Articles tagged as "Sexual transmission and prevention"

Women at substantial risk of HIV infection can and should take PrEP

Editor’s notes: PrEP is now generally accepted to be one of the major reasons that the number of new infections among gay men and other men who have sex with men is falling in urban centres in Europe and the USA.  The PROUD and Ipergay randomized trials demonstrated efficacy of over 85%.  This proved conclusively that among men who were motivated to take tablets either every day or around the time of sex, PrEP could be highly effective.  The data for vaginal rather than anal sex is less straightforward.  The Partners PrEP trial and Demonstration project also showed high efficacy among both men and women in serodiscordant couples.  However, several studies among women at high risk of acquiring HIV showed no effect overall, because women were not taking the tablets for a variety of reasons.  Pharmacokinetic studies show that tenofovir-emtricitabine (the most widely used and recommended medicines for PrEP) reaches considerably higher levels in the rectal tissues than in the vagina.  As a result, we know that PrEP adherence is vital to achieve protective levels for vaginal sex, and daily dosage rather than an ‘on demand’ regimen is still recommended.  The ADAPT trial in Cape Town has now published its final results.  In this trial, young South African women were given daily PrEP in a controlled setting for four weeks before being randomized to three different regimens.  One group took PrEP every day, one group took PrEP before and after sex and the third group took two tablets each week with an additional dose after sex.  Adherence was measured using an electronic device that recorded when the pills were accessed, as well as self-report.  Drug levels were also measured.  Although this is a somewhat artificial situation involving only 59 or 60 women in each group, the results are important and confirm that for women, only daily PrEP should be recommended.  The trial also shows that women were able to adhere well, with 75% adherence and 75% of sex acts covered by PrEP among women taking the medicines every day during the follow-up period.  Neither of the other two regimens provided adequate coverage and all four incident infections occurred in these two groups (although the numbers are too small to draw reliable conclusions about the efficacy).

Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial.

Bekker LG, Roux S, Sebastien E, Yola N, Amico KR, Hughes JP, Marzinke MA, Hendrix CW, Anderson PL, Elharrar V, Stirratt M, Rooney JF, Piwowar-Manning E, Eshleman SH, McKinstry L, Li M, Dye BJ, Grant RM; HPTN 067 (ADAPT) study team. Lancet HIV. 2017 Oct 3. pii: S2352-3018(17)30156-X. doi: 10.1016/S2352-3018(17)30156-X.

Background: The relative feasibility and acceptability of daily versus non-daily dosing of oral HIV pre-exposure prophylaxis (PrEP) among women are unknown. We aimed to investigate the feasibility of non-daily PrEP regimens in adult women.

Methods: We did a randomised, open-label, phase 2 clinical trial (HPTN 067/ADAPT) of oral PrEP with emtricitabine plus tenofovir disoproxil fumarate at a research centre in Cape Town, South Africa. Participants were adult women (age ≥18 years) who received directly observed dosing once a week for 5 weeks followed by random assignment (1:1:1) at week 6 to one of three unblinded PrEP regimens for self-administered dosing over 24 weeks: daily; time-driven (twice a week plus a post-sex dose); or event-driven (one tablet both before and after sex). Primary outcomes were PrEP coverage (at least one dose within the 4 days before sex and one dose within 24 h after sex), pills needed or used to achieve regimen-specific adherence and coverage, and symptoms and side-effects. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01327651; the trial is completed, and this report presents the final analysis.

Findings: Between Sept 12, 2011, and Oct 3, 2012, 191 women were enrolled to the trial. 178 (93%) completed directly observed dosing and were randomly assigned one of the three PrEP regimens for the self-administered phase: 59 were allocated the daily regimen, 59 the time-driven regimen, and 60 the event-driven regimen. Median age of women was 26 years (IQR 21-37; range 18-52). In women allocated the daily regimen, 1459 (75%) of 1952 sex events were covered by PrEP, compared with 599 (56%) of 1074 sex events among those assigned the time-driven regimen (odds ratio [OR] 2·35, 95% CI 1·43-3·83; p=0·0007) and 798 (52%) of 1542 sex events among those allotted the event-driven regimen (2·76, 1·68-4·53; p<0·0001). Fewer pills were needed for complete adherence in women allocated non-daily regimens (vs daily regimen, relative mean 2·53 [95% CI 2·39-2·69] for the time-driven regimen and 4·16 [3·59-4·82] for the event-driven regimen; p<0·0001). Side-effects were uncommon. Eight HIV seroconversions occurred overall, with four documented during the self-administered phase (two with the time-driven regimen and two with the event-driven regimen). Adherence to the assigned regimen was 75% (7283 of 9652 doses taken) for women allocated the daily regimen compared with 65% for those assigned the time-driven regimen (2367 of 3616 doses taken; p=0·0028) and 53% for those allotted the event-driven regimen (1161 of 2203 doses taken; p<0·0001). When sex was reported in the previous week, PrEP drugs were detected (above the lower limits of quantification) more frequently in women assigned the daily regimen (73 [68%] of 107 samples) than in those allocated the time-driven regimen (42 [58%] of 72 samples) and the event-driven regimen (41 [41%] of 99 samples).

Interpretation: Daily PrEP dosing resulted in higher coverage of sex events, increased adherence to the regimen, and augmented drug concentrations than did either time-driven or event-driven dosing. These findings support recommendations for daily use of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate in women.

