Recent outbreaks of Ebola virus (EBOV) disease (EVD) and Sudan virus (SUDV) disease (SVD) in sub-Saharan Africa underscore the ongoing public health threat posed by orthoebolaviruses. While highly effective vaccines are licensed for prevention of EVD, these offer limited cross-protection against other orthoebolaviruses, and no vaccines are licensed for SVD. Candidate SUDV vaccines are in development, but the sporadic nature of SVD outbreaks poses challenges for demonstrating clinical efficacy. In this context, it is important to consider whether and how the extensive evidence generated for EBOV infection, disease, and vaccine development can be leveraged to support SUDV vaccine development, consistent with the WHO prototype pathogen approach. Here, we synthesize available human data on the epidemiology, natural history, pathogenesis, and immunology of EBOV and SUDV infection to delineate their key similarities and differences. EBOV has caused more outbreaks, cases, and deaths than SUDV and has been more geographically widespread. There may be some differences in the typical causes of outbreaks, although gaps remain in understanding animal reservoirs for both viruses. Despite more limited data for SUDV, available evidence indicates that EBOV and SUDV share similar routes and progression of infection in humans, with comparable pathology and clinical presentation. Case fatality rates (CFRs) are generally higher for EVD than SVD. However, CFRs are influenced by outbreak context and healthcare access and should not be interpreted in isolation as evidence of intrinsic viral virulence. Collectively, this synthesis supports continued advancement of SUDV vaccine development using EBOV-informed evidence, while integrating SUDV-specific data where available.

BACKGROUND:Even within the context of antiretroviral treatment and prevention, an HIV-1 vaccine remains the best strategy for ending the HIV/AIDS epidemic. A vaccine is particularly needed in sub-Saharan Africa, where HIV-1 greatly affects people's lives and economy. Here, we aimed to assess the safety and immunogenicity of candidate T-cell vaccines in African populations. METHODS:HIV-CORE 006 was a double-blind, randomised, placebo-controlled phase 1 trial conducted across four clinical research centres in Uganda, Kenya, and Zambia. Eligible participants were not pregnant, were living without HIV-1 or HIV-2, had a low likelihood of acquiring HIV-1, were aged 18-50 years, fully comprehended the purpose and details of this study as outlined in the participant information sheet, and passed an assessment of understanding before providing written informed consent. Participants were randomly assigned (9:2) to receive either a vaccine regimen or a placebo. The vaccine was administered as ChAdOx1.tHIVconsv1 (C1) followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) in regimen C1-M3M4. The first primary outcome was the vaccines' safety assessment, assessed in all participants who received at least one vaccine or placebo dose. The second primary outcome evaluated the C1-M3M4 regimen's induction of HIVconsvX-specific T-cell responses by assessing the proportion of vaccine recipients who responded to the vaccination, assessed in all participants who received all doses of vaccine or placebo as per protocol. This study is registered with ClinicalTrials.gov, NCT04553016, and the Pan-African Clinical Trials Registry PACTR202006495409011, and is now closed. FINDINGS:Between July 15, 2021, and Nov 2, 2022, 89 healthy adults living without HIV-1 were randomly assigned, with 88 receiving either the vaccine (n=72) or placebo (n=16). Of these 88 participants, 57 (65%) were male and 31 (35%) were female. The C1, M3, and M4 vaccine components were well tolerated and induced HIVconsvX-specific responses in 70 (99%) of the 71 participants who completed all vaccine doses. Vaccine-elicited T cells peaked at a median of 2310 (IQR 1080-4480) IFN-γ spot-forming units per 106 peripheral blood mononuclear cells and recognised a median of eight (five to ten) of ten peptide pools spanning the HIVconsvX immunogen. The total frequencies of elicited T cells decreased 4·6 times over a 40-week follow-up period compared with the peak responses. Upon antigenic re-exposure, T cells proliferated, exhibited multiple effector functions, and inhibited HIV-1 representatives from clades A, B, C, and D. INTERPRETATION:Results from key sub-Saharan African populations supported the safety of the vaccine regimen previously shown in the first-in-human trial in the UK. The induction of T cells and their characteristics encourage vaccine integration into HIV-1 cure strategies, which could inform HIV-1 prevention efforts. FUNDING:The European and Developing Countries Clinical Trials Partnership.

