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BackgroundDaily dosing of tenofovir disoproxil fumarate, with or without emtricitabine, has high efficacy in preventing human immunodeficiency virus (HIV) infection when individuals are adherent. The target protective plasma concentration of tenofovir (TFV), however, is not fully understood. The aim of this study is to estimate the protective TFV plasma concentration.MethodsParticipant data from TFV-based daily oral and topical active arms of phase 3 trials (iPrEx, VOICE, and Partners PrEP) were pooled (n = 2950). Individual specific risk scores (low and high risk) of acquiring HIV, based on an earlier placebo analysis, were created. Longitudinal TFV pharmacokinetics (PK), HIV outcome, individual risk scores and the effect of sex at birth data were integrated and analyzed using non-linear mixed effects models.ResultsAround 50% of the individuals were estimated to be adherent, which differed from self-reported adherence (∼90%) and large variation between longitudinal adherence patterns were identified. Following oral administration, the estimated protective TFV trough concentration was substantially higher in high-risk females (45.8 ng/mL) compared with high-risk males (16.1 ng/mL) and to low-risk individuals (∼7.5 ng/mL). Dosing simulations indicated that high-risk women require full adherence to maintain protective levels.ConclusionsUsing the largest PK-HIV outcome database to date, we developed a population adherence-PK-risk-outcome model. Our results indicate that high-risk females need higher levels of plasma TFV to achieve HIV protection compared with males. HIV protection exceeds 90% in all populations if daily adherence is achieved.

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%- 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%).

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.

IntroductionCommunity-based delivery of HIV pre-exposure prophylaxis (PrEP) to South African adolescent girls and young women's (AGYW) could increase access but needs evaluation. We integrated PrEP services via home-based services and pop-up tents into existing community-based HIV testing services (CB-HTS) in Eastern Cape Province, South Africa.MethodsAfter accessing CB-HTS via a "pop-up" tent or home-based services, HIV-negative AGYW aged 16-25 years were invited to complete a baseline questionnaire and referred for PrEP services at a community-based PrEP site co-located with pop-up HTS tents. A 30-day supply of PrEP was dispensed. PrEP uptake, time-to-initiation, cohort characteristics and first medication refill within 90 days were measured using descriptive statistics.ResultsOf the 1164 AGYW who tested for HIV, 825 (74.3%) completed a questionnaire and 806 (97.7%) were referred for community-based PrEP. Of those, 624 (77.4%) presented for PrEP (482/483 [99.8%] from pop-up HTS and 142/323 [44.0%] from home-based HTS), of which 603 (96.6%) initiated PrEP. Of those initiating PrEP following home-based HTS, 59.1% initiated within 0-3 days, 25.6% within 4-14 days and 15.3% took ≥15 days to initiate; 100% of AGYW who used pop-up HTS initiated PrEP the same day. Among AGWY initiating PrEP, 37.5% had a detectable sexually transmitted infection (STI). Although AGYW reported a low self-perception of HIV risk, post-hoc application of HIV risk assessment measures to available data classified most study participants as high risk for HIV acquisition. Cumulatively, 329 (54.6%) AGYW presented for a first medication refill within 90 days of accepting their first bottle of PrEP.ConclusionsLeveraging CB-HTS platforms to provide same-day PrEP initiation and refill services was acceptable to AGYW. A higher proportion of AGYW initiated PrEP when co-located with CB-HTS sites compared to those referred following home-based HTS, suggesting that proximity of CB-HTS and PrEP services facilitates PrEP uptake among AGYW. The high prevalence of STIs among those initiating PrEP necessitates the integration of STI and HIV prevention programs for AGYW. Eligibility for PrEP initiation should not be required among AHYW in high HIV burden communities. Community-based service delivery will be crucial to maintaining access to PrEP services during the COVID-19 pandemic and future health and humanitarian emergencies.

