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IntroductionAchieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan Africa (SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign.DiscussionThese three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved >90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted in marked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in which mortality was comprehensively measured.ConclusionsThese trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets.

Background Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial randomised 14 communities to receive the 'PopART' intervention during 2014 to 2017 (7 arm A and 7 arm B communities) and 7 communities to receive standard-of-care (arm C). The intervention was delivered door-to-door by community HIV care providers (CHiPs) and included universal HIV testing, facilitated linkage to HIV care at government health clinics, and systematic TB symptom screening. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study aimed to measure the impact of delivering the PopART intervention on TB outcomes, in communities with high HIV and TB prevalence. Methods and findings The study population of the HPTN 071 (PopART) trial included individuals aged [greater than or equal to]15 years living in 21 urban and peri-urban communities in Zambia and South Africa, with a total population of approximately 1 million and an adult HIV prevalence of around 15% at the time of the trial. Two sputum samples for TB testing were provided to CHiPs by individuals who reported [greater than or equal to]1 TB suggestive symptom (a cough for [greater than or equal to]2 weeks, unintentional weight loss [greater than or equal to]1.5 kg in the last month, or current night sweats) or that a household member was currently on TB treatment. Antiretroviral therapy (ART) was offered universally at clinics in arm A and according to local guidelines in arms B and C. The TREATS study was conducted in the same 21 communities as the HPTN 071 (PopART) trial between 2017 and 2022, and TB prevalence was a co-primary endpoint of the TREATS study. The primary comparison was between the PopART intervention (arms A and B combined) and the standard-of-care (arm C). During 2019 to 2021, a TB prevalence survey was conducted among randomly selected individuals aged [greater than or equal to]15 years (approximately 1,750 per community in arms A and B, approximately 3,500 in arm C). Participants were screened on TB symptoms and chest X-ray, with diagnostic testing using Xpert-Ultra followed by culture for individuals who screened positive. Sputum eligibility was determined by the presence of a cough for [greater than or equal to]2 weeks, or [greater than or equal to]2 of 5 'TB suggestive' symptoms (cough, weight loss for [greater than or equal to]4 weeks, night sweats, chest pain, and fever for [greater than or equal to]2 weeks), or chest X-ray CAD4TBv5 score [greater than or equal to]50, or no available X-ray results. TB prevalence was compared between trial arms using standard methods for cluster-randomised trials, with adjustment for age, sex, and HIV status, and multiple imputation was used for missing data on prevalent TB. Among 83,092 individuals who were eligible for the survey, 49,556 (59.6%) participated, 8,083 (16.3%) screened positive, 90.8% (7,336/8,083) provided 2 sputum samples for Xpert-Ultra testing, and 308 (4.2%) required culture confirmation. Overall, estimated TB prevalence was 0.92% (457/49,556). The geometric means of 7 community-level prevalence estimates were 0.91%, 0.70%, and 0.69% in arms A, B, and C, respectively, with no evidence of a difference comparing arms A and B combined with arm C (adjusted prevalence ratio 1.14, 95% confidence interval, CI [0.67, 1.95], p = 0.60). TB prevalence was higher among people living with HIV than HIV-negative individuals, with an age-sex-community adjusted odds ratio of 2.29 [95% CI 1.54, 3.41] in Zambian communities and 1.61 [95% CI 1.13, 2.30] in South African communities. The primary limitations are that the study was powered to detect only large reductions in TB prevalence in the intervention arm compared with standard-of-care, and the between-community variation in TB prevalence was larger than anticipated. Conclusions There was no evidence that the PopART intervention reduced TB prevalence. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of several years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB. Trial registration The TREATS study was registered with ClinicalTrials.gov Identifier: NCT03739736 on November 14, 2018. The HPTN 071 (PopART) trial was registered at ClinicalTrials.gov under number NCT01900977 on July 17, 2013., Author(s): Eveline Klinkenberg 1,2,3,*, Sian Floyd 1,*, Kwame Shanaube 4, Linda Mureithi 5, Thomas Gachie 1,4, Petra de Haas 3, Barry Kosloff 1,4, Peter J. Dodd 6, Maria Ruperez 1, [...]