The growing concern over participant identification in research, spurred on by flaws in conventional methods like name/date of birth-based identity cards, hospital cards and names, has led to adverse consequences, such as drug misadministration, co-enrolment and missed appointment visits. This study examines the facilitators and barriers associated with implementing biometric iris scanning for participant identification among mobile women and men working in the fishing communities of Lake Victoria. We aim to address challenges in participant identification and contribute to improved research practices. Twenty-four focus group discussions (FGDs) were conducted between 2021 and 2022 across Uganda, Kenya and Tanzania, involving participants aged 18 years and above. The study specifically targeted members of mobile fishing communities residing along the shores of Lake Victoria. The participating research organizations, all partners of the Lake Victoria Consortium for Health Research (LVCHR), operated at the four sites: Masaka and Entebbe in Uganda and Mwanza in Tanzania and Kisumu in Kenya. Each site covering two fishing communities. Participants had an experiential session with the iris camera/scanner, voluntarily undergoing the scanning process before participating in a subsequent FGD. Data collected from the FGDs were transcribed, coded, and subjected to inductive thematic analysis to identify themes directly emerging from the participants’ narratives. This methodology was employed to gain insights into the participants’ perceptions and experiences of the implementation of iris scanning technology in these communities. Overall, there was a broad acceptance of the biometric iris scanning technology, attributable to the comprehensive sensitization efforts among those who participated in the research, effective communication, and the provision of clear information regarding the intentions behind its introduction. However, because the participants had never been exposed to this technology before, various misconceptions, expectations, fears and concerns regarding privacy and safety emerged. These could potentially act as barriers to its adoption in the wider community looking beyond research participants. There is need to provide comprehensive sensitization and health education through communication channels tailored to the needs of specific communities, while engaging them is key in guiding sensitization procedures and improving acceptability. These approaches will help increase acceptability and reduce hesitancy and fears associated with the use of new technologies, such as the iris scanner.

ABSTRACT Introduction Approximately 130 000 infants acquire HIV annually despite global maternal antiretroviral therapy scale-up. We evaluated the potential clinical impact and cost-effectiveness of offering long-acting, anti-HIV broadly neutralizing antibody (bNAb) prophylaxis to infants in three distinct settings. Methods We simulated infants in Côte d’Ivoire, South Africa, and Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Pediatric (CEPAC-P) model. We modeled strategies offering a three-bNAb combination in addition to WHO-recommended standard-of-care oral prophylaxis to infants: a) with known, WHO-defined high-risk HIV exposure at birth ( HR-HIVE ); b) with known HIV exposure at birth ( HIVE ); or c) with or without known HIV exposure ( ALL ). Modeled infants received 1-dose , 2-doses , or Extended (every 3 months through 18 months) bNAb dosing. Base case model inputs included 70% bNAb efficacy (sensitivity analysis range: 10-100%), 3-month efficacy duration/dosing interval (1-6 months), and $20/dose cost ($5-$100/dose). Outcomes included pediatric HIV infections, life expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, in US$/year-of-life-saved [YLS], assuming a < 50% GDP per capita cost-effectiveness threshold). Results The base case model projects that bNAb strategies targeting HIVE and ALL infants would prevent 7-26% and 10-42% additional pediatric HIV infections, respectively, compared to standard-of-care alone, ranging by dosing approach. HIVE-Extended would be cost-effective (cost-saving compared to standard-of-care) in Côte d’Ivoire and Zimbabwe; ALL-Extended would be cost-effective in South Africa (ICER: $882/YLS). BNAb strategies targeting HR-HIVE infants would result in greater lifetime costs and smaller life expectancy gains than HIVE-Extended . Throughout most bNAb efficacies and costs evaluated in sensitivity analyses, targeting HIVE infants would be cost-effective in Côte d’Ivoire and Zimbabwe, and targeting ALL infants would be cost-effective in South Africa. Discussion Adding long-acting bNAbs to current standard-of-care prophylaxis would be cost-effective, assuming plausible efficacies and costs. The cost-effective target population would vary by setting, largely driven by maternal antenatal HIV prevalence and postpartum incidence.