ObjectiveVaccine-preventable human papillomavirus (HPV) infection is common, especially in sub-Saharan Africa where HIV risk is also high. However, unlike other sexually transmitted infections (STIs), HPV's role in HIV acquisition is unclear. We evaluated this relationship using data from MTN-003, a clinical trial of HIV chemoprophylaxis among cisgender women in sub-Saharan Africa.DesignA case-control study.MethodsWe matched 138 women who acquired HIV (cases) to 412 HIV-negative controls. Cervicovaginal swabs collected within 6 months before HIV seroconversion were tested for HPV DNA. We estimated the associations between carcinogenic (high-risk) and low-risk HPV types and types targeted by HPV vaccines and HIV acquisition, using conditional logistic regression models adjusted for time-varying sexual behaviors and other STIs.ResultsMean age was 23 (±4) years. Any, high-risk and low-risk HPV was detected in 84, 74 and 66% of cases, and 65, 55 and 48% of controls. Infection with at least two HPV types was common in cases (67%) and controls (49%), as was infection with nonavalent vaccine-targeted types (60 and 42%). HIV acquisition increased with any [adjusted odds ratio (aOR) 2.5, 95% confidence interval (95% CI) 1.3-4.7], high-risk (aOR 2.6, 95% CI 1.5-4.6) and low-risk (aOR 1.8, 95% CI 1.1-2.9) HPV. Each additional type detected increased HIV risk by 20% (aOR 1.2, 95% CI 1.1-1.4). HIV acquisition was associated with HPV types targeted by the nonavalent (aOR 2.1, 95% CI 1.3-3.6) and quadrivalent vaccines (aOR 1.9, 95% CI 1.1-3.2).ConclusionHPV infection is associated with HIV acquisition in sub-Saharan African women. In addition to preventing HPV-associated cancers, increasing HPV vaccination coverage could potentially reduce HIV incidence.

BackgroundIn much of eastern and southern Africa, the incidence of HIV and other sexually transmitted infections (STIs) remains high despite the scale-up of promising biomedical and behavioral interventions. Studies have documented the crucial role of transactional sex-the exchange of money, material support, or goods, in sexual relationships-and heavy alcohol use in contributing to men's and women's health outcomes. Existing policy responses to this challenge have largely focused on women, through the provision of pre-exposure prophylaxis (PrEP) or structural interventions such as education subsidies and cash transfers. However, the effectiveness of these interventions has been hindered by the relative lack of interventions and programs targeting men's behavior. We describe the protocol for a study that will test an economic intervention designed to reduce men's engagement in HIV/STI-related risk behaviors in Kenya.MethodsWe will conduct a randomized controlled trial among income-earning men in Kenya who are aged 18-39 years and self-report alcohol use and engagement in transactional sex. The study will enroll 1500 participants and randomize them to a control group or savings group. The savings group will receive access to a savings account that includes lottery-based incentives to save money regularly, opportunities to develop savings goals/strategies, and text message reminders about their savings goals. The control group will receive basic health education. Over a period of 24 months, we will collect qualitative and quantitative data from participants and a subset of their female partners. Participants will also be tested for HIV and other STIs at baseline, 12, and 24 months.DiscussionThe findings from this study have the potential to address a missing element of HIV/STI prevention efforts in sub-Saharan Africa by promoting upstream and forward-looking behavior and reducing the risk of acquiring HIV/STIs in a high HIV/STI burden setting. If this study is effective, it is an innovative approach that could be scaled up and could have great potential for scientific and public health impact in Kenya.Trial registrationClinicalTrials.gov NCT05385484 . Registered on May 23, 2022.