Introduction: The HPTN 071 (PopART) trialdemonstrated that universalHIV testing-and-treatment reduced community-level HIV incidence. Door-to-door delivery of HIV testing services (HTS) was one of the main components of the intervention. From an early stage, men were less likely to know their HIV status than women, primarily because they were not home during service delivery. To reach more men, different strategies were implemented during the trial. We present the relative contribution of these strategies to coverage of HTS and the impact of community hubs implemented after completion of the trial among men. Methods: Between 2013 and 2017, three intervention rounds (IRs) of door-to-door HTS delivery were conducted in eight PopART communities in Zambia. Additionalstrategies implemented in parallel, included: community-wide 'Man-up' campaigns (IR1), smaller HTS campaigns at work/socialplaces (IR2) and revisits to households with the option of HIV self-testing (HIVST) (IR3). In 2018, community 'hubs' offering HTS were implemented for 7 months in alleight communities. Population enumeration data for each round of HTS provided the denominator, allowing for calculation of the proportion of men tested as a result of each strategy during different time periods. Results: By the end of the three IRs, 65-75% of men were reached with HTS, primarily through door-to-door service delivery. In IR1 and IR2, 'Man-up' and work/socialplace campaigns accounted for ~1 percentage point each and in IR3, revisits with the option of self-testing for ~15 percentage points of this totalcoverage per IR. The yield of newly diagnosed HIV-positive men ranged from 2.2% for HIVST revisits to 9.9% in work/socialplaces. At community hubs, the majority of visitors accepting services were men (62.8%). In total, we estimated that ~36% (2.2% tested HIV positive) of men resident but not found at their household during IR3 of PopART accessed HTS provided at the hubs after trial completion. Conclusions: Achieving high coverage of HTS among men requires universal, home-based service delivery combined with an option of HIVST and delivery of HTS through community-based hubs. When men are reached, they are willing to test for HIV Reaching men thus requires implementers to adapt their HTS delivery strategies to meet men's needs. Clinical Trial Number: NCT01900977 Keywords: men; HIV testing; Zambia; sub-Saharan Africa; community-based, 1 | INTRODUCTION Data from sub-Saharan African countries consistently show that men are less likely than women to test for HIV [1-3]. In Zambia, the 2013-14 Demographic and Health Survey [...]

Background The growing population of adolescents and young people (AYP) aged 15 to 24 in sub-Saharan Africa face a high burden of HIV in many settings. Unintended pregnancies among adolescent girls in the region remain high. Nonetheless, the sexual and reproductive health (SRH) service needs of AYP have remained underserved. We conducted a cluster-randomised trial (CRT) to estimate the impact of community-based, peer-led SRH service provision on knowledge of HIV status and other SRH outcomes, including met need for contraceptives. Methods and findings Yathu Yathu was a cluster-randomised trial (CRT) conducted from 2019 to 2021 in 2 urban communities in Lusaka, Zambia. The communities were divided into 20 zones (approximately 2,350 AYP/zone) that were randomly allocated to the Yathu Yathu intervention or control arm. In each intervention zone, a community-based hub, staffed by peer support workers, was established to provide SRH services. In 2019, a census was conducted in all zones; all consenting AYP aged 15 to 24 were given a Yathu Yathu card, which allowed them to accrue points for accessing SRH services at the hub and health facility (intervention arm) or the health facility only (control arm). Points could be exchanged for rewards, thus acting as an incentive to use SRH services in both arms. We conducted a cross-sectional survey in 2021 to estimate the impact of Yathu Yathu on the primary outcome: knowledge of HIV status (self-reporting living with HIV or HIV testing in the last 12 months) and secondary outcomes, including use of pre-exposure prophylaxis (PrEP) in the last 12 months, current use of antiretroviral therapy (ART), and met need for contraceptive services. The sampling was stratified on sex and age group, and we analysed data at cluster-level using a two-stage process recommended for CRTs with Conclusions Delivering community-based, peer-led SRH services increased knowledge of HIV status among AYP, both males and females, compared with the control arm. Scaling up the highly effective Yathu Yathu strategy has the potential to make a substantial contribution to increasing access to HIV prevention and care services for young people. However, additional implementation research is needed to understand how to improve uptake of broader SRH services, beyond uptake of HIV testing. Trial registration ISRCTN75609016, clinicaltrials.gov number NCT04060420, Author(s): Bernadette Hensen 1,2,*, Sian Floyd 3, Mwelwa M. Phiri 4, Ab Schaap 3,4, Lucheka Sigande 4, Melvin Simuyaba 4, Lawrence Mwenge 4, Rosemary Zulu-Phiri 4, Louis Mwape 4, Sarah [...]