Background: Recruitment and retention of participants in research studies conducted in fishing communities remain a challenge because of population mobility. Reliable and acceptable methods for identifying and tracking participants taking part in HIV prevention and treatment research are needed. The study aims to assess the acceptability, and technical feasibility of iris scans as a biometric identification method for research participants in fishing communities.Methods: This was a cross-sectional study conducted in eight fishing communities in Kenya, Tanzania, and Uganda, with follow-up after one month in a randomly selected subset of participants. All consenting participants had their iris scanned and then responded to the survey.Results: 1,199 participants were recruited. The median age was 33 [Interquartile range (IQR) 24-42] years; 56% were women. The overall acceptability of iris scanning was 99%, and the success rate was 98%. Eighty one percent (n = 949) had a successful scan on first attempt, 116 (10%) on second and 113 (9%) after more than two attempts. A month later, 30% (n = 341) of participants were followed up. The acceptability of repeat iris scanning was 99% (n = 340). All participants who accepted repeat iris scanning had successful scans, with 307 (90%) scans succeeding on first attempt; 25 (7%) on second attempt, and 8 (2%) after several attempts. The main reason for refusing iris scanning was fear of possible side effects of the scan on the eyes or body.Conclusion: The acceptability and applicability of biometric iris scan as a technique for unique identification of research participants is high in fishing communities. However, successful use of the iris scanning technology in research will require education regarding the safety of the procedure.

Background: Population mobility is a demonstrated barrier to reducing HIV incidence. A clear understanding of social networks and their influence on mobility among women in the fishing communities of Lake Victoria may contribute to tailoring effective interventions that suit the needs of these mobile women. Methods: A cross-sectional qualitative methods study was conducted to understand mobility patterns among women resident and or working in fishing communities of Lake Victoria in Kenya, Tanzania, and Uganda. The study was conducted in six fishing communities from March 2018 to June 2019. The communities were purposively selected, based on population size (1000 people or more) and HIV prevalence of > 15% among women aged 18 years or older who had lived in the fishing community for at least six months. In-depth interviews were conducted with 24 key informants and 72 women from the sites in the three countries. Questions focused on women's social networks and other factors that fuelled or facilitated women's mobility as well as challenges they faced due to mobility. Data analysis followed a thematic framework approach. Results: Different social groupings/networks existed among women in the fishing communities of Lake Victoria. These included female sex workers, women fish processors/traders, women bar workers/owners, restaurant workers, and family networks. Networks encouraged mobility, supporting finding work opportunities, but also increased sexual risks through partner changes. The benefits of networks included information sharing, financial support, and group protection, especially against violence. Conclusion: Social networks and groupings among women in the fishing communities of Lake Victoria could be useful in tailoring HIV prevention and HIV care interventions to suit the needs of these highly mobile populations.

Region-specific laboratory reference intervals (RIs) are important for clinical trials and these data are often sparse in priority areas for research, including Africa. We reviewed data on RIs from Africa to identify gaps in the literature with a systematic review of PubMed for RI studies from Africa published ≥2010. Search focus included clinical analytic chemistry, hematology, immunological parameters and RIs. Data from adults, adolescents, children, pregnant women, and the elderly were included. We excluded manuscripts reporting data from persons with conditions that might preclude clinical trial participation in studies enrolling healthy volunteers. Of 179 identified manuscripts, 80 were included in this review, covering 20 countries with the largest number of studies in Ethiopia (n = 23, 29%). Most studies considered healthy, nonpregnant adults (n = 55, 69%). Nine (11%) studies included pregnant women, 13 (16%) included adolescents and 22 (28%) included children. Recruitment, screening, enrollment procedures and definition of age strata varied across studies. The most common type of RIs reported were hematology (66, 83%); 14 studies (18%) included flow cytometry and/or T cell counts. Other common tests or panels included liver function assays (32, 40%), renal function assays (30, 38%), lipid chemistries (17, 21%) and serum electrolytes (17, 21%). The number of parameters characterized ranged from only one (three studies characterized either CD4+ counts, D-dimer, or hemoglobin), to as many as 40. Statistical methods for calculating RIs varied. 56 (70%) studies compared their results to international RI databases. Though most presented their data side-by-side with international data with little accompanying analysis, nearly all reported deviation from comparator RI data, sometimes with half or more of otherwise healthy participants having an "out of range" result. We found there is limited local RI data available in sub-Saharan Africa. Studies to fill this gap are warranted, including efforts to standardize statistical methods to derive RIs, methods to compare with other RIs, and improve representative participant selection.