: Introduction: Secondary distribution of HIV self‐tests (HIVST) by HIV‐negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV). Methods: We conducted an open‐label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard‐of‐care (SOC; invitation letter to male partner for fast‐track testing). Women were followed until 12 months post‐partum. Male partners were offered confirmatory HIV testing and facilitated linkage to antiretroviral treatment (ART) or oral pre‐exposure prophylaxis (PrEP). Using intention‐to‐treat analysis, primary outcomes were male partner testing at the clinic and initiation on PrEP or ART evaluated through 12 months post‐partum (ClinicalTrials.gov, NCT03484533). Results: From November 2018 to March 2020, 500 PWLHIV were enrolled with a median age of 27 years (interquartile range [IQR] 23–30); 332 were randomized to HIVST and 168 to SOC with 437 PWLHIV (87.4%) completing 12 months follow‐up post‐partum. Of 236 male partners who tested at the clinic and enrolled (47.2%), their median age was 31 years (IQR 27–36), 45 (88.3%) men with HIV started ART and 113 (61.1%) HIV‐negative men started PrEP. There was no intervention effect on male partner testing (hazard ratio [HR] 1.04; 95% confidence interval [CI]: 0.79–1.37) or time to ART or PrEP initiation (HR 0.96; 95% CI: 0.69–1.33). Two male partners and two infants acquired HIV for an incidence of 0.99 per 100 person‐years (95% CI: 0.12–3.58) and 1.46 per 100 person‐years (95% CI: 0.18%–5.28%), respectively. Social harms related to study participation were experienced by six women (HIVST = 5, SOC = 1). Conclusions: Almost half of the partners of Ugandan PWLHIV tested for HIV with similar HIV testing rates and linkage to ART or PrEP among the secondary distribution of HIVST and SOC arms. Although half of men became aware of their HIV serostatus and linked to services, additional strategies to reach male partners of women in antenatal care are needed to increase HIV testing and linkage to services among men., INTRODUCTION Pregnant women living with HIV (PWLHIV) are more likely to achieve viral suppression (VS) and complete the prevention of mother‐to‐child HIV transmission (PMTCT) cascade when their partners are tested [...]

Introduction: UNAIDS fast track targets for ending the AIDS epidemic by 2030 call for viral suppression in 95% of people using antiretroviral therapy (ART) to treat HIV infection. Difficulties in linking to care following a positive HIV test have impeded progress towards meeting treatment targets. Community-based HIV services may reduce linkage barriers and have been associated with high retention and favourable clinical outcomes. We use qualitative data from The Delivery Optimization of Antiretroviral Therapy (DO ART) Study, a three-arm randomized trial of community ART initiation, monitoring and re-supply conducted in western Uganda and KwaZulu-Natal South Africa, to identify mechanisms through which community ART delivery may improve treatment outcomes, defined as viral suppression in people living with HIV (PLHIV). Methods: We conducted open-ended interviews with a purposeful sample of 150 DO ART participants across study arms and study sites, from October 2016 to November 2019. Interviews covered experiences of: (1) HIV testing; (2) initiating and refilling ART; and (3) participating in the DO ART Study. A combined inductive content analytic and thematic approach was used to characterize mechanisms through which community delivery of ART may have contributed to viral suppression in the DO ART trial. Results: The analysis yielded four potential mechanisms drawn from qualitative data representing the perspectives and priorities of DO ART participants. Empowering participants to schedule, re-schedule and select the locations of community-based visits via easy phone contact with clinical staff is characterized as flexibility. Integration refers to combining the components of clinic-based visits into single interaction with a healthcare provider. Providers' willingness to talk at length with participants during visits, addressing non-HIV as well as HIV-related concerns, is termed 'a slower pace'. Finally, increased efficiency denotes the time savings and increased income-generating opportunities for participants brought about by delivering services in the community. Conclusions: Understanding the mechanisms through which HIV service delivery innovations produce an effect is key to transferability and potential scale-up. The perspectives and priorities of PLHIV can indicate actionable changes for HIV care programs that may increase engagement in care and improve treatment outcomes. Keywords: delivery of healthcare; antiretroviral therapy; quality of healthcare; Uganda; South Africa; HIV, 1 | INTRODUCTION UNAIDS fast track targets for ending the AIDS epidemic by 2030 call for viral suppression in 95% of people using antiretroviral therapy (ART) to treat HIV infection [...]

