Articles tagged as "Sexual transmission and prevention"

Lies in clinical trials – the truth about data accuracy

Misreporting of product adherence in the MTN-003/VOICE trial for HIV prevention in Africa: participants' explanations for dishonesty.

Montgomery ET, Mensch B, Musara P, Hartmann M, Woeber K, Etima J, van der Straten. AIDS Behav. 2016 Nov 17. [Epub ahead of print]

Consistent over-reporting of product use limits researchers' ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that participants understood the importance of daily product use and honest reporting, yet acknowledged that research participants typically lie. Participants cited multiple reasons for misreporting adherence, including human nature, self-presentation with study staff, fear of repercussions (study termination resulting in loss of benefits and experience of HIV-related stigma), a permissive environment in which it was easy to get away with misreporting, and avoiding inconvenient additional counseling. Some participants also reported mistrust of the staff and reciprocal dishonesty about the study products. Many suggested real-time blood-monitoring during trials would encourage greater fidelity to product use and honesty in reporting. Participants at all sites understood the importance of daily product use and honesty, while also acknowledging widespread misreporting of product use. Narratives of dishonesty may suggest a wider social context of hiding products from partners and distrust about research, influenced by rumors circulating in clinic waiting-rooms and surrounding communities. Prevailing power hierarchies between staff and participants may exacerbate misreporting. Participants recognized and suggested that objective, real-time feedback is needed to encourage honest reporting.

Abstract access  

Editor’s notes: The authors of this insightful paper set out the reasons women gave in a trial of vaginal and oral programmes for inaccurately reporting their behaviour during the trial.  The authors could conduct this study because biologic/pharmacokinetic data were available which showed evidence of product use. These data were shared with individual women. None of the reasons women gave for not telling the truth is surprising. They lied to avoid additional questioning from research staff.  They feared telling the truth would result in being removed from the trial. They feared beingreprimanded. Overall, not telling the truth about product use helped them save face and time. The findings do highlight the power difference between researchers and researched, something that is hard to avoid in many areas of research. This difference was exacerbated in some circumstances by the (reported) harsh behaviour of staff towards women. The ease with which women could manipulate pill counts or product use checks, by discarding unused product is also not surprising.  The perception by some women that the researchers had lied, because of changes in the trial part way through, is important to note. This highlights the importance of clear information when a trial is explained as it begins. It also points to the importance of continuous explanations and checking participant understanding. It cannot be assumed that there is a shared understanding between researcher and researched. This is something that is easily overlooked as a trial progresses and routine visits are established. The authors highlight the value of objective measures on product use.  They also observe that some participants suggested objective, real-time feedback, during trials.  However, the authors also note that for many women lying about aspects of their lives to partners and family, was a way of managing their lives. It could be that ‘real time feedback’ would act as a deterrent to participation for some in such circumstances.  No system of data collection is perfect.  It is, however, very useful to have a timely reminder that no interview data, however collected, can be assumed to be wholly accurate.    

Africa
South Africa, Uganda, Zimbabwe
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Closing the HIV testing gap with partner-delivered self-testing

Promoting partner testing and couples testing through secondary distribution of HIV self-tests: a randomized clinical trial.

Masters SH, Agot K, Obonyo B, Napierala Mavedzenge S, Maman S, Thirumurthy H. PLoS Med. 2016 Nov 8;13(11):e1002166. doi: 10.1371/journal.pmed.1002166. eCollection 2016.

Background: Achieving higher rates of partner HIV testing and couples testing among pregnant and postpartum women in sub-Saharan Africa is essential for the success of combination HIV prevention, including the prevention of mother-to-child transmission. We aimed to determine whether providing multiple HIV self-tests to pregnant and postpartum women for secondary distribution is more effective at promoting partner testing and couples testing than conventional strategies based on invitations to clinic-based testing.

Methods and findings: We conducted a randomized trial in Kisumu, Kenya, between June 11, 2015, and January 15, 2016. Six hundred antenatal and postpartum women aged 18-39 y were randomized to an HIV self-testing (HIVST) group or a comparison group. Participants in the HIVST group were given two oral-fluid-based HIV test kits, instructed on how to use them, and encouraged to distribute a test kit to their male partner or use both kits for testing as a couple. Participants in the comparison group were given an invitation card for clinic-based HIV testing and encouraged to distribute the card to their male partner, a routine practice in many health clinics. The primary outcome was partner testing within 3 mo of enrollment. Among 570 participants analyzed, partner HIV testing was more likely in the HIVST group (90.8%, 258/284) than the comparison group (51.7%, 148/286; difference = 39.1%, 95% CI 32.4% to 45.8%, p < 0.001). Couples testing was also more likely in the HIVST group than the comparison group (75.4% versus 33.2%, difference = 42.1%, 95% CI 34.7% to 49.6%, p < 0.001). No participants reported intimate partner violence due to HIV testing. This study was limited by self-reported outcomes, a common limitation in many studies involving HIVST due to the private manner in which self-tests are meant to be used.