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Africa
South Africa
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Health economics of PrEP in Europe

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Europe
France, United Kingdom
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Efforts to understand commercial and transactional sex – involve the community and use both quantitative and qualitative methods

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

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

 

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

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

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

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

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

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

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

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

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

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

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

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

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Africa, Asia
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HIV risk – where do perception and reality overlap?

Editor’s notes: Whereas pregnancy occurs quite frequently after unprotected sex, as discussed in the previous commentary, HIV is not transmitted so easily.  In their guidance on PrEP in 2015, WHO refers to substantial risk at a level of around 3% per year, which of course means that 97% of people in that risk group do not become HIV-positive in that year.  However, risk can only be measured at a group level.  Not only does this mean that there may be unrecognized risk factors, but also at the individual level we seldom calculate a mathematical risk of something happening to us.  So a better understanding of how people perceive their risk and how this relates to their actual likelihood of becoming HIV-positive is important for many aspects of HIV prevention and behaviour change communication.  Among gay men and other men who have sex with men in Europe, Australia and the US, self-identification, combined with a few screening questions could distinguish men at very high risk for whom PrEP is an obvious choice.  Adherence in this group tends to be good and the benefits far outweigh the costs, both financial and other.

In other populations, the equation is not so straightforward.  People at lower risk of HIV may still choose to take PrEP (or use other prevention technologies in the future) but the financial costs of preventing new HIV infections will always be higher for people who adhere less and are at lower risk.  Two papers this month consider aspects of this question.  Haberer et al. considered the overlap between PrEP adherence and risky periods within the Partners Demonstration Project, in Kenya and Uganda.  In this project, serodiscordant couples were recruited and offered PrEP if they met criteria that showed that the seronegative partner had a risk of seroconversion modelled at 3-4% per year.  Thus the seronegative population as a whole was at substantial risk.  The authors then further classified those periods where the HIV-positive participant had not yet had six months of ART and the couple had not used condoms all the time as high risk.  Prevention-effective adherence was defined as taking sufficient PrEP tablets to be effective during the periods when sex could be considered high risk.  The authors found that, reassuringly, during 75% of the time periods in their study, participants should have been protected.  This helps to explain the overall high effectiveness observed in the study and suggests that in this context people make rational decisions about when to adhere to their PrEP and when they do not need to worry so much.

The study contrasts somewhat with a study from South Africa by Maughan-Brown and Venkataramani.  The authors were able to use some of the most detailed information to have been collected on perceived risk of HIV infection among participants in the Cape Area Panel Study which ran from 2002 – 2009.  Detailed questionnaires on risk perception and behaviours were collected in successive surveys.  In the final survey in 2009, HIV testing was included which allowed the authors to test whether perception of risk translated into HIV seroconversion.  Their conclusions are that perception of risk did NOT translate into actual risk.  They acknowledge that perceptions may have changed over the ensuing years but it is a cautionary study that challenges our assumptions that people who consider themselves at risk are the most likely beneficiaries of prevention efforts.  On the other hand, it is impossible to offer prevention technology to people who do not consider themselves at risk.  The challenge is to find communication and delivery systems that will encourage the perfect combination of people who are genuinely at risk, people who want to use the technology and people who will adhere to it faithfully.  A key determinant remains the costs.  Focusing on this perfect combination maximizes the cost-effectiveness of prevention technologies, but that should not preclude allowing people who want to use it to do so at their own cost.

Some potential technologies are still very expensive.  Infusions of broadly neutralizing antibodies are being tested in the Antibody Mediated Prevention (AMP) study in order to define the level and duration of protection of such a strategy.  This will help design future vaccine strategies or could be used for specific protection needs if the cost of antibody production falls.  So, the study from Sok et al. is exciting if still a long way from the field.  Until now, generating broadly neutralizing antibodies in the laboratory has proved challenging.  Standard approaches require multiple sequential immunogens to be administered to drive the antibody maturation process in rabbits or macaques, followed by purification of the relevant monoclonal antibody.  However, cows have a rather different antibody configuration, and in this study, four cows developed useful cross-clade coverage after regular boosts with just a single immunogen.  Of particular interest was the fact that the antibody response continued to evolve so that the later antibodies showed broader activity, despite no additional immunogens.  During the Paris IAS HIV Science conference, Dr Fauci foresaw a future where people living with HIV might be maintained in long-term remission without ART by regular doses of powerful antibodies possibly given subcutaneously.  Science fiction or a realistic avenue?

Finally, we need to remember that some risk factors for HIV transmission are only just being elucidated.  There has been considerable interest in the vaginal microbiome.  Women whose vaginas are largely colonized by lactobacilli are less likely to become HIV-positive, whereas women with bacterial vaginosis, or dysbiosis are more likely to.  Liu et al. have study the microbiome of the foreskin in uncircumcised men in the control arm of one of the large randomized trials of voluntary medical male circumcision in Uganda.  The authors show that men in whom they could demonstrate bacterial species such as prevotella, dialister, finegoldia, and peptoniphilus were significantly more likely to become HIV-positive on follow up than men who did not have these anaerobic microorganisms.  Furthermore, they point out that these same bacteria can be passed on to the woman, where they may also cause colonization and thus transmit an increased susceptibility to the female partner too.  The challenge is that while a simple course of antibiotics may kill the relevant organisms in both men and women, recurrence is common.  Microbiomes are an essential part of sexual and reproductive health.  Another up and coming area for research. 

 

Alignment of adherence and risk for HIV acquisition in a demonstration project of pre-exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a prospective analysis of prevention-effective adherence.