: Introduction: Increased HIV testing by men in sub‐Saharan Africa is key to meeting UNAIDS 2025 testing targets. Secondary distribution of HIV self‐testing (HIVST) kits by pregnant women attending antenatal care to male partners has been shown to increase testing among African men. A detailed understanding of how women and male partners manage the distribution and use of HIVST and subsequent linkage to clinic‐based follow‐up can inform implementation and scale‐up efforts. Methods: We use qualitative data from the Obumu Study, a randomized trial of secondary distribution of HIVST by pregnant women living with HIV to male partners in Kampala, Uganda, to unpack the HIVST delivery process. The protocol included a clinic visit by male partners to confirm HIVST results. Individual interviews eliciting data on experiences of delivering and using HIVST and of subsequent linkage to clinic‐based testing were conducted with a purposefully selected sample of 45 women and 45 male partner Obumu Study participants from November 2018 to March 2021. Interview data from 59 participants (29 women and 30 men) in the HIVST arm were analysed through coding and category construction. Results: Women living with HIV were apprehensive about delivering HIVST to their partners, especially if they had not disclosed their HIV status. They invested effort in developing strategies for introducing HIVST. Male partners described a range of responses to receiving the self‐testing kit, especially fear of a positive test result. Women reported leading the self‐testing process, often conducting the test themselves. Most women confidently interpreted HIVST results. However, they tended to defer to healthcare workers rather than report positive results directly to partners. Women told their partners the testing process required a clinic follow‐up visit, often without explaining the visit's purpose. Many partners delayed the visit as a result. Women again responded by strategizing to persuade their partners to link to follow‐up care. Conclusions: Secondary distribution of HIVST by pregnant women living with HIV to male partners can be challenging, especially when women have not disclosed their HIV status. Additional support may alleviate the burden; outreach to male partners may facilitate linkage to confirmatory testing and HIV care or prevention., INTRODUCTION Increasing rates of HIV testing by men in sub‐Saharan Africa is key to meeting the UNAIDS 2025 target calling for 95% of individuals living with HIV to know their [...]

Introduction: HIV incidence remains high among African adolescent girls and young women (AGYW), who would benefit from pre-exposure prophylaxis (PrEP). Strategies to increase PrEP adherence and persistence need to be evaluated in African AGY, including incentives conditional on high adherence. Methods: The 3Ps for Prevention Study was a 12-month prospective cohort of 200 women ages 16 to 25 initiating PrEP in South Africa from 2017 to 2018. Participants received retrospective feedback about drug levels at Months 1, 2 and 3; half was randomized to receive a 200 Rand shopping voucher ($13 US) at Months 2, 3 and 4, conditioned on high intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots ([greater than or equal to]500 fmol/punch at Month 1, [greater than or equal to]700 fmol/punch at Months 2 and 3). The primary analysis was intention-to-treat, comparing the proportion with high PrEP adherence ([greater than or equal to]700 fmol/punch) at Month 3 by randomized group, based on 100% efficacy among men who have sex with men. Results: Median age of the 200 women was 19 years (interquartile range [IQR] 17, 21); 86% had a primary sexual partner. At Month 3, the mean TFV-DP level was 822 fmol/punch (SD 522) in the incentive group and 689 fmol/punch (SD 546) in the control group (p = 0.11). Forty-five (56%) of 85 women in the incentive group and 35 (41%) of 85 women in the control group had TFV-DP levels [greater than or equal to]700 fmol/punch (RR 1.35; 95% CI 0.98, 1.86; p = 0.067), which declined to 8% and 5% in the incentive and control groups at Month 12 (no significant difference by arm). 44% refilled PrEP without gaps, 14% had a gap of [greater than or equal to]3 weeks in coverage subsequently restarted PrEP and 54% accepted at the final dispensing visit at Month 9. No new HIV infections were observed after PrEP initiation. Conclusions: Among South African AGYW initiating PrEP, drug levels indicated high PrEP adherence in almost half of women at Month 3, with a non-statistically significant higher proportion with high adherence among those in the incentive group. Over half persisted with the 12-month PrEP programme although high adherence declined after Month 3. Strategies to support PrEP adherence and persistence and longer-acting PrEP formulations are needed. Keywords: HIV pre-exposure prophylaxis; adherence; drug level feedback; incentives; young women; Africa, 1 | INTRODUCTION Adolescent girls and young women (AGYW) in sub-Saharan Africa account for approximately 25% of new HIV infections globally. Recent HIV prevention trials have documented high HIV incidence [...]