Conclusions: Provision of multiple HIV self-tests to women seeking antenatal and postpartum care was successful in promoting partner testing and couples testing. This approach warrants further consideration as countries develop HIVST policies and seek new ways to increase awareness of HIV status among men and promote couples testing.

Trial registration: ClinicalTrials.gov NCT02386215.

Abstract  Full-text [free] access 

Editor’s notes: Despite scale-up of HIV testing services, two in every five people living with HIV remain undiagnosed. World Health Organization (WHO) has just issued updated guidance on HIV testing services (HTS). In an effort to plug this testing gap, it strengthened the recommendation that HIV self-testing (HIVST) should be offered as one of the approaches to HTS. This paper adds to the body of evidence supporting that recommendation and provides more insight into the specific role of partner-delivered self-testing.     

There are challenges with conducting clinical trials of HIVST, one of which is selecting an appropriate outcome measure. In this trial, the primary outcome was participant report of male partner testing within three months of enrolment. Overall, uptake of male partner testing as reported by the participants was surprisingly high. It is worth noting that the participants and their partners may not have been particularly hard-to-reach groups. Almost all were married. The female participants were frequent testers. On average, they had tested three times in the past year. Most participants also reported that their male partner had tested at least once in the past year. It should also be noted that many women that were screened chose not to participate, so the participants may have to some extent pre-selected themselves as more interested and more likely to benefit from the activity.   

There were very few male partners reported as testing HIV positive during follow-up. This study was not able to determine how effectively people linked to care after HIVST. This is one of a number of research questions that remain around the delivery and impact of HIVST. Many of these are being addressed by the large HIV Self-Testing Africa (STAR) Project (http://hivstar.lshtm.ac.uk/). What seems to be beyond debate now though is that HIVST can and should play a role in helping us to achieve the UNAIDS 90-90-90 treatment target.   

Africa
Kenya
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Disbelief, stigma, ‘strong blood’ and inevitability affect seroconversion among HIV serodiscordant couples in Uganda

'People say that we are already dead much as we can still walk': a qualitative investigation of community and couples' understanding of HIV serodiscordance in rural Uganda.

Kim J, Nanfuka M, Moore D, Shafic M, Nyonyitono M, Birungi J, Galenda F, King R. BMC Infect Dis. 2016 Nov 10;16(1):665.

Background: Stable, co-habiting HIV serodiscordant couples are a key population in terms of heterosexual transmission in sub-Saharan Africa. Despite the wide availability of antiretroviral treatment and HIV educational programs, heterosexual transmission continues to drive the HIV epidemic in Africa. To investigate some of the factors involved in transmission or maintenance of serodiscordant status, we designed a study to examine participants' understanding of HIV serodiscordance and the implications this posed for their HIV prevention practices.

Methods: In-depth interviews were conducted with 28 serodiscordant couples enrolled in a treatment-as-prevention study in Jinja, Uganda. Participants were asked questions regarding sexual behaviour, beliefs in treatment and prevention, participants' and communities' understanding and context around HIV serodiscordance. Qualitative framework analysis capturing several main themes was carried out by a team of four members, and was cross-checked for consistency.

Results: It was found that most couples had difficulty explaining the phenomenon of serodiscordance and tended to be confused regarding prevention. Many individuals still held beliefs in pseudoscientific explanations for HIV susceptibility such as blood type and blood "strength". The participants' trust of treatment and medical services were well established. However, the communities' views of both serodiscordance and treatment were more pessimistic and wrought with mistrust. Stigmatization of serodiscordance and HIV-positive status were reported frequently.

Conclusions: The results indicate that despite years of treatment and prevention methods being available, stigmatization and mistrust persist in the communities of HIV-affected individuals and may directly contribute to new cases and seroconversion. We suggest that to optimize the effects of HIV treatment and prevention, clear education and support of such methods are sorely needed in sub-Saharan African communities.

Abstract  Full-text [free] access 

Editor’s notes: Expanded access to antiretroviral treatment has significantly reduced HIV-associated mortality. It has also contributed to reduced HIV incidence including in the most highly affected region of sub-Saharan Africa. Most new infections in this region are due to heterosexual transmission, with transmission within HIV serodiscordant couples in marriage or cohabitation thought to account for most new infections. This qualitative study explores the perceptions of members of HIV serodiscordant couples in terms of their understanding of serodiscordance or eventual seroconversion. The authors also explore how this understanding affects their sexual behaviour and adherence to antiretroviral therapy (for people living with HIV).