DesignUniversal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa. This report describes and contrasts the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials.MethodsWe conducted a comparative assessment of the five trials using data extracted from study protocols and collected during baseline studies, with additional input from study investigators. We organized differences and commonalities across the trials in five categories: trial contexts, research designs, intervention packages, trial themes and adaptations.ResultsAll performed in the context of generalized HIV epidemics, the trials highly differ in their social, demographic, economic, political and health systems settings. They share the common aim of assessing the impact of UTT on the HIV epidemic but differ in methodological aspects such as study design and eligibility criteria for trial populations. In addition to universal ART initiation, the trials deliver a wide range of biomedical, behavioural and structural interventions as part of their UTT strategies. The five studies explore common issues, including the uptake rates of the trial services and individual health outcomes. All trials have adapted since their initiation to the evolving political, economic and public health contexts, including adopting the successive national recommendations for ART initiation.ConclusionsWe found substantial commonalities but also differences between the five UTT trials in their design, conduct and multidisciplinary outputs. As empirical literature on how UTT may improve efficiency and quality of HIV care at population level is still scarce, this article provides a foundation for more collaborative research on UTT and supports evidence-based decision making for HIV care in country and internationally.

: Introduction: Universal HIV testing and treatment (UTT) has individual and public health benefits. HPTN 071 (PopART), a community‐randomized trial in Zambia and South Africa, demonstrated that UTT decreased HIV incidence. This endpoint was assessed in a cohort of >48,000 randomly selected adults in the study communities. We evaluated the impact of UTT on HIV drug resistance in this cohort and compared other resistance‐related outcomes in participants with recent versus non‐recent HIV infection. Methods: Two years after the start of HPTN 071 (2016–2017), 6259 participants were HIV positive and 1902 were viremic (viral load >400 copies/ml). HIV genotyping and antiretroviral (ARV) drug testing were performed for viremic participants in three groups: seroconverters (infected 1 year, random subset) and participants with unknown duration of infection (random subset). A two‐stage cluster‐based approach was used to assess the impact of the study intervention on drug resistance. Treatment failure was defined as being viremic with ARV drugs detected. Participants were classified as ARV naïve based on self‐report and ARV drug testing. Results: Genotyping results were obtained for 758 participants (143 seroconverters; 534 non‐seroconverters; and 81 unknown duration of infection). The estimated prevalence of resistance in the study communities was 37% for all viremic persons and 11% for all HIV‐positive persons. There was no association between UTT and drug resistance. Resistance was detected in 14.0% of seroconverters and 40.8% of non‐seroconverters (non‐nucleoside reverse transcriptase inhibitor resistance: 14.0% and 39.9%; nucleoside/nucleotide reverse transcriptase inhibitor resistance: 0.7% and 15.5%; protease inhibitor resistance: 0% and 1.9%; multi‐class resistance: 0.7% and 16.1%, respectively). ARV drugs were detected in 2/139 (1.4%) of seroconverters and 94/534 (17.6%) of non‐seroconverters tested. These participants were classified as failing ART; 88 (93.6%) of the non‐seroconverters failing ART had resistance. Mutations used for surveillance of transmitted drug resistance were detected in 10.5% of seroconverters and 15.1% of non‐seroconverters who were ARV naive. Conclusions: UTT was not associated with an increase in drug resistance in this cohort. Higher rates of drug resistance and multi‐class resistance were observed in non‐seroconverters compared to seroconverters., INTRODUCTION In 2011, the HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) is highly effective for preventing sexual transmission of HIV [1]. Early [...]

Introduction: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included 'universal testing and treatment' on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. Methods: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. Results: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. Conclusions: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this arge cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided usefu data on the frequency of errors and provided more accurate data for HIV incidence estimates. Keywords: HIV incidence; seroconverters; HIV testing; community-randomized; Zambia; South Africa, (1) | INTRODUCTION Universal testing and treatment (UTT) for HIV prevention is an important component of HIV prevention programmes [1,2]. The HIV Prevention Trials Network (HPTN) 071 (PopART) trial, the [...]