The emergence of Marburg virus (MARV) in Guinea and Ghana triggered the assembly of the MARV vaccine “MARVAC” consortium representing leaders in the field of vaccine research and development aiming to facilitate a rapid response to this infectious disease threat. Here, we discuss current progress, challenges, and future directions for MARV vaccines.

AbstractBackgroundEffective, long-acting prevention approaches are needed to reduce human immunodeficiency virus (HIV) incidence. We evaluated the safety and pharmacokinetics of VRC07-523LS and PGT121 administered subcutaneously alone and in combination as passive immunization for young women in South Africa.MethodsCAPRISA 012A was a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 trial. We enrolled 45 HIV-negative women into 9 groups and assessed safety, tolerability, pharmacokinetics, neutralization activity, and antidrug antibody levels. Pharmacokinetic modeling was conducted to predict steady-state concentrations for 12- and 24-weekly dosing intervals.ResultsVRC07-523LS and PGT121, administered subcutaneously, were safe and well tolerated. Most common reactogenicity events were injection site tenderness and headaches. Nine product-related adverse events were mild and transient. Median VRC07-523LS concentrations after 20 mg/kg doses were 9.65 μg/mL and 3.86 μg/mL at 16 and 24 weeks. The median week 8 concentration after the 10 mg/kg PGT121 dose was 8.26 μg/mL. Modeling of PGT121 at 20 mg/kg showed median concentrations of 1.37 μg/mL and 0.22 μg/mL at 16 and 24 weeks. Half-lives of VRC07-523LS and PGT121 were 29 and 20 days. Both antibodies retained neutralizing activity postadministration and no antidrug antibodies were detected.ConclusionsSubcutaneous administration of VRC07-523LS in combination with optimized versions of PGT121 or other antibodies should be further assessed for HIV prevention.

We were excited to the see the publication of the JIAS Supplement entitled, "Engagement of African men and transgender women who have sex with men in HIV research." We agree with the supplement editors that attention to these populations are long overdue [1]. The title of the supplement suggested that African transgender women would be highlighted in this special issue; and we were eager to read studies about this highly under-served and under-studied population. However, as we read each article, we were deeply disappointed to find that none of them focused exclusively or even primarily on transgender women. For many years, transgender women have advocated to have their issues explored and understood separately from men who have sex with men (MSM) and other key populations. Transgender women's social contexts are distinct from MSM. They face unique challenges when accessing HIV prevention and treatment, and meetings their needs requires focused research and programming. Each of us contributed to a JIAS special issue entitled, "HIV epidemics among transgender populations: the importance of a trans-inclusive response" in 2016 [2]. In this issue, editors noted, "It cannot be overstated that transgender women are not MSM and should not be subsumed in a category that erases their identity [3]." Four years later, this special issue fails to heed that call. In 2016, Global Public Health published a series of articles describing the impact of conflating transgender women with MSM. In that issue, Poteat et al. outline issues that may be completely missed when transgender women are assumed to have the same HIV risks as MSM [4]. Perez-Brumer et al. identify how inclusion of HIV prevalence data from transgender women with MSM, artificially increases the reported prevalence among MSM as it simultaneously renders the elevated prevalence among transgender women invisible [5]. Kaplan et al. write to the limitations of Eurocentric notions of gender/sexuality and the impact on our understanding of drivers of HIV [6]. Sevelius et al. provide concrete examples from qualitative research with transgender women of the impact of conflation and erasure as a barrier to PrEP uptake among transgender women [7]. As HIV researchers who focus on the needs of transgender women in sub-Saharan Africa, we know that such research is possible and that data from studies focused on African transgender women exist. A cursory review of recent published literature and abstracts from CROI 2020 and AIDS 2020 readily identified several research studies focused on transgender women in Africa [8-11]. Meaningful inclusion of any population that appears in the title of a special issue should be a requisite. We urge JIAS to resist publishing studies that subsume transgender women within MSM-focused research. Instead, we encourage JIAS to support the publication of studies that provide transgender women with the specific attention they deserve. All authors declare no conflicts of interest. TCP conceived of the manuscript and generated the initial draft. LLAVM, JS and JK reviewed and edited the draft. All authors have read and approved the final manuscript. LLAVDM and JK are transgender community leaders who have engaged in research and advocacy to improve the health of transgender women for well over a decade. LLAVDM is based in South Africa where she leads an international organization for transgender women. JK is based in the United States where she worked in academic research and programme development for many years. Both LLAVDM and JK have generated original HIV research with transgender women as co-principal investigators. TCP and JS have conducted community-engaged research in partnership with transgender-led organizations for more than a decade.