This sub-study was part of the Highly Active Antiretroviral therapy as Prevention (HAARP) study of treatment as prevention (TasP) among serodiscordant couples. In-depth interviews were conducted between June 2013 and August 2014.  All couples were initially serodiscordant upon recruitment into treatment. Over the course of the study, 14 HIV seronegative participants seroconverted. These individuals and their partners were selected for the sub-study and gender-matched to control subjects who were HIV seropositive participants whose partners did not seroconvert during the study.

The results of the HPTN 052 trial demonstrated a 96% reduction in HIV transmission within serodisordant couples associated with early use of antiretroviral therapy.  In this rural Ugandan setting, the phenomenon of serodiscordance remains poorly understood by people affected by it and the communities surrounding them. Despite extensive education campaigns and communication about HIV prevention various factors affect understanding of serodiscordance. Medication, confusion, mistrust, stigma, and a resulting sense of inevitability may negatively affect couples’ understanding and belief in the phenomenon of serodiscordance. For a variety of reasons, some serodisordant couples also report lack of consistent condom use. This is of particular concern where abstinence has proved to be an unachievable option for many couples. Improved education regarding serodiscordance and ART treatment will be required to address heterosexual transmission and ensure the maintenance of serodiscordance in affected couples.

Africa
Uganda
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School-based HIV prevention programmes appear ineffective

School-based interventions for preventing HIV, sexually transmitted infections, and pregnancy in adolescents.

Mason-Jones AJ, Sinclair D, Mathews C, Kagee A, Hillman A, Lombard C. Cochrane Database Syst Rev. 2016 Nov 8;11:CD006417.

Background: School-based sexual and reproductive health programmes are widely accepted as an approach to reducing high-risk sexual behaviour among adolescents. Many studies and systematic reviews have concentrated on measuring effects on knowledge or self-reported behaviour rather than biological outcomes, such as pregnancy or prevalence of sexually transmitted infections (STIs).

Objectives: To evaluate the effects of school-based sexual and reproductive health programmes on sexually transmitted infections (such as HIV, herpes simplex virus, and syphilis), and pregnancy among adolescents.

Search methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for published peer-reviewed journal articles; and ClinicalTrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform for prospective trials; AIDS Education and Global Information System (AEGIS) and National Library of Medicine (NLM) gateway for conference presentations; and the Centers for Disease Control and Prevention (CDC), UNAIDS, the WHO and the National Health Service (NHS) centre for Reviews and Dissemination (CRD) websites from 1990 to 7 April 2016. We hand searched the reference lists of all relevant papers.

Selection criteria: We included randomized controlled trials (RCTs), both individually randomized and cluster-randomized, that evaluated school-based programmes aimed at improving the sexual and reproductive health of adolescents.

Data collection and analysis: Two review authors independently assessed trials for inclusion, evaluated risk of bias, and extracted data. When appropriate, we obtained summary measures of treatment effect through a random-effects meta-analysis and we reported them using risk ratios (RR) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.

Main results: We included eight cluster-RCTs that enrolled 55,157 participants. Five trials were conducted in sub-Saharan Africa (Malawi, South Africa, Tanzania, Zimbabwe, and Kenya), one in Latin America (Chile), and two in Europe (England and Scotland). Sexual and reproductive health educational programmes. Six trials evaluated school-based educational interventions. In these trials, the educational programmes evaluated had no demonstrable effect on the prevalence of HIV (RR 1.03, 95% CI 0.80 to 1.32, three trials; 14 163 participants; low certainty evidence), or other STIs (herpes simplex virus prevalence: RR 1.04, 95% CI 0.94 to 1.15; three trials, 17 445 participants; moderate certainty evidence; syphilis prevalence: RR 0.81, 95% CI 0.47 to 1.39; one trial, 6977 participants; low certainty evidence). There was also no apparent effect on the number of young women who were pregnant at the end of the trial (RR 0.99, 95% CI 0.84 to 1.16; three trials, 8280 participants; moderate certainty evidence). Material or monetary incentive-based programmes to promote school attendance. Two trials evaluated incentive-based programmes to promote school attendance. In these two trials, the incentives used had no demonstrable effect on HIV prevalence (RR 1.23, 95% CI 0.51 to 2.96; two trials, 3805 participants; low certainty evidence). Compared to controls, the prevalence of herpes simplex virus infection was lower in young women receiving a monthly cash incentive to stay in school (RR 0.30, 95% CI 0.11 to 0.85), but not in young people given free school uniforms (data not pooled, two trials, 7229 participants; very low certainty evidence). One trial evaluated the effects on syphilis and the prevalence was too low to detect or exclude effects confidently (RR 0.41, 95% CI 0.05 to 3.27; one trial, 1291 participants; very low certainty evidence). However, the number of young women who were pregnant at the end of the trial was lower among those who received incentives (RR 0.76, 95% CI 0.58 to 0.99; two trials, 4200 participants; low certainty evidence). Combined educational and incentive-based programmes. The single trial that evaluated free school uniforms also included a trial arm in which participants received both uniforms and a programme of sexual and reproductive education. In this trial arm herpes simplex virus infection was reduced (RR 0.82, 95% CI 0.68 to 0.99; one trial, 5899 participants; low certainty evidence), predominantly in young women, but no effect was detected for HIV or pregnancy (low certainty evidence).