: Introduction: HIV incidence remains high among African adolescent girls and young women (AGYW). The primary objective of this study is to assess pre‐exposure prophylaxis (PrEP) initiation, use, persistence and HIV acquisition among African AGYW offered PrEP in order to inform PrEP scale‐up. Methods: POWER was a prospective implementation science evaluation of PrEP delivery for sexually active HIV‐negative AGYW ages 16–25 in family planning clinics in Kisumu, Kenya and youth and primary healthcare clinics in Cape Town and Johannesburg, South Africa. Follow‐up visits occurred at month 1 and quarterly for up to 36 months. PrEP users were defined based on the month 1 refill. PrEP persistence through month 6 was assessed using Kaplan–Meier survival analysis among AGYW with a month 1 visit, defining non‐persistence as an ≥15 day gap in PrEP availability for daily dosing. PrEP execution was evaluated in a subset with PrEP supply from the prior visit sufficient for daily dosing by measuring blood tenofovir diphosphate (TFV‐DP) levels. Results: From June 2017 to September 2020, 2550 AGYW were enrolled (1000 in Kisumu, 787 in Cape Town and 763 in Johannesburg). Median age was 21 years, 66% had a sexual partner of unknown HIV status, and 29% had chlamydia and 10% gonorrhoea. Overall, 2397 (94%) initiated PrEP and 749 (31%) had a refill at 1 month. Of AGYW who could reach 6 months of post‐PrEP initiation follow‐up, 128/646 (20%) persisted with PrEP for 6 months and an additional 92/646 (14%) had a gap and restarted PrEP. TFV‐DP levels indicated that 47% (91/193) took an average of ≥4 doses/week. Sixteen HIV seroconversions were observed (incidence 2.2 per 100 person‐years, 95% CI 1.2, 3.5); 13 (81%) seroconverters either did not have PrEP dispensed in the study interval prior to seroconversion or TFV‐DP levels indicated Conclusions: In this study of PrEP integration with primary care and reproductive health services for African AGYW, demand for PrEP was high. Although PrEP use decreased in the first months, an important fraction used PrEP through 6 months. Strategies are needed to simplify PrEP delivery, support adherence and offer long‐acting PrEP options to improve persistence and HIV protection., INTRODUCTION African adolescent girls and young women (AGYW) have had HIV incidence rates of 4% in recent HIV prevention research cohorts [1–3]. Oral tenofovir‐based pre‐exposure prophylaxis (PrEP) confers >90% protection [...]

Introduction: Pre-exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means--beyond HIV prevention--for the lives of users. Methods: The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time-limited PrEP served as a 'bridge' to long-term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open-ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow-up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio-recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories. Results: Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re-establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to 'live sex' (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships. Conclusions: The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention. Clinical Trial Number: NCT02775929 Keywords: prevention; PrEP; HIV; serodiscordant couples; East Africa; demand creation, 1 | INTRODUCTION Pre-exposure prophylaxis (PrEP) has proven highly effective in preventing HIV infection when taken regularly [1-3]. Moreover, PrEP can be delivered safely, with high uptake and adherence by [...]