Haberer JE, Kidoguchi L, Heffron R, Mugo N, Bukusi E, Katabira E, Asiimwe S, Thomas KK, Celum C, Baeten JM. J Int AIDS Soc. 2017 Jul 25;20(1):1-9. doi: 10.7448/IAS.20.1.21842.

Introduction: Adherence is essential for pre-exposure prophylaxis (PrEP) to protect against HIV acquisition, but PrEP use need not be life-long. PrEP is most efficient when its use is aligned with periods of risk - a concept termed prevention-effective adherence. The objective of this paper is to describe prevention-effective adherence and predictors of adherence within an open-label delivery project of integrated PrEP and antiretroviral therapy (ART) among HIV serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project).

Methods: We offered PrEP to HIV-uninfected participants until the partner living with HIV had taken ART for ≥6 months (a strategy known as "PrEP as a bridge to ART"). The level of adherence sufficient to protect against HIV was estimated in two ways: ≥4 and ≥6 doses/week (per electronic monitoring). Risk for HIV acquisition was considered high if the couple reported sex with <100% condom use before six months of ART, low if they reported sex but had 100% condom use and/or six months of ART and very low if no sex was reported. We assessed prevention-effective adherence by cross-tabulating PrEP use with HIV risk and used multivariable regression models to assess predictors of ≥4 and ≥6 doses/week.

Results: A total of 985 HIV-uninfected participants initiated PrEP; 67% were male, median age was twenty-nine years, and 67% reported condomless sex in the month before enrolment. An average of ≥4 doses and ≥6 doses/week were taken in 81% and 67% of participant-visits, respectively. Adherence sufficient to protect against HIV acquisition was achieved in 75-88% of participant-visits with high HIV risk. The strongest predictor of achieving sufficient adherence was reporting sex with the study partner who was living with HIV; other statistically significant predictors included no concerns about daily PrEP, pregnancy or pregnancy intention, females aged >25 years, older male partners and desire for relationship success. Predictors of not achieving sufficient adherence were no longer being a couple, delayed PrEP initiation, >6 months of follow-up, ART use >6 months by the partner living with HIV and problem alcohol use.

Conclusions: Over three-quarters of participant-visits by HIV-uninfected partners in serodiscordant couples achieved prevention-effective adherence with PrEP. Greater adherence was observed during months with HIV risk and the strongest predictor of achieving sufficient adherence was sexual activity.

Abstract  Full-text [free] access 

 

Accuracy and determinants of perceived HIV risk among young women in South Africa.

Maughan-Brown B, Venkataramani AS. BMC Public Health. 2017 Jul 21;18(1):42. doi: 10.1186/s12889-017-4593-0.

Background: HIV risk perceptions are a key determinant of HIV testing. The success of efforts to achieve an AIDS-free generation - including reaching the UNAIDS 90-90-90 target - thus depends critically on the content of these perceptions. We examined the accuracy of HIV-risk perceptions and their correlates among young black women in South Africa, a group with one of the highest HIV incidence rates worldwide.

Methods: We used individual-level longitudinal data from the Cape Area Panel Study (CAPS) from 2005 to 2009 on black African women (20-30 years old in 2009) to assess the association between perceived HIV-risk in 2005 and the probability of testing HIV-positive four years later. We then estimated multivariable logistic regressions using cross-sectional data from the 2009 CAPS wave to assess the relationship between risk perceptions and a wide range of demographic, sexual behaviour and psychosocial covariates of perceived HIV-risk.

Results: We found that the proportion testing HIV-positive in 2009 was almost identical across perceived risk categories in 2005 (no, small, moderate, great) (χ 2 = 1.43, p = 0.85). Consistent with epidemiologic risk factors, the likelihood of reporting moderate or great HIV-risk perceptions was associated with condom-use (aOR: 0.57; 95% CI: 0.36, 0.89; p < 0.01); having ≥3 lifetime partners (aOR: 2.38, 95% CI: 1.53, 3.73; p < 0.01); knowledge of one's partner's HIV status (aOR: 0.67; 95% CI: 0.43, 1.07; p = 0.09); and being in an age-disparate partnership (aOR: 1.73; 95% CI: 1.09, 2.76; p = 0.02). However, the likelihood of reporting moderate or great self-perceived risk did not vary with sexually transmitted disease history and respondent age, both strong predictors of HIV risk in the study setting. Risk perceptions were associated with stigmatising attitudes (aOR: 0.53; 95% CI: 0.26, 1.09; p = 0.09); prior HIV testing (aOR: 0.21; 95% CI: 0.13, 0.35; p < 0.01); and having heard that male circumcision is protective (aOR: 0.38; 95% CI: 0.22, 0.64; p < 0.01).

Conclusions: Results indicate that HIV-risk perceptions are inaccurate. Our findings suggest that this inaccuracy stems from HIV-risk perceptions being driven by an incomplete understanding of epidemiological risk and being influenced by a range of psycho-social factors not directly related to sexual behaviour. Consequently, new interventions are needed to align perceived and actual HIV risk.

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Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows.

Sok D, Le KM, Vadnais M, Saye-Francisco KL, Jardine JG, Torres JL, Berndsen ZT, Kong L, Stanfield R, Ruiz J, Ramos A, Liang CH, Chen PL, Criscitiello MF, Mwangi W, Wilson IA, Ward AB, Smider VV, Burton DR. Nature. 2017 Aug 3;548(7665):108-111. doi: 10.1038/nature23301. Epub 2017 Jul 20.