Authors' conclusions: There is a continued need to provide health services to adolescents that include contraceptive choices and condoms and that involve them in the design of services. Schools may be a good place in which to provide these services. There is little evidence that educational curriculum-based programmes alone are effective in improving sexual and reproductive health outcomes for adolescents. Incentive-based interventions that focus on keeping young people in secondary school may reduce adolescent pregnancy but further trials are needed to confirm this.

Abstract  Full-text [free] access 

Editor’s notes: School-based HIV prevention programmes are widespread worldwide. These programmes use educational institutions as a venue to reach a population that is entering sexual maturity. Several systematic reviews have found beneficial effects of these programmes on HIV-associated knowledge and behaviours, though a subsequent effect of reduced HIV incidence remains unconfirmed. In this systematic review and meta-analysis, the authors included eight randomized controlled trials from sub-Saharan Africa, Europe, and Latin America. Whether using a curriculum- or incentive-based programme, the trials did not provide evidence of an effect of school-based programmes on reducing HIV infection. Nor was there compelling evidence of an effect of these programmes on reducing sexually transmitted infection or pregnancy. This paper highlights the difficulty of translating knowledge and reported behaviors into reductions in HIV infection and other biological outcomes. Further thought is necessary to deliver effective sexual and reproductive health programmes in schools – possibly including incentives, which show some promise but need further evidence on effectiveness. 

Africa, Europe, Latin America
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Voluntary male circumcision still a cost-effective intervention in the era of 90-90-90

Impact and cost of scaling up voluntary medical male circumcision for HIV prevention in the context of the new 90-90-90 HIV treatment targets.

Kripke K, Reed J, Hankins C, Smiley G, Laube C, Njeuhmeli E. PLoS One. 2016 Oct 26;11(10):e0155734. doi: 10.1371/journal.pone.0155734. eCollection 2016.

Background: The report of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for World AIDS Day 2014 highlighted a Fast-Track Strategy that sets ambitious treatment and prevention targets to reduce global HIV incidence to manageable levels by 2020 and end the AIDS epidemic by 2030. The 90-90-90 treatment targets for 2020 call for 90% of people living with HIV to know their HIV status, 90% of people who know their status to receive treatment, and 90% of people on HIV treatment to be virally suppressed. This paper examines how scale-up of voluntary medical male circumcision (VMMC) services in four priority countries in sub-Saharan Africa could contribute to ending the AIDS epidemic by 2030 in the context of concerted efforts to close the treatment gap, and what the impact of VMMC scale-up would be if the 90-90-90 treatment targets were not completely met.

Methods: Using the Goals module of the Spectrum suite of models, this analysis modified ART (antiretroviral treatment) scale-up coverage from base scenarios to reflect the 90-90-90 treatment targets in four countries (Lesotho, Malawi, South Africa, and Uganda). In addition, a second scenario was created to reflect viral suppression levels of 75% instead of 90%, and a third scenario was created in which the 90-90-90 treatment targets are reached in women, with men reaching more moderate coverage levels. Regarding male circumcision (MC) coverage, the analysis examined both a scenario in which VMMCs were assumed to stop after 2015, and one in which MC coverage was scaled up to 90% by 2020 and maintained at 90% thereafter.

Results: Across all four countries, scaling up VMMC is projected to provide further HIV incidence reductions in addition to those achieved by reaching the 90-90-90 treatment targets. If viral suppression levels only reach 75%, scaling up VMMC leads to HIV incidence reduction to nearly the same levels as those achieved with 90-90-90 without VMMC scale-up. If only women reach the 90-90-90 targets, scaling up VMMC brings HIV incidence down to near the levels projected with 90-90-90 without VMMC scale-up. Regarding cost, scaling up VMMC increases the annual costs during the scale-up phase, but leads to lower annual costs after the MC coverage target is achieved.