Introduction: Across sub-Saharan Africa, selling sex puts young women at high risk of HIV. Some young women who sell sex (YWSS) may self-identify as sex workers, while others may not, having implications for how to reach them with HIV prevention. We describe characteristics, sexual behaviours and health service use of YWSS in Zimbabwe, comparing women who identified as female sex workers (FSW) and women who did not (non-identifying-YWSS), and explore factors associated with HIV infection. Methods: We analysed data from respondent-driven sampling (RDS) surveys among YWSS aged 18 to 24 implemented in six sites in Zimbabwe from April to July 2017. RDS was used to enrol YWSS into an impact evaluation of the multi-country DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored and Safe) Partnership, which provides comprehensive HIV prevention programming to adolescent girls and young women. Women completed an interviewer-administered questionnaire and were offered HIV testing services. We used logistic regression (RDS-II-weighted, normalized by site) to identify factors associated with prevalent HIV infection. Results: Forty-four seeds recruited 2387 YWSS. RDS-adjusted HIV prevalence was 24%; 67% of women identified as FSW. FSW were older and had lower educational attainment than non-identifying-YWSS. While 40% of FSW reported 10+ clients in the previous month, 9% of non-identifying-YWSS did so. FSW were more likely to have accessed HIV-related services, including HIV testing in the last six months (FSW: 70%; non-identifying-YWSS: 60%). Over half of all YWSS described selling sex as their main financial support (FSW: 88%; non-identifying YWSS: 54%). Increasing age, lower educational attainment, younger age of first selling sex and higher number of clients in the previous month were associated with prevalent HIV. Conclusions: YWSS in Zimbabwe have a high prevalence of HIV, reported high numbers of sexual partners and depend financially on selling sex. Non-identifying-YWSS differed socio-demographically to FSW, yet factors associated with HIV risk were similar for all women. Women not identifying as FSW were less likely to access services, suggesting they should be prioritized for HIV prevention. Network-based recruitment may enhance their inclusion in programmes, like DREAMS, which aim to reach young women at highest-risk with comprehensive health, HIV prevention and social protection services. Keywords: female sex worker; adolescents and young women; HIV infection; HIV prevention; Zimbabwe; Sub-Saharan Africa, 1 | INTRODUCTION In sub-Saharan Africa, adolescent girls and young women aged 15 to 24 are more vulnerable to HIV infection than their male peers and older women [1]. At [...]

Introduction: The HPTN071 (PopART) for Youth (P-ART-Y) study evaluated the acceptability and uptake of a community-level combination HIV prevention package including universal testing and treatment (UTT) among young people in Zambia and South Africa. We determined whether a four-question primary care level screening tool, validated for use in clinical settings, could enhance community (door-to-door) identification of undiagnosed HIV-positive younger adolescents (aged 10–14) who are frequently left out of HIV interventions. Method: Community HIV-care Providers (CHiPs) contacted and consented adolescents in their homes and offered them participation in the PopART intervention. CHiPs used a four question-screening tool, which included: history of hospital admission; recurring skin problems; poor health in last 3 months; and death of at least one parent. A "yes" response to one or more questions was classified as being "at risk" of being HIV-positive. Rapid HIV tests were offered to all children. Data were captured through an electronic data capture device from August 2016 to December 2017. The sensitivity, specificity, positive predictive value and negative predictive value were estimated for the screening tool, using the rapid HIV test result as the gold standard. Results: In our 14 study sites, 33,710 adolescents aged 10–14 in Zambia and 8,610 in South Africa participated in the study. About 1.3% (427/33,710) and 1.2% (106/8,610) self-reported to be HIV positive. Excluding the self-reported HIV-positive, we classified 11.3% (3,746/33,283) of adolescents in Zambia and 17.5% (1,491/8,504) in South Africa as "at risk". In Zambia the estimated sensitivity was 35.3% (95% CI 27.3%-44.2%) and estimated specificity was 88.9% (88.5%-89.2%). In South Africa the sensitivity was 72.3% (26.8%-94.9%) and specificity was 82.5% (81.6–83.4%). Conclusion: The sensitivity of the screening tool in a community setting in Zambia was low, so this tool should not be considered a substitute for universal testing where that is possible. In South Africa the sensitivity was higher, but with a wide confidence interval. Where universal testing is not possible the tool may help direct resources to adolescents more likely to be living with undiagnosed HIV. Trial registration: Clinical Trial Number:NCT01900977. [ABSTRACT FROM AUTHOR]

Background Through a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women's heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings. Methods and findings We directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years). In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period. Conclusions Substantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women., Author(s): Isolde Birdthistle 1,*, Daniel Kwaro 2, Maryam Shahmanesh 3,4, Kathy Baisley 1,3, Sammy Khagayi 2, Natsayi Chimbindi 3, Vivienne Kamire 2, Nondumiso Mthiyane 3, Annabelle Gourlay 1, Jaco Dreyer [...]