No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens that antigenically mimic the HIV envelope glycoprotein (Env), such as the soluble cleaved trimer BG505 SOSIP, have improved the elicitation of potent isolate-specific antibody responses in rabbits and macaques, but so far failed to induce broadly neutralizing antibodies. One possible reason for this failure is that the relevant antibody repertoires are poorly suited to target the conserved epitope regions on Env, which are somewhat occluded relative to the exposed variable epitopes. Here, to test this hypothesis, we immunized four cows with BG505 SOSIP. The antibody repertoire of cows contains long third heavy chain complementary determining regions (HCDR3) with an ultralong subset that can reach more than 70 amino acids in length. Remarkably, BG505 SOSIP immunization resulted in rapid elicitation of broad and potent serum antibody responses in all four cows. Longitudinal serum analysis for one cow showed the development of neutralization breadth (20%, n = 117 cross-clade isolates) in 42 days and 96% breadth (n = 117) at 381 days. A monoclonal antibody isolated from this cow harboured an ultralong HCDR3 of 60 amino acids and neutralized 72% of cross-clade isolates (n = 117) with a potent median IC50 of 0.028 μg ml-1. Breadth was elicited with a single trimer immunogen and did not require additional envelope diversity. Immunization of cows may provide an avenue to rapidly generate antibody prophylactics and therapeutics to address disease agents that have evolved to avoid human antibody responses.

Abstract access  

 

Penile anaerobic dysbiosis as a risk factor for HIV infection.

Liu CM, Prodger JL, Tobian AAR, Abraham AG, Kigozi G, Hungate BA, Aziz M, Nalugoda F, Sariya S, Serwadda D, Kaul R, Gray RH, Price LB. MBio. 2017 Jul 25;8(4). pii: e00996-17. doi: 10.1128/mBio.00996-17.

Sexual transmission of HIV requires exposure to the virus and infection of activated mucosal immune cells, specifically CD4+ T cells or dendritic cells. The foreskin is a major site of viral entry in heterosexual transmission of HIV. Although the probability of acquiring HIV from a sexual encounter is low, the risk varies even after adjusting for known HIV risk factors. The genital microbiome may account for some of the variability in risk by interacting with the host immune system to trigger inflammatory responses that mediate the infection of mucosal immune cells. We conducted a case-control study of uncircumcised participants nested within a randomized-controlled trial of male circumcision in Rakai, Uganda. Using penile (coronal sulcus) swabs collected by study personnel at trial enrollment, we characterized the penile microbiome by sequencing and real-time PCR and cytokine levels by electrochemiluminescence assays. The absolute abundances of penile anaerobes at enrollment were associated with later risk of HIV seroconversion, with a 10-fold increase in Prevotella, Dialister, Finegoldia, and Peptoniphilus increasing the odds of HIV acquisition by 54 to 63%, after controlling for other known HIV risk factors. Increased abundances of anaerobic bacteria were also correlated with increased cytokines, including interleukin-8, which can trigger an inflammatory response that recruits susceptible immune cells, suggesting a mechanism underlying the increased risk. These same anaerobic genera can be shared between heterosexual partners and are associated with increased HIV acquisition in women, pointing to anaerobic dysbiosis in the genital microbiome and an accompanying inflammatory response as a novel, independent, and transmissible risk factor for HIV infection.

Importance: We found that uncircumcised men who became infected by HIV during a 2-year clinical trial had higher levels of penile anaerobes than uncircumcised men who remained HIV negative. We also found that having higher levels of penile anaerobes was also associated with higher production of immune factors that recruit HIV target cells to the foreskin, suggesting that anaerobes may modify HIV risk by triggering inflammation. These anaerobes are known to be shared by heterosexual partners and are associated with HIV risk in women. Therefore, penile anaerobes may be a sexually transmissible risk factor for HIV, and modifying the penile microbiome could potentially reduce HIV acquisition in both men and women.

Abstract  Full-text [free] access 

 

 [SC1]Unsure if this matters as they mean the same – but the guidelines literally refer to “substantial risk” which is what you also use in line 8 of the para that follows

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The case for investing in the male condom

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

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

Abstract  Full-text [free] access

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

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

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

Abstract  Full-text [free] access

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

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

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

Abstract  Full-text [free] access

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

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

Abstract

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

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

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

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

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

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

Abstract  Full-text [free] access

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

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

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

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Africa, Asia, Europe, Northern America, Oceania
Afghanistan, Angola, Australia, Azerbaijan, Bangladesh, Benin, Bolivia, Botswana, Brazil, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Congo, Côte d'Ivoire, Democratic People's Republic of Korea, Democratic Republic of the Congo, Djibouti, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, Haiti, India, Indonesia, Iran (Islamic Republic of), Iraq, Jamaica, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, Niger, Nigeria, Pakistan, Papua New Guinea, Peru, Philippines, Russian Federation, Rwanda, Sao Tome and Principe, Senegal, Sierra Leone, Solomon Islands, Somalia, South Africa, South Sudan, Sudan, Swaziland, Tajikistan, Togo, Turkmenistan, Uganda, Ukraine, United Republic of Tanzania, United States of America, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Do people take more risks when they know they are “protected”?

Editor’s notes: Risk compensation is a phenomenon well known to behavioural scientists.  When car-drivers wear seat belts, they may drive faster because they feel safer.  Despite some evidence to the contrary, a commonly voiced concern about PrEP is that people who take it will take more risks with their sexual health.  So it is reassuring to see two studies that examine partnership dynamics and condom use among people on antiretroviral therapy (ART) and among men who have been circumcised.