Conclusions: The scenarios modeled in this paper show that the highly durable and effective male circumcision intervention increases epidemic impact levels over those of treatment-only strategies, including the case if universal levels of viral suppression in men and women are not achieved by 2020. In the context of 90-90-90, prioritizing continued successful scale-up of VMMC increases the possibility that future generations will be free not only of AIDS but also of HIV.

Abstract  Full-text [free] access 

Editor’s notes: Voluntary medical male circumcision (VMMC) has been shown to reduce the risk of female-to-male HIV transmission by up to 60%. It is a highly cost-effective HIV prevention activity. Since 2007, extensive efforts have been made to scale up VMMC in settings with high HIV prevalence and low levels of male circumcision, with the aim of reaching 80% VMMC coverage in 14 priority countries by 2016.  At the end of 2015, more than 11 million men in east and southern Africa had received VMMC.  In this modelling study, the authors look at the impact of scaling up VMMC to 90% coverage in four priority countries. The paper illustrates that VMMC scale-up can achieve additional reductions in HIV incidence above reductions achieved through testing and treatment alone. In the scenarios where the UNAIDS 90-90-90 treatment target is not completely met, VMMC scale-up can reduce HIV incidence to levels comparable to what would be achieved with the 90-90-90 treatment target. VMMC scale-up also resulted in lower long-term annual programme costs in all four settings. In 2015, UNAIDS set a target of an additional 27 million men in high-HIV prevalence settings receiving VMMC by 2021. Achieving this target will require new service delivery models, and innovative approaches to overcome current barriers that discourage men from accessing health care. VMMC is only one component in combination HIV prevention. It has advantages in being a single event that does not require ongoing adherence, offers men lifelong benefits, and is a valuable entry point for providing a broader range of health services to men including HIV testing. As this study demonstrates, VMMC remains a cost-effective strategy for reducing HIV incidence, even in the context of universal testing and treatment.  

Africa
Lesotho, Malawi, South Africa, Uganda
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Worms and HIV – time to end the debate?

Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study.

Kroidl I, Saathoff E, Maganga L, Makunde WH, Hoerauf A, Geldmacher C, Clowes P, Maboko L, Hoelscher M. Lancet. 2016 Oct 15;388(10054):1912-1920. doi: 10.1016/S0140-6736(16)31252-1. Epub 2016 Aug 3.

Background: The past decades have seen an ongoing controversial debate about whether the immune activation induced by helminths has an effect on the susceptibility of individuals to HIV. In view of this, we assessed the effect of lymphatic filariasis, a chronic helminth disease elicited by Wuchereria bancrofti, on HIV incidence in southwest Tanzania.

Methods: In this population-based cohort study, we enrolled a geographically stratified randomly chosen sample of about 10% of the households in nine distinct sites in southwest Tanzania. All household members present were followed up and tested for HIV and circulating filarial antigen, an indicator of W bancrofti adult worm burden. Our main outcome of interest was HIV incidence in participants with or without lymphatic filariasis.

Findings: Between May 29, 2006, and June 16, 2011, we enrolled 4283 households with roughly      18 000 participants. Of these, 2699 individuals from Kyela district participated in at least one round of the EMINI study. In the 1055 initially HIV-negative adolescents and adults with clearly defined lymphatic filariasis status, 32 new HIV infections were observed in 2626 person-years. HIV incidence in lymphatic filariasis-positive participants (1.91 cases per 100 person-years) was significantly higher than the incidence in lymphatic filariasis-negative participants (0.80 cases per 100 person-years). The age-adjusted and sex-adjusted incidence rate ratio was 2.17 (95% CI 1.08-4.37, p=0.0300). Lymphatic filariasis status remained an independent and significantly relevant risk factor for HIV infection when controlled for other known risk factors such as sexual behaviour and socioeconomic factors.

Interpretation: To our knowledge, this is the first prospective study demonstrating a significantly increased risk of acquiring HIV for lymphatic filariasis-infected individuals. Immunological studies and interventional treatment studies that eliminate the adult worms and not only the microfilariae are needed to follow up on the results presented.

Abstract access    

Editor’s notes: The interest in the link between helminth infections and HIV is based on our understanding of how helminth infections affect the human immune system. One core hypothesis has been that the shift to a predominantly T-helper type 2 (Th2) immune response associated with helminth infection might increase the risk of HIV acquisition. Until now, there has been no compelling evidence to support this. Observational studies looking at co-prevalence of HIV and filarial infection have not consistently illustrated an association between filarial infection and prevalent HIV infection. This relatively large population-based cohort study allowed a different approach, exploring the association between helminth infection and incident HIV infection over an average of three years follow-up. The presence of circulating filarial antigens doubled the risk of HIV acquisition.