Background: High adherence to antiretroviral therapy (ART) is critical for achieving viral suppression and preventing onward HIV transmission. ART continuation can be challenging for pregnant women living with HIV (PWLHIV), which has critical implications for risk of vertical HIV transmission. Point-of-care viral load (POC VL) testing has been associated with improved treatment and retention outcomes. We sought to explore acceptability of POC VL testing among Ugandan PWLHIV during pregnancy and postpartum. Methods: This multimethod analysis drew on quantitative and qualitative data collected between February and December 2021. Quantitatively, we used an intent-to-treat analysis to assess whether randomization to clinic-based POC VL testing during pregnancy and infant testing at delivery was associated with improved viral suppression (≤50 copies/mL) by 3 months postpartum compared to standard-of-care (SOC) VL testing through a central laboratory, adjusting for factorial randomization for the male partner testing strategy. Additionally, a subset of 22 PWLHIV in the POC VL arm participated in in-depth qualitative interviews. We inductively analyzed transcripts to develop categories representing concepts that characterized women's perceptions of POC VL testing during pregnancy and at delivery and ways that POC VL testing may have impacted their ART adherence and viral suppression. Key themes around women's perceptions of POC VL testing were then organized into main categories. Results: Overall, 151 PWLHIV were enrolled into the study, 77 (51%) of whom were randomized to receive POC VL testing during pregnancy and at delivery. Women reported in qualitative interviews that POC VL testing had (1) motivated their ART adherence during pregnancy and postpartum and that they felt this testing method had (2) helped them protect their infants from acquiring HIV and (3) improved their emotional wellbeing. Conclusions: POC VL testing was highly acceptable among Ugandan PWLHIV and was viewed as an important tool that women believed improved their ART adherence, gave them information necessary to protect their infants from vertical HIV acquisition, and improved their emotional wellbeing. These findings support the global scale-up of POC VL testing in settings with high HIV burden, especially for PWLHIV who may be at risk of treatment disruptions or loss to follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Serodiscordant couples are a priority population for delivery of new HIV prevention interventions in Africa. An integrated strategy of delivering time-limited, oral pre-exposure prophylaxis (PrEP) to uninfected partners in serodiscordant couples as a bridge to long-term antiretroviral treatment (ART) for infected partners has been implemented in East Africa, nearly eliminating new infections. We conducted a qualitative evaluation of the integrated strategy in Uganda, to better understand its success. Methods: Data collection consisted of 274 in-depth interviews with 93 participating couples, and 55 observations of clinical encounters between couples and healthcare providers. An inductive content analytic approach aimed at understanding and interpreting couples' experiences of the integrated strategy was used to examine the data. Analysis sought to characterize: (1) key aspects of services provided; (2) what the services meant to recipients; and (3) how couples managed the integrated strategy. Themes were identified in each domain, and represented as descriptive categories. Categories were grouped inductively into more general propositions based on shared content. Propositions were linked and interpreted to explain 'why the integrated strategy worked.' Results: Couples found 'couples-focused' services provided through the integrated strategy strengthened partnered relationships threatened by the discovery of serodiscordance. They saw in services hope for 'getting help' to stay together, turned joint visits to clinic into opportunities for mutual support, and experienced counselling as bringing them closer together. Couples adopted a 'couples orientation' to the integrated strategy, considering the health of partners as they made decisions about initiating ART or accepting PrEP, and devising joint approaches to adherence. A couples orientation to services, grounded in strengthened partnerships, may have translated to greater success in using antiretrovirals to prevent HIV transmission. Conclusions: Various strategies for delivering antiretrovirals for HIV prevention are being evaluated. Understanding how and why these strategies work will improve evaluation processes and strengthen implementation platforms. We highlight the role of service organization in shaping couples' experiences of and responses to ART and PrEP in the context of the integrated strategy. Organizing services to promote positive care experiences will strengthen delivery and contribute to positive outcomes as antiretrovirals for prevention are rolled out. Keywords: HIV prevention; evaluation; mechanism of effect; service delivery; pre-exposure prophylaxis (PrEP); antiretroviral treatment (ART); implementation; Uganda, 1 | INTRODUCTION HIV serodiscordant couples--in which one partner is HIV-infected and the other uninfected--are a priority population for delivery of new HIV-prevention interventions in Africa. Oral antiretroviral medications are [...]