McGrath and Grapsa studied relationships and reported sexual behaviour among 632 people living with HIV and enrolled in an ongoing cohort study in KwaZulu Natal during the period, when only those with lower CD4 counts were eligible for ART.  They interviewed participants every 6 months, in person or by phone, for up to 36 months. This was in order to follow which relationships were formed and which dissolved and to determine how often participants were having sex and how often they were having condomless sex.  The authors clearly document (perhaps unsurprisingly) that many relationships dissolved (192 out of 565 partnerships at some time in the study) or formed (161 out of 132 individuals who were single at some time in the study).  Partnerships dissolved more frequently among people who had only been in a relationship for less than a year; people who drank alcohol and in partnerships where the participant described the relationship as being of “poor quality”.  New partners were more common for people who were younger; had not disclosed their HIV status; drank alcohol or reported having more than 3 lifetime sexual partners at the start of the study.  There was no suggestion that being on ART affected the likelihood of forming or leaving a partnership. This is important for mathematical models of HIV transmission in the era of universal treatment policies.

Sex was more frequently reported in people in more recent partnerships; people who knew their partners’ HIV status and among people who wanted more children.  Sex was less frequent and more often protected by a condom among people who did not trust their partner’s fidelity or where the couple did not live together.  People who were eligible for ART tended to use condoms more regularly during the follow up than people who were still “waiting for treatment”.  Other factors associated with more condom use included more equitable gender norms; HIV status disclosure and not living together.  Condoms were used less often in partnerships that included alcohol, partner violence or where the couple wanted more children.  Overall, the authors estimated that around 5.5% of sex acts were “risky” (that is unprotected with a partner who was HIV negative or where the HIV status was unknown) among those eligible for ART and around 13.2% for those not yet eligible.  Around one third of the participants reported having condomless sex at least once, but in almost half of these, they knew that their partner was also living with HIV.

Taking effective ART regularly means that people living with HIV are no longer infectious once their viral load is reliably suppressed.  However, it is clear that not everyone achieves viral load suppression.  This study provides useful prospective information about partnerships and sexual behaviour in the context of very high HIV transmission.  It is reassuring in showing that on the whole, sexual behaviour seems less risky, even before taking the huge effect of ART into account.  There was no evidence to suggest that risk compensation occurred in those offered ART.

In order to maximize the preventive benefits of ART, it is essential that people are supported to take their medicines regularly.  In crowded urban facilities in high prevalence settings, long waiting times, and challenges in stock management mean that people living with HIV have to be quite determined to negotiate the systems and minimize treatment interruptions.  Although it is national policy in Zambia and some other highly burden countries to provide three-month supplies to people whose HIV is stable and well controlled, McCarthy and colleagues found that less than half of people who should be getting three-month refills were doing so.  They instituted a cluster randomized trial of a quality improvement programme across 16 health facilities in Lusaka.  Each clinic follows around 4-5000 people on ART of whom around 1000 are stable and eligible for three-monthly refills.  The key element was for a focal point in each of the eight intervention clinics to be designated as a quality improvement officer and to be supported with materials to plan and monitor drug stocks and support local changes.  This is to ensure that stable patients did not have to spend long periods in the clinic or go away with less medicine than they needed.  The District Health Management team supported the quality improvement officers when the challenges identified were beyond their responsibilities or capabilities to change.  The programme led to a statistically significant 15% increase in the proportion of appropriate people receiving three-month refills (reaching 69%).  On average the intervention clinics became less congested (35 fewer visits per day compared to the controls) and had shorter waiting times (20 minutes shorter per visit) although these results did not reach statistical significance.

Another study exploring risk compensation was carried out by Shi and colleagues.  The authors used data from recent demographic and health surveys from countries that are part of the scale-up of voluntary medical male circumcision in East and Southern Africa.  Circumcision was most prevalent in Kenya (88% and 94% before and after 2008, when scale-up was pushed) and lowest in Zimbabwe (12% and 11% respectively). Overall condom usage increased in both circumcised and uncircumcised men.  Reports of condom use at last sex averaged around 15-16% before 2008 across the ten countries surveyed and rose to around 21% after 2008.  There was no suggestion that men who were circumcised were any less likely to use a condom than men who were not.  Similarly, there was no suggestion that circumcised men were more likely to have non-cohabiting partners.

The study also highlights big differences between countries, and between different groups.  Even among men with no regular partner, the use of a condom at last sex is often less than 50% with differences as expected also seen by age, education, religion and residence.  Promoting circumcision remains a hugely cost-effective approach to HIV prevention.  This study therefore provides important reassurance that the possibility of risk compensation is not serious for circumcision programmes.  Nonetheless we still have plenty of work to do to reach our targets and prevent HIV.

Does ART change partnership dynamics and HIV risk behaviours among PLWH? A cohort study in KwaZulu-Natal, South Africa.

McGrath N, Grapsa E. AIDS. 2017 Apr 10. doi: 10.1097/QAD.0000000000001502. [Epub ahead of print]

Objective: We explore the impact of antiretroviral therapy (ART) on partnership acquisition and dissolution rates and changes in sexual behaviours among HIV-infected adults.

Design: Using detailed longitudinal data from a prospective cohort of HIV-infected adults with CD4<200 cell/ml (ART-eligible) or CD4>500 cell/ml (pre-ART) conducted in rural KwaZulu-Natal, South Africa, 2009-2012.