So do the findings of this study end the debate? Perhaps not. The analysis did not account for the presence or absence of other helminth infections around the time of HIV acquisition. Also, although the analysis controlled for some socio-economic and behavioural factors known to be associated with HIV acquisition, this was incomplete so there is the possibility of residual confounding.

The findings from this study have led to renewed calls for clinical trials to evaluate the effect of antihelminthic treatment on HIV acquisition, but it may be too late. Elimination of neglected tropical diseases (including filariasis) is a global health priority in its own right, as is scale-up of combination HIV prevention strategies, including universal test and treat and pre-exposure prophylaxis. Clinical trials might therefore require unfeasibly large sample sizes to demonstrate an independent effect of antihelminthic treatment.

Africa
United Republic of Tanzania
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She looks healthy so is she dangerous to me? Unintended consequences of HIV treatment through the eyes of men in the community

They are looking just the same: antiretroviral treatment as social danger in rural Malawi.

Kaler A, Angotti N, Ramaiya A. Soc Sci Med. 2016 Oct;167:71-8. doi: 10.1016/j.socscimed.2016.08. 023. Epub 2016 Aug 18.

Research on the social impact of ART pivots on questions of individual adherence and community acceptability of treatment programmes. In this paper we examine unexpected and unintended consequences of the scale-up of treatment in rural Malawi, using a unique dataset of more than 150 observational journals from three sites, spanning 2010 to 2013, focusing on men's everyday conversations. Through thematic content analysis, we explore the emerging perception that the widespread availability of ART constitutes a form of social danger, as treatment makes it difficult to tell who does or does not have AIDS. This ambiguity introduced through ART is interpreted as putting individuals at risk, because it is no longer possible to tell who might be infected - indeed, the sick now look healthier and "plumper" than the well. This ambivalence over the social impact of ART co-exists with individual demand for and appreciation of the benefits of treatment.

Abstract access  

Editor’s notes: Widespread uptake of lifelong antiretroviral therapy means that our focus on its impact on communities should no longer be on its novelty but its consequences. This is a really interesting qualitative paper which reflects on how men in a rural community in Malawi consider the social dangers that women who are on HIV treatment, specifically, pose to men. Through the content analysis of journal entries, which captured men’s informal conversations, the researchers draw out this sub group’s ambivalence towards antiretroviral therapy. Women who have HIV can become appealing sexual partners through projecting a healthy attractiveness. Thus treatment is portrayed as disruptive by putting men, attracted to plump/ healthy women, at risk. It is revealing that two of the key tenets of current prevention policy are relatively silent within these findings. Neither the message of the prevention benefits of treatment, in which people successfully adhering to treatment pose a minimal transmission risk, nor the message that sex should be protected, because anyone’s status should be considered unknown, appears to have a significant influence on either discourse or practice. By paying attention to the ‘hum’ and ‘chatter’ of everyday life we can learn about how treatment opportunities are interpreted. We can also gain insights into how they are understood in accordance with concerns around sexual opportunities and sexual appeal. These may change but they continue to be heavily shaped by gender.  

Africa
Malawi
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Changes in sexual risk behaviour and sustained HIV incidence among MSM in the UK

Sexual behaviours, HIV testing, and the proportion of men at risk of transmitting and acquiring HIV in London, UK, 2000-13: a serial cross-sectional study.

Aghaizu A, Wayal S, Nardone A, Parsons V, Copas A, Mercey D, Hart G, Gilson R, Johnson AM. Lancet HIV. 2016 Sep;3(9):e431-40. doi: 10.1016/S2352-3018(16)30037-6. Epub 2016 Jul 14.

Background: HIV incidence in men who have sex with men (MSM) in the UK has remained unchanged over the past decade despite increases in HIV testing and antiretroviral therapy (ART) coverage. In this study, we examine trends in sexual behaviours and HIV testing in MSM and explore the risk of transmitting and acquiring HIV.

Methods: In this serial cross-sectional study, we obtained data from ten cross-sectional surveys done between 2000 and 2013, consisting of anonymous self-administered questionnaires and oral HIV antibody testing in MSM recruited in gay social venues in London, UK. Data were collected between October and January for all survey years up to 2008 and between February and August thereafter. All men older than 16 years were eligible to take part and fieldworkers attempted to approach all MSM in each venue and recorded refusal rates. Data were collected on demographic and sexual behavioural characteristics. We analysed trends over time using linear, logistic, and quantile regression.