Introduction: Tuberculosis (TB) is the leading cause of HIV-associated mortality in Africa. As HIV testing, linkage to care and antiretroviral treatment initiation intensify to meet UNAIDS targets, it is not known what effect these efforts will have on TB detection and prevention. We aimed to characterize the TB care cascade of screening, diagnostic testing, treatment and provision of isoniazid preventive therapy (IPT) in a study of community-based HIV screening and linkage to care and determine whether symptom screening results affected progress along the cascade. Methods: Between June 2013 and March 2015, HIV-infected adults enrolled in the Linkages study, a multi-site, community-based, randomized HIV screening and linkage-to-care study in South Africa and Uganda. All participants were screened for TB symptoms at entry after testing positive for HIV and referred to local clinics for care. During the 9 month follow-up, participants were periodically surveyed about clinic linkage and initiation of HIV care as well as subsequent TB testing, treatment, or IPT. We compared outcomes between persons with and without a positive symptom screen at baseline using descriptive statistics and Poisson regression to calculate relative risks of outcomes along the care cascade. Results and discussion: Of the 1,325 HIV-infected adults enrolled, 26% reported at least one TB symptom at the time of HIV diagnosis. Loss of appetite and fever were the most commonly reported symptoms on a TB symptom screen. Despite 92% HIV linkage success, corresponding TB linkage was incomplete. Baseline TB symptoms were associated with an increased risk of a TB diagnosis (relative risk 3.23, 95% CI 1.51 to 6.91), but only 34% of symptomatic persons had sputum TB testing. Fifty-five percent of participants diagnosed with TB started TB treatment. In South Africa, only 18% of asymptomatic participants initiated IPT after linkage to HIV care, and presence of symptoms was not associated with IPT initiation (relative risk 0.86 95% CI 0.6 to 1.23). Conclusions: HIV linkage to care interventions provide an opportunity to improve completion of the TB care cascade, but will require additional support to realize full benefits. Keywords: tuberculosis; HIV; linkage; isoniazid preventive therapy, 1 | INTRODUCTION Tuberculosis (TB) is a leading cause of mortality among persons with HIV/AIDS worldwide, causing nearly a third of HIV-associated deaths [1]. Early diagnosis and treatment of active [...]

: Introduction: Among people living with HIV in South Africa, viral suppression is lower among men than women. The study aim was to test the impact of lottery incentives, which reward positive health choice (e.g. antiretroviral therapy (ART) linkage) with a chance to win a prize, on strengthening the HIV care continuum including ART initiation and viral suppression for men. Methods: We conducted a randomized, prospective trial of lottery incentives in the context of HIV testing and linkage to ART in rural KwaZulu‐Natal, South Africa. Men living with HIV were randomly allocated to: lottery incentives and motivational text messages or motivational text messages only. Lottery prize eligibility was conditional on clinic registration, ART initiation, or viral suppression by one, three and six months respectively. After completing each continuum step, participants in the lottery group were notified whether they had won and were encouraged to continue in care. Lottery prizes were either a mobile phone, data or a gift card (valued at R1000/$100). Kaplan–Meier curves were plotted to determine time to ART initiation by study group. The primary outcome was viral suppression at six months. Results: Between November 2017 and December 2018, we tested 740 men for HIV and enrolled 131 HIV‐positive men who reported not being on ART. At baseline, 100 (76%) participants were 30 years and older, 95 (73%) were unemployed and the median CD4 count was 472 cells/μL. At study exit, 84% (110/131) of participants had visited a clinic and 62% (81/131) were virally suppressed. Compared to motivational text messages, lottery incentives decreased the median time to ART initiation from 126 to 66 days (p = 0.0043, age‐adjusted Cox regression) among all participants, and, from 134 days to 20 days (p = 0.0077) among participants who were not virally suppressed at baseline. Lottery incentives had an inconclusive effect on clinic registration (RR = 1.21, 95% CI: 0.83 to 1.76) and on viral suppression at six months (RR = 1.13, 95% CI: 0.73 to 1.75) compared to motivational text messages. Conclusions: Conditional lottery incentives shortened the time to ART initiation among South African men. Behavioural economics strategies strengthen linkage to ART, but the study power was limited to see an impact on viral suppression. Clinical Trial Number: NCT03808194., INTRODUCTION Of the 4.5 million South Africans on antiretroviral therapy (ART) only a third are men, despite men making up 45% of people living with HIV nationally [1]. Viral suppression [...]

