiatric symptoms among HIV+ and HIV- individuals with opioid use disorder seeking naltrexone treatment at two treatment centers in Saint Petersburg, Russia and b.) associations between psychiatric symptom constellations and quality of life.

Methods: Participants were 328 adults enrolling in a randomized clinical trial evaluating outpatient treatments combining naltrexone with different drug counseling models. Psychiatric symptoms and quality of life were assessed using the Brief Symptom Inventory and The World Health Organization Quality of Life-BREF, respectively.

Results: Approximately 60% of participants were HIV+. Those who were HIV+ scored significantly higher on BSI anxiety, depression, psychoticism, somatization, paranoid ideation, phobic anxiety, obsessive-compulsive, and GSI indexes (all p<0.05) than those HIV-. A K-means cluster analysis identified three distinct psychiatric symptom profiles; the proportion of HIV+ was significantly greater and quality of life indicators were significantly lower in the cluster with the highest psychiatric symptom levels.

Conclusion: Higher levels of psychiatric symptoms and lower quality of life indicators among HIV+ (compared to HIV-) individuals injecting drugs support the potential importance of combining interventions that target improving psychiatric symptoms with drug treatment, particularly for HIV+ patients.

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Editor’s notes: The higher prevalence of mental health disorders among people living with HIV is well known. This paper focuses on the association of mental health disorders and HIV among people who inject drugs, in St Petersburg, Russian Federation – the city with the highest prevalence of HIV and drug use in the Russian Federation. HIV positive people who inject drugs had significantly higher prevalence of mental health problems than HIV negative people who inject drugs. They had a lower quality of life according to a validated scale, underscoring the need for strong, combination public health programmes to support this vulnerable group. The population studied was selected through existing service provision. Since these individuals were already seeking treatment on their own, there could be many more who are not engaged in care either for HIV treatment or drug use support. This suggests the need to strengthen awareness and services, especially in areas where clean needles and other risk management methods are not yet available.

Europe
Russian Federation
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