Findings: Of 13 861 questionnaires collected between 2000 and 2013, we excluded 1985 (124 had completed the survey previously or were heterosexual reporting no anal intercourse in the past year, and 1861 did not provide samples for antibody testing). Of the 11 876 eligible MSM recruited, 1512 (13%) were HIV positive, with no significant trend in HIV positivity over time. 35% (531 of 1505) of HIV-positive MSM had undiagnosed infection, which decreased non-linearly over time from 34% (45 of 131) to 24% (25 of 106; p=0.01), while recent HIV testing (ie, in the past year) increased from 26% (263 of 997) to 60% (467 of 777; p<0.0001). The increase in recent testing in undiagnosed men (from 29% to 67%, p<0.0001) and HIV-negative men (from 26% to 62%, p<0.0001) suggests that undiagnosed infection might increasingly be recently acquired infection. The proportion of MSM reporting unprotected anal intercourse (UAI) in the past year increased from 43% (513 of 1187) to 53% (394 of 749; p<0.0001) and serosorting (exclusively) increased from 18% (207 of 1132) to 28% (177 of 6369; p<0.0001). 268 (2%) of 11 570 participants had undiagnosed HIV and reported UAI in the past year were at risk of transmitting HIV. Additionally 259 (2%) had diagnosed infection and reported UAI and non-exclusive serosorting in the past year. Although we did not collect data on antiretroviral therapy or viral load, surveillance data suggests that a small proportion of men with diagnosed infection will have detectable viral load and hence might also be at risk of transmitting HIV. 2633 (25%) of 10 364 participants were at high risk of acquiring HIV (defined as HIV-negative MSM either reporting one or more casual UAI partners in the past year or not exclusively serosorting). The proportions of MSM at risk of transmission or acquisition changed little over time (p=0.96 for MSM potentially at risk of transmission and p=0.275 for MSM at high risk of acquiring HIV). Undiagnosed men reporting UAI and diagnosed men not exclusively serosorting had consistently higher partner numbers than did other MSM over the period (median ranged from one to three across surveys in undiagnosed men reporting UAI, two to ten in diagnosed men not exclusively serosorting, and none to two in other men).

Interpretation: An increasing proportion of undiagnosed HIV infections in MSM in London might have been recently acquired, which is when people are likely to be most infectious. High UAI partner numbers of MSM at risk of transmitting HIV and the absence of a significant decrease in the proportion of men at high risk of acquiring the infection might explain the sustained HIV incidence. Implementation of combination prevention interventions comprising both behavioural and biological interventions to reduce community-wide risk is crucial to move towards eradication of HIV.

Abstract access  

Editor’s notes: Despite wide-scale ART coverage, HIV incidence among gay men and other men who have sex with men remains high in many high-income countries, and is increasing in some locations. Although expanded testing and treatment are expected to lower HIV incidence, there are concerns that changes in risk behaviour may offset the impact of ART on HIV transmission. In this paper, the authors illustrate that among gay men and other men who have sex with men in London, the proportion who had tested for HIV in the past year increased considerably over the period 2000 and 2013, with a corresponding decrease in the numbers with undiagnosed HIV.  However, there were increasing rates of condomless anal intercourse in both HIV-negative and HIV-positive men.  Furthermore, men living with HIV who were undiagnosed, and men who were not exclusively serosorting (having sex with partners of the presumed same HIV status), reported increased numbers of sexual partners over the period of the surveys. Despite the increases in recent HIV testing, three percent of men in 2013 incorrectly perceived themselves to be HIV negative. This suggests that many men who are undiagnosed may be recent infections, so could be at high risk of transmission. Previous modelling studies have illustrated that increased sexual risk behaviour, particular among people who are unaware that they are HIV positive, could account for the observed increase in incidence in gay men and other men who have sex with men. The findings of this study demonstrate the importance of core groups to the continued transmission of HIV. Test and treat programmes alone may not be sufficient to reduce HIV incidence in gay men and other men who have sex with men populations. There is the need for appropriately tailored combination prevention programmes in order to make real gains against HIV among gay men and other men who have sex with men.

Europe
United Kingdom
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Pre-exposure prophylaxis for HIV prevention is cost-effective in the Netherlands

Cost-effectiveness analysis of pre-exposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study.

Nichols BE, Boucher CA, van der Valk M, Rijnders BJ, van de Vijver DA. Lancet Infect Dis. 2016 Sep 22. pii: S1473-3099(16)30311-5. doi: 10.1016/S1473-3099(16)30311-5. [Epub ahead of print]

Background: Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation.