Methods: Partnership acquisition and dissolution are explored through survival analysis methods, while generalized linear models were fitted for the sexual behaviour outcomes with interaction terms to allow the association with ART to vary over time. Throughout, the primary comparison of interest for each outcome is differences between the two ART groups.

Results: ART is not associated with partner acquisition or relationship dissolution. During follow-up, the two ART groups do not differ in the odds of being sexually active nor the number of sex acts, while the odds of unprotected sex are significantly lower for partnerships of ART-eligible participants, a0R = 0.26, 95%CI(0.15,0.43). Relationship-level characteristics including cohabitation status and wanting more children with that partner are associated with higher odds and increased frequency of sexual activity, increased odds of unprotected sex; while living with partner, higher relationship quality and longer relationship duration are associated with lower risk of partnership dissolution.

Conclusion: Being on ART was not associated with increased sexual risk behaviours, a reassuring finding given the WHO recommends ART initiation upon HIV diagnosis. The importance of relationship-level characteristics provides evidence that HIV care services should offer routine support for HIV disclosure and sexual risk reduction, and promotion of couples-testing and positive couple-relationships.

Abstract access 

Quality improvement intervention to increase adherence to ART prescription policy at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial.

McCarthy EA, Subramaniam HL, Prust ML, Prescott MR, Mpasela F, Mwango A, Namonje L, Moyo C, Chibuye B, van den Broek JW, Hehman L, Moberley S. PLoS One. 2017 Apr 18;12(4):e0175534. doi: 10.1371/journal.pone.0175534. eCollection 2017.

Introduction: In urban areas, crowded HIV treatment facilities with long patient wait times can deter patients from attending their clinical appointments and picking up their medications, ultimately disrupting patient care and compromising patient retention and adherence.

Methods: Formative research at eight facilities in Lusaka revealed that only 46% of stable HIV treatment patients were receiving a three-month refill supply of antiretroviral drugs, despite it being national policy for stable adult patients. We designed a quality improvement intervention to improve the operationalization of this policy. We conducted a cluster-randomized controlled trial in sixteen facilities in Lusaka with the primary objective of examining the intervention's impact on the proportion of stable patients receiving three-month refills. The secondary objective was examining whether the quality improvement intervention reduced facility congestion measured through two proxy indicators: daily volume of clinic visits and average clinic wait times for services.

Results: The mean change in the proportion of three-month refills among control facilities from baseline to endline was 10% (from 38% to 48%), compared to a 25% mean change (an increase from 44% to 69%) among intervention facilities. This represents a significant 15% mean difference (95% CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three-month refills. On average, control facilities had 15 more visits per day in the endline than in the baseline, while intervention facilities had 20 fewer visits per day in endline than in baseline, a mean difference of 35 fewer visits per day (P = 0.1). The change in the mean facility total wait time for intervention facilities dropped 19 minutes between baseline and endline when compared to control facilities (95% CI: -10.2-48.5; P = 0.2).

Conclusion: A more patient-centred service delivery schedule of three-month prescription refills for stable patients is viable. We encourage the expansion of this sustainable intervention in Zambia's urban clinics.

Abstract Full-text [free] access

Evidence that promotion of male circumcision did not lead to sexual risk compensation in prioritized sub-Saharan countries.

Shi CF, Li M, Dushoff J. PLoS One. 2017 Apr 25;12(4):e0175928. doi: 10.1371/journal.pone.0175928. eCollection 2017.

Background: WHO and UNAIDS prioritized 14 eastern and southern African countries with high HIV and low male circumcision prevalence for a voluntary medical male circumcision (VMMC) scale-up in 2007. Because circumcision provides only partial protection against HIV infection to men, the issue of possible risk compensation in response to VMMC campaigns is of particular concern. In this study, we looked at population-level survey data from the countries prioritized by WHO for a VMMC scale-up. We compared the difference in sexual risk behaviours (SRB) between circumcised and uncircumcised men before and after the WHO's official VMMC promotion.

Materials and Methods: Ten countries (Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe) participating in the WHO's VMMC scale-up had available data from the Demographic and Health Surveys (DHS). We used cumulative-link mixed models to investigate interactions between survey period and circumcision status in predicting SRB, in order to evaluate whether the difference between the behavior of the two groups changed before and after the scale-up, while controlling for socio-demographic and knowledge-related covariates. The main responses were condom use at last sex and number of non-cohabiting sexual partners, both in the last 12 months.

Results: There was little change in condom use by circumcised men relative to uncircumcised men from before the VMMC scale up to after the scale up. The relative odds ratio is 1.06 (95% CI, 0.95-1.18; interaction P = 0.310). Similarly, there was little change in the number of non-cohabiting partners in circumcised men (relative to uncircumcised men): the relative odds ratio of increasing the number of partners is 0.95 (95% CI, 0.86-1.05; interaction P = 0.319). Age, religion, education, job, marital status, media use and HIV knowledge also showed statistically significant association with the studied risk behaviours. We also found significant differences among countries, while controlling for covariates.

Conclusions: Overall, we find no evidence of sexual risk compensation in response to VMMC campaigns in countries prioritized by WHO. Changes in relative partner behaviour and the relative odds of condom use were small (and of uncertain sign). In fact, our estimates, though not significant, both suggest slightly less risky behavior. We conclude that sexual risk compensation in response to VMMC campaigns has not been a serious problem to date, but urge continued attention to local context, and to promulgating accurate messages about circumcision within and beyond the VMMC context.