: Introduction: In South Africa, HIV‐infected men are less likely than women to test and know their status (the first UNAIDS “90‐90‐90” target), and men have worse outcomes across the HIV care cascade. HIV self‐testing (HIVST) may address this testing disparity but questions remain over the most effective distribution strategy and linkage following a positive test result. We implemented a men‐focused HIVST distribution programme to evaluate components contributing to participation and retention. Methods: We conducted an implementation study of multi‐venue HIVST kit distribution in rural and peri‐urban KwaZulu‐Natal (KZN), South Africa. We distributed HIVST kits at community points, workplaces and social venues for on site or take‐home use. Clients could choose blood‐based or oral‐fluid‐based HIVST kits and elect to watch an in‐person or video demonstration. We provided a USD2 incentive to facilitate reporting test results by phone or SMS. Persons with reactive HIVST results were provided immediate confirmatory tests (if used HIVST on site) or were referred for confirmatory testing (if took HIVST off site) and linkage to care for ART initiation. We describe the testing and linkage cascade in this sample and describe predictors of reactive HIVST results and linkage. Results: Between July and November 2018, we distributed 4496 HIVST kits in two regions of KZN (96% to men, median age 28 (IQR 23 to 35). Most participants (58%) chose blood‐based HIVST and 42% chose oral‐swab kits. 11% of men were testing for the first time. A total of 3902 (83%) of testers reported their test result to the study team, with 314 (8%) screening positive for HIV. Among 274 men with reactive HIVST results, 68% linked to ART; no significant predictors of linkage were identified. 10% of kit users reported they would prefer a different type (oral vs. blood) of kit for repeat testing than the type they used. Conclusions: HIVST is acceptable to men and rapid distribution with optional testing support is feasible in rural and peri‐urban settings. HIVST kits successfully reached younger men and identified undetected infections. Both oral and blood‐based HIVST were selected. Scaling up HIVST distribution and guidance may increase the number of first‐time testers among men and help achieve the first UNAIDS “90” for men in South Africa., INTRODUCTION In sub‐Saharan Africa, men access HIV testing and treatment services at lower rates than women [1,2]. Across the UNAIDS 90‐90‐90 cascade for HIV testing, taking ART and virological suppression [...]

: Introduction: Adolescent girls and young women (AGYW) in Africa have high HIV incidence despite scale‐up of HIV testing and HIV treatment. Placebo‐controlled trials of tenofovir‐based pre‐exposure prophylaxi (PrEP) in diverse populations demonstrated that PrEP works with close to 100% effectiveness if taken with high, but not perfect, adherence. Divergent efficacy estimates among African AGYW led to demonstration and implementation projects to better understand motivations for HIV prevention, uptake, adherence and persistence to PrEP. To inform PrEP programmes, the design and initial findings from PrEP demonstration projects for AGYW are reviewed. Discussion: Early lessons from PrEP implementation projects among young African women include: (1) awareness and demand creation with positive messaging about the benefits of PrEP are critical to motivate AGYW to consider this novel prevention technology and to foster awareness among peers, partners, parents and guardians to support AGYW's effective PrEP use; (2) PrEP initiation is high in projects that are integrating PrEP into youth‐friendly clinics, family planning clinics and mobile clinics; (3) young African women at risk are initiating PrEP, based on behavioural characteristics, history of intimate partner violence, depression and 30% prevalence of chlamydia and/or gonorrhoea; (4) provision of youth‐friendly PrEP delivery programmes that integrate reproductive health services, including contraception and the diagnosis and treatment of sexually transmitted infections, increase health impact; (5) messages that emphasize the necessity for high adherence while at potential risk of HIV exposure and support strategies that addresses AGYW's adherence challenges are essential; and, (6) a substantial proportion of AGYW do not persist with PrEP, and strategies are needed to help AGYW assess their ongoing need, motivation and challenges with persisting with PrEP. Conclusions: PrEP is feasible to implement in integrated reproductive health service delivery models to reach African AGYW. While PrEP demonstration projects indicate that women with behavioural risks and high rates of sexually transmitted diseases are initiating PrEP; effective strategies to support AGYW's adherence and persistence with PrEP are needed. Lessons learned from oral PrEP delivery, a novel first generation HIV prevention product, are relevant to longer‐acting and less adherence‐dependent strategies which are currently in clinical trials., Introduction Adolescent girls and young women (AGYW) in Africa account for approximately 25% of new HIV infections globally, and have large unmet needs for HIV prevention. African AGYW experienced high [...]