Methods: We developed a deterministic mathematical model, calibrated to the well-defined Dutch HIV epidemic among MSM, to predict the effect and cost-effectiveness of PrEP. PrEP was targeted to 10% of highly sexually active Dutch MSM over the coming 40 years. Cost-effectiveness ratios were calculated to predict the cost-effectiveness of daily and on-demand PrEP. Cost-effectiveness ratios below euro20 000 were considered to be cost-effective in this analysis.

Findings: Within the context of a stable HIV epidemic, at 80% effectiveness and current PrEP pricing, PrEP can cost as much as euro11 000 (IQR 9400-14 100) per quality-adjusted life-year (QALY) gained when used daily, or as little as euro2000 (IQR 1300-3000) per QALY gained when used on demand. At 80% effectiveness, daily PrEP can be considered cost-saving if the price of PrEP is reduced by 70%, and on-demand PrEP can be considered cost-saving if the price is reduced by 30-40%.

Interpretation: PrEP for HIV prevention among MSM in the Netherlands is cost-effective. The use of PrEP is most cost-effective when the price of PrEP is reduced through on-demand use or through availability of generic PrEP, and can quickly be considered cost-saving.

Abstract access  

Editor’s notes: Evidence surrounding the clinical effectiveness of pre-exposure prophylaxis to prevent HIV infection has been building for years (see HIV This Month January 2016 and February 2015).  This article now adds to the evidence with indications that pre-exposure prophylaxis is also cost-effective in a European setting.

The authors use a deterministic mathematical model to represent the HIV epidemic in the Netherlands among gay men and other men who have sex with men. They estimate the cost and cost-effectiveness of two models of pre-exposure prophylaxis usage: a daily dosage, and an ‘on demand’ dosage.  Their base case analysis found that both usage models fall under a willingness-to-pay ratio of €20 000 per QALY gained over a 40-year time horizon, although the ‘on demand’ model was least expensive at only €2000 (IQR 1300–3000) per QALY gained.  The model reflected some uncertainty around the results. However, very few results from the sensitivity analysis indicated a cost-per-QALY ratio above €20 000. Several scenarios indicated that pre-exposure prophylaxis was cost-saving. 

Pre-exposure prophylaxis was approved by the European Medicines Agency in July 2016, however it is currently not reimbursed by most European governments. This paper provides important evidence to make a case in favour of recommending reimbursement. Although the willingness-to-pay threshold used (€20 000/QALY) does not have any formal recognition in the Netherlands, several independent analyses soliciting the Dutch society’s value of a QALY reflect values much higher than this. As noted in the comment accompanying this paper (Niessen and Jaffar), the potential cost of implementing pre-exposure prophylaxis on a large-scale could be higher than current budgetary priorities allow. Still, this is an important study adding to the mounting evidence that countries should begin to consider how pre-exposure prophylaxis can be made available to people at highest risk of HIV infection.  

Europe
Netherlands
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Near elimination of HIV transmission with combined ART and PrEP

Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1-serodiscordant couples: a prospective implementation study in Kenya and Uganda.

Baeten JM, Heffron R, Kidoguchi L, Mugo NR, Katabira E, Bukusi EA, Asiimwe S, Haberer JE, Morton J, Ngure K, Bulya N, Odoyo J, Tindimwebwa E, Hendrix C, Marzinke MA, Ware NC, Wyatt MA, Morrison S, Haugen H, Mujugira A, Donnell D, Celum C. PLoS Med. 2016 Aug 23;13(8):e1002099. doi: 10.1371/journal.pmed.1002099. eCollection 2016.

Background: Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.

Methods and findings: Between November 5, 2012, and January 5, 2015, we enrolled and followed 1013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.

Conclusions: Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.

Abstract  Full-text [free] access 

Editor’s notes: Long-term follow-up of the landmark HPTN-052 trial of ART for prevention of HIV transmission between HIV serodiscordant couples was covered in a recent issue of HIV This Month. In that trial, of the few transmission events that did occur, half were during the first few months of ART use in the HIV-positive partner, before viral load suppression. This study from Kenya and Uganda now suggests that offering pre-exposure prophylaxis (PrEP) to the HIV-negative partner to bridge the gap until virologic suppression may be an effective way to almost eliminate the risk of transmission.

In this study there were significant delays in ART initiation in the HIV-positive partner. At the start of the study the recommendation for ART initiation was a CD4+ cell count <350, and only half of the HIV-positive partners had initiated ART by six months. PrEP uptake by the HIV-negative partner was high during this time period and high levels of adherence were sustained, suggesting that this was a feasible and acceptable strategy for discordant couples.

The activities were delivered using specific clinical research facilities and staff, so the logical next step would be to demonstrate scalability with delivery through routine health systems and through more innovative community-based systems.  

Africa
Kenya, Uganda
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