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Africa
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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.

Abstract access 

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.

Abstract access 

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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Gender and sexuality are central considerations in voluntary medical male circumcision campaigns

Discourses of masculinity, femininity and sexuality in Uganda's Stand Proud, Get Circumcised campaign.

Rudrum S, Oliffe JL, Benoit C. Cult Health Sex. 2017 Feb;19(2):225-239. doi: 10.1080/13691058.2016.1214748. Epub 2016 Aug 11.

This paper analyses discourses of masculinity, femininity and sexuality in Stand Proud, Get Circumcised, a public health campaign promoting circumcision as an HIV-prevention strategy in Uganda. The campaign includes posters highlighting the positive reactions of women to circumcised men, and is intended to support the national rollout of voluntary medical male circumcision. We offer a critical discourse analysis of representations of masculinity, femininity and sexuality in relation to HIV prevention. The campaign materials have a playful feel and, in contrast to ABC (Abstain, Be faithful, Use condoms) campaigns, acknowledge the potential for pre-marital and extra-marital sex. However, these posters exploit male anxieties about appearance and performance, drawing on hegemonic masculinity to promote circumcision as an idealised body aesthetic. Positioning women as the campaign's face reasserts a message that women are the custodians of family health and simultaneously perpetuates a norm of estrangement between men and their health. The wives' slogan, 'we have less chance of getting HIV', is misleading, because circumcision only directly prevents female-to-male HIV transmission. Reaffirming hegemonic notions of appearance- and performance-based heterosexual masculinity reproduces existing unsafe norms about masculinity, femininity and sexuality. In selling male circumcision, the posters fail to promote an overall HIV-prevention message.

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Editor’s notes: In this article, the authors provide a feminist, critical discourse analysis of Uganda’s 2012 ‘Stand Proud, Get Circumcised’ campaign. The campaign promoted voluntary medical male circumcision as an HIV prevention strategy. The authors look at how masculinity, femininity, gender relations and acceptable sexuality are configured.

The authors note that even within this prevention strategy that is male-only, men were largely absent with women representing the campaign’s public face. They argue that this is in keeping with widespread messages about gender and HIV in the region that position women as the central actors. That said, messages about normative masculinity were evident and focussed on anxieties about men’s penises as a site for the physical assessment of masculine sexual prowess or failure. Together with a lack of reference to gay men, this positioning affirms dominant ideals of what a ‘man’ is: straight, circumcised, sexually active. The authors also observe that discourses of femininity, while departing from women-as-victims and introducing sexual pleasure, were relevant only for women’s ability to impose conditions for sex, thereby influencing men to circumcise. The authors therefore argue that the discourses around gender and sexuality, rather than being socially transformative, were instead positioned to produce existing norms around sex. This positioning offers little hope for creating structural changes to gender relations that might hinder HIV transmission. The authors also express concern that the posters sell circumcision, but neglect to highlight the evidence that women are not directly protected, or that other tools of prevention including condoms remain important. 

Africa
Uganda
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Sexual risk behaviour, HIV prevalence unchanged in Kenya as more men are circumcised

Changes in male circumcision prevalence and risk compensation in the Kisumu, Kenya population, 2008-2013.

Westercamp M, Jaoko W, Mehta S, Abuor P, Siambe P, Bailey RC. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):e30-e37. doi: 10.1097/QAI.0000000000001180.

Background: Three randomized controlled trials showed that voluntary medical male circumcision (VMMC) reduces the risk of female-to-male HIV transmission by approximately 60%. However, data from communities where VMMC programs have been implemented are needed to assess changes in circumcision prevalence and whether men and women compensate for perceived reductions in risk by increasing their HIV risk behaviors.

Methods: Scale-up of free VMMC began in Kisumu, Kenya in 2008. Between 2009 and 2013, a sequence of 3 unlinked cross-sectional surveys were conducted. All individuals 15-49 years of age residing in randomly selected households were interviewed and offered HIV testing. Male circumcision status was confirmed by examination. Design-adjusted bivariate comparisons and multivariable analyses were used for statistical inference.

Results: The prevalence of male circumcision increased from 32% (95% CI: 26% to 38%) in 2009 to 60% (95% CI: 56% to 63%) in 2013. The adjusted prevalence ratio of HIV and genital ulcer disease in circumcised compared with uncircumcised men was 0.48 (95% CI: 0.36 to 0.66) and 0.51 (95% CI: 0.37 to 0.69), respectively. There was no association between circumcision status and sexual behaviors, HIV knowledge, or indicators of risk perception.

Conclusions: The conditions necessary for the VMMC program to have a significant public health impact are present in Kisumu, Kenya. Between 2009 and 2013, circumcision prevalence increased from 30% to 60%; HIV prevalence in circumcised men was half that of uncircumcised men, and there was no or minimal sexual risk compensation.