Matt A Price,* William Kilembe, Eugene Ruzagira, Etienne Karita, Mubiana Inambao, Eduard J Sanders, Omu Anzala, Susan Allen, Vinodh A Edward, Pontiano Kaleebu, Patricia E Fast, Wasima Rida, Anatoli Kamali, Eric Hunter, Jianming Tang, Shabir Lakhi, Gaudensia Mutua, Linda Gail Bekker, Ggayi Abu-Baker, Amanda Tichacek, Paramesh Chetty, Mary H Latka, Pholo Maenetje, Heeran Makkan, Jonathan Hare, Freddie Kibengo, Fran Priddy, Elise Landais, Kundai Chinyenze and Jill Gilmour

The design of HIV prevention trials in the context of effective HIV preventive methods is a challenge. Alternate designs, including using non-randomised ‘observational control arms’ have been proposed. We used HIV simulated vaccine efficacy trials (SiVETs) to show pitfalls that may arise from using such observational controls and suggest how to conduct the analysis in the face of the pitfalls. Two SiVETs were nested within previously established observational cohorts of fisherfolk (FF) and female sex workers (FSW) in Uganda. SiVET participants received a licensed Hepatitis B vaccine in a schedule (0, 1 and 6 months) similar to that for a possible HIV vaccine efficacy trial. All participants received HIV counselling and testing every quarter for one year to assess HIV incidence rate ratio (IRR) between SiVET and non-SiVET (observational data). Propensity scores, conditional on baseline characteristics were calculated for SiVET participation and matched between SiVET and non-SiVET in the period before and during the SiVET study. We compared IRR before and after propensity score matching (PSM). In total, 3989 participants were enrolled into observational cohorts prior to SiVET, (1575 FF prior to Jul 2012 and 2414 FSW prior to Aug 2014). SiVET enrolled 572 participants (Jul 2012 to Apr 2014 in FF and Aug 2014 to Apr 2017 in FSW), with 953 non-SiVET participants observed in the SiVET concurrent period and 2928 from the pre-SiVET period (before Jul 2012 in FF or before Apr 2014 in FSW). Imbalances in baseline characteristics were observed between SiVET and non-SiVET participants in both periods before PSM. Similarly, HIV incidence was lower in SiVET than non-SiVET; SiVET-concurrent period, IRR = 0.59, 95% CI 0.31–0.68, p = 0.033 and pre-SiVET period, IRR = 0.77, 95% CI 0.43–1.29, p = 0.161. After PSM, participants baseline characteristics were comparable and there were minimal differences in HIV incidence between SiVET and non-SiVET participants. The process of screening for eligibility for efficacy trial selects participants with baseline characteristics different from the source population, confounding any observed differences in HIV incidence. Propensity score matching can be a useful tool to adjust the imbalance in the measured participants’ baseline characteristics creating a counterfactual group to estimate the effect of interventions on HIV incidence.