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Editor’s notes: Evidence of the protective effect of male circumcision on HIV incidence has led many countries in sub-Saharan Africa to promote voluntary medical male circumcision (VMMC). Mathematical models have illustrated that VMMC programmes will reduce HIV prevalence over time when VMMC uptake is high, and when men who have had VMMC do not substantially increase their sexual risk behaviours. In Kenya, the VMMC programme has exceeded its targets, with over 1.1 million procedures conducted between 2008 and 2015. In this paper, the authors assessed the assumptions behind the models, using data from three population-based cross-sectional surveys conducted among male and female adult residents of Kisumu, Kenya between 2009 and 2013. During this time, VMMC prevalence among men almost doubled from 32% to 60%, yet, HIV prevalence did not change for men or women. In addition, men who had VMMC reported the same levels of sexual risk behaviours as men who were not circumcised, yet had half the prevalence of HIV and genital ulcer disease. This study re-confirms the individual benefit of VMMC in a non-trial population, while demonstrating no evidence for sexual risk compensation. This study is notable for its large sample size, population-based sampling design, visual confirmation of circumcision status, and HIV testing protocol. Studies of longer duration are required to confirm the population-level impacts of VMMC– i.e. a protection benefit beyond men who had VMMC - on HIV prevalence, and to monitor the longer-term trend in sexual risk behaviours.

Africa
Kenya
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Transwomen: high time to act

Unveiling of HIV dynamics among transgender women: a respondent-driven sampling study in Rio de Janeiro, Brazil.

Grinsztejn B, Jalil EM, Monteiro L, Velasque L, Moreira RI, Garcia AC, Castro CV, Kruger A, Luz PM, Liu AY, McFarland W, Buchbinder S, Veloso VG, Wilson EC , for the Transcender Study Team. Lancet HIV. 2017 Feb 7. pii: S2352-3018(17)30015-2. doi: 10.1016/S2352-3018(17)30015-2. [Epub ahead of print]

Background: The burden of HIV in transgender women (transwomen) in Brazil remains unknown. We aimed to estimate HIV prevalence among transwomen in Rio de Janeiro and to identify predictors of newly diagnosed HIV infections.

Methods: We recruited transwomen from Rio de Janeiro, Brazil, by respondent-driven sampling. Eligibility criteria were self-identification as transwomen, being 18 years of age or older, living in Rio de Janeiro or its metropolitan area, and having a valid peer recruitment coupon. We recruited 12 seed participants from social movements and formative focus groups who then used peer recruitment coupons to refer subsequent peers to the study. We categorised participants as HIV negative, known HIV infected, or newly diagnosed as HIV infected. We assessed predictors of newly diagnosed HIV infections by comparing newly diagnosed with HIV-negative participants. We derived population estimates with the Respondent-Driven Sampling II estimator.

Findings: Between Aug 1, 2015, and Jan 29, 2016, we enrolled 345 eligible transwomen. 29.1% (95% CI 23.2-35.4) of participants had no previous HIV testing (adjusted from 60 participants), 31.2% (18.8-43.6) had HIV infections (adjusted from 141 participants), and 7.0% (0.0-15.9) were newly diagnosed as HIV infected (adjusted from 40 participants). We diagnosed syphilis in 28.9% (18.0-39.8) of participants, rectal chlamydia in 14.6% (5.4-23.8), and gonorrhoea in 13.5% (3.2-23.8). Newly diagnosed HIV infections were associated with black race (odds ratio 22.8 [95% CI 2.9-178.9]; p=0.003), travesti (34.1 [5.8-200.2]; p=0.0001) or transsexual woman (41.3 [6.3-271.2]; p=0.0001) gender identity, history of sex work (30.7 [3.5-267.3]; p=0.002), and history of sniffing cocaine (4.4 [1.4-14.1]; p=0.01).

Interpretation: Our results suggest that transwomen bear the largest burden of HIV among any population at risk in Brazil. The high proportion of HIV diagnosis among young participants points to the need for tailored long-term health-care and prevention services to curb the HIV epidemic and improve the quality of life of transwomen in Brazil.

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Editor’s notes: This is a must-read paper for anyone interested in good participatory practices (GPP) in research and/or gender identity and HIV risk, and/or respondent driven sampling (RDS) research techniques. The researchers engaged the transwomen community from the outset in the very apt naming of the project – Transcender – and the study design – appropriate language and participant-sensitive procedures. Three community members were part of the study implementation team and the analyses were refined and written with trans community input. Although eligibility criteria included self-identification as transwomen, study participants included 131 travesti (transvestites), 107 transsexual women, 96 women, and 11 people with other gender identities. Transwomen who self-identified as women had the lowest odds of newly diagnosed HIV infection. This underscores the importance of exploring whether and how greater internal or external gender identity acceptance might confer a protective effect for HIV acquisition, perhaps through ability to use medical services through to transition, which might reduce the risk of violence. The RDS-weighted characteristics of the study participants are striking: 97% had ever experienced discrimination, 49% had ever been subjected to physical violence, and 42% had ever been raped. As for the RDS methodology itself, recruitment began with 12 seeds generating 3.6 (range two to seven) recruitment waves over a period of 26 weeks, with one seed generating 23% of the study sample. Although confidence intervals are wide, detected associations are of high magnitude and significant. With respect to homophily (the tendency to recruit others like oneself), it was moderate for HIV status and race and strong for history of sex work. Further, what are the immediate implications of the findings? Among the 29% of participants who were newly diagnosed as having HIV, nearly half reported no previous HIV testing and 44% reported a negative HIV test in the previous year. Offering pre-exposure prophylaxis (PrEP) to the latter transwomen could have prevented them from acquiring HIV. In addition to addressing the social exclusion and marginalization that creates the structural context of HIV risk for transwomen, it is critical to achieving the UNAIDS 90-90-90 treatment target that we move effectively to remove barriers to health care access. These include fighting stigma and discrimination, tackling transphobia, penalizing and preventing physical and sexual violence, and offering immediate antiretroviral therapy to people living with HIV and to offer immediate PrEP to people found to be HIV-negative.   

 

Latin America
Brazil
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