Many of the vaccines under development for COVID-19 involve the use of viral vectors. The Brighton Collaboration Benefit-Risk Assessment of Vaccines by Technology (BRAVATO, formerly the Viral Vector Vaccine Safety Working Group, V3SWG) working group has prepared a standardized template to describe the key considerations for the benefit-risk assessment of viral vector vaccines. This will facilitate key stakeholders to anticipate potential safety issues and interpret or assess safety data. This would also help improve communication and public acceptance of licensed viral vector vaccines.

Various long-awaited efficacy studies of vaccines and broadly neutralising antibodies for prevention of HIV are now well underway in highly endemic settings. One broadly neutralising monoclonal antibody is being assessed for proof of concept, and combinations are in the pipeline. Two multicomponent prime-and-boost vaccine regimens are being evaluated, one of which is designed for global coverage. These multicomponent vaccines present a new level of complexity that will challenge health delivery systems. We recommend that while awaiting the results, which will appear in 2020-22, the target product profiles and full public value proposition for both categories of products should be defined, and the regulatory, policy, and implementation pathways should be prepared. Economic and health benefits, cost of goods, administrative complexity, and user perspectives will be key considerations for the roll-out of effective products. Investments in manufacturing capacity and public-sector delivery systems will be needed to prepare for product introduction and scale-up. We propose a prioritisation of activities on the basis of a broad stakeholder consultation organised by WHO and UNAIDS.

Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.

Background: Outcomes in observational studies may not best estimate those expected in the HIV vaccine efficacy trials. We compared retention in Simulated HIV Vaccine Efficacy Trials (SiVETs) and observational cohorts drawn from two key populations in Uganda. Methods: Two SiVETs were nested within two observational cohorts, one in Fisherfolk (FF) and another one in Female Sex Workers (FSW). Adult participants in each observational cohort were screened for enrolment into SiVETs. Those screened-out or not screened continued participation in the observational (non-SiVET) cohorts. SiVET participants were administered a licensed hepatitis B vaccine in a schedule that mimicked an actual HIV vaccine efficacy trial. Both cohorts were followed for 12 months and retention was assessed through dropout, defined as lost to follow up, being uncontactable, refusal to continue or missing the last study clinic visit. Dropout rates were compared using Poisson models giving rate ratios and 95% confidence intervals (95%CI). Results: Out of 1,525 participants (565 FF and 960 FSW), 572 (38 %) were enrolled into SiVETs (282-FF and 290-FSW), and 953 (62%) remained in the non-SiVET cohorts. Overall, 326 (101 SiVET, 225 non-SiVET) dropped out in 1,260 Person Years of Observation (PYO), a dropout rate of 25.9 /100 PYO (95%CI: 23.2-28.8); fewer dropped out in the SiVET cohorts (18.4, 95% CI: 15.1-22.4) than in the non-SiVET cohorts (31.6, 95% CI: 27.8-36.1), rate ratio (RR) =0.58, 95% CI: 0.46-0.73. In all cohorts, the dropout was more marked in FSW than in FF population. Duration lived in community was associated with dropout in both SiVETs and religion in both non-SiVET cohorts. Conclusion: The rate of dropout was lower in SiVET compared to non-SiVET cohort. Though the difference in dropout between SiVET and non-SiVET was generally similar, the actual dropout rates were higher in the FSW population. Conduct of SiVETs in these key populations could mean that designing HIV Vaccine Efficacy Trials will benefit from lower dropout rate shown in SiVET than non-SiVET observational cohort.

Many key populations have high-risk behaviors for HIV infection making them suitable for HIV vaccine efficacy trials. However, these behaviors may change when participants enroll into a trial. We used HIV simulated vaccine efficacy trials (SiVETs) nested within observational cohorts of fisherfolks and female sex workers in Uganda to evaluate this difference. We screened observational cohort participants for enrolment into SiVETs, until 572 were enrolled. Those not enrolled (n = 953) continued participation in the observational cohorts. We determined risk behaviors at baseline and at 1 year, assigned a numeric score to each behavior and defined composite score as the sum of reported behaviors. We compared changes in scores over 12 months. Both observational cohorts and SiVETs saw a significant decrease in score but greatest in the SiVETs. Investigators recruiting for trials from these populations should consider the likely effect of reduction in risk behaviors on incident HIV infection and trial statistical power.