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: Introduction: HIV controllers have low viral loads (VL) without antiretroviral treatment (ART). We evaluated viraemic control in a community‐randomized trial conducted in Zambia and South Africa that evaluated the impact of a combination prevention intervention on HIV incidence (HPTN 071 [PopART]; 2013–2018). Methods: VL and antiretroviral (ARV) drug testing were performed using plasma samples collected 2 years after enrolment for 4072 participants who were HIV positive at the start of the study intervention. ARV drug use was assessed using a qualitative laboratory assay that detects 22 ARV drugs in five drug classes. Participants were classified as non‐controllers if they had a VL ≥2000 copies/ml with no ARV drugs detected at this visit. Additional VL and ARV drug testing was performed at a second annual study visit to confirm controller status. Participants were classified as controllers if they had VLs Results: The final cohort included 126 viraemic controllers and 766 non‐controllers who had no ARV drugs detected. The prevalence of controllers among the 4072 persons assessed was 3.1% (95% confidence interval [CI]: 2.6%, 3.6%). This should be considered a minimum estimate, since high rates of ARV drug use in the parent study limited the ability to identify controllers. Among the 892 participants in the final cohort, controller status was associated with biological sex (female > male, p = 0.027). There was no significant association between controller status and age, study country or herpes simplex virus type 2 (HSV‐2) status at study enrolment. Conclusions: To our knowledge, this report presents the first large‐scale, population‐level study evaluating the prevalence of viraemic control and associated factors in Africa. A key advantage of this study was that a biomedical assessment was used to assess ARV drug use (vs. self‐reported data). This study identified a large cohort of HIV controllers and non‐controllers not taking ARV drugs, providing a unique repository of longitudinal samples for additional research. This cohort may be useful for further studies investigating the mechanisms of virologic control., INTRODUCTION HIV controllers naturally suppress their HIV viral load (VL) to low levels without antiretroviral treatment (ART) [1]. Elite controllers maintain VLs Previous population‐level studies have reported the prevalence of [...]

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, [...]

Background: High HIV viral loads (VL) are associated with increased morbidity, mortality, and on-going transmission. HIV controllers maintain low VLs in the absence of antiretroviral therapy (ART). We previously used a massively multiplexed antibody profiling assay (VirScan) to compare antibody profiles in HIV controllers and persons living with HIV (PWH) who were virally suppressed on ART. In this report, we used VirScan to evaluate whether antibody reactivity to specific HIV targets and broad reactivity across the HIV genome was associated with VL and controller status 1–2 years after infection. Methods: Samples were obtained from participants who acquired HIV infection in a community-randomized trial in Africa that evaluated an integrated strategy for HIV prevention (HPTN 071 PopART). Controller status was determined using VL and antiretroviral (ARV) drug data obtained at the seroconversion visit and 1 year later. Viremic controllers had VLs <2,000 copies/mL at both visits; non-controllers had VLs >2,000 copies/mL at both visits. Both groups had no ARV drugs detected at either visit. VirScan testing was performed at the second HIV-positive visit (1–2 years after HIV infection). Results: The study cohort included 13 viremic controllers and 64 non-controllers. We identified ten clusters of homologous peptides that had high levels of antibody reactivity (three in gag, three in env, two in integrase, one in protease, and one in vpu). Reactivity to 43 peptides (eight unique epitopes) in six of these clusters was associated with lower VL; reactivity to six of the eight epitopes was associated with HIV controller status. Higher aggregate antibody reactivity across the eight epitopes (more epitopes targeted, higher mean reactivity across all epitopes) and across the HIV genome was also associated with lower VL and controller status. Conclusions: We identified HIV antibody targets associated with lower VL and HIV controller status 1–2 years after infection. Robust aggregate responses to these targets and broad antibody reactivity across the HIV genome were also associated with lower VL and controller status. These findings provide novel insights into the relationship between humoral immunity and viral containment that could help inform the design of antibody-based approaches for reducing HIV VL. [ABSTRACT FROM AUTHOR]

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 [...]

Introduction: Cross-sectional incidence testing is used to estimate population-level HIV incidence and measure the impact of prevention interventions. There are limited data evaluating the accuracy of estimates in settings where antiretroviral therapy coverage and levels of viral suppression are high. Understanding cross-sectional incidence estimates in these settings is important as viral suppression can lead to false recent test results. We compared the accuracy of multi-assay algorithms (MAA) for incidence estimation to that observed in the community-randomized HPTN 071 (PopART) trial, where the majority of participants with HIV infection were virally suppressed. Methods: HIV incidence was assessed during the second year of the study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016-2017). Incidence estimates from three MAAs were compared to the observed incidence between years 1 and 2 (MAA-C: LAg-Avidity 400 copies/ml; LAg+VL MAA: LAg-Avidity 1000 copies/ml; Rapid+VL MAA: Asante recent rapid result + VL >1000 copies/ml). The mean duration of recent infection (MDRI) used for the three MAAs was 248, 130 and 180 days, respectively. Results and discussion: The study consisted of: 15,845 HIV-negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV-positive participants at the 2-year visit. Sixty four (29%) of the seroconverters and 3227 (72%) prevelant positive participants were virally supressed ( Conclusions: MAA-C and the LAg+VL MAA provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting that the MDRI recommended by the manufacturer is too long or the assay is not accurately detecting enough recent infections. Keywords: validation study; cross-sectional incidence estimation; sub-Saharan Africa; HPTN; PopART; multi-assay algorithm, 1 | INTRODUCTION HIV incidence is the rate of new HIV infections in a population and the primary measure in evaluating the state of the epidemic and the effectiveness of [...]

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 [...]

Introduction: Achieving 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. Discussion: These 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 inkage 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 universa 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. Conclusions: These 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 eve 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. Keywords: HIV testing; antiretroviral therapy; HIV elimination; HIV care continuum; HIV prevention; HIV care continuum; public health; universal access, (1) | INTRODUCTION HIV 'treatment as prevention' captivated the HIV field over a decade ago. When antiretroviral therapy (ART) was shown to be associated with the secondary benefit of HIV [...]

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: Integrating standardized measures of HIV stigma and discrimination into research studies of emerging HIV prevention approaches could enhance uptake and retention of these approaches, and care and treatment for people living with HIV (PLHIV), by informing stigma mitigation strategies. We sought to develop a succinct set of measures to capture key domains of stigma for use in research on HIV prevention technologies. Methods: From 2013 to 2015, we collected baseline data on HIV stigma from three populations (PLHIV (N = 4053), community members (N = 5782) and health workers (N = 1560)) in 21 study communities in South Africa and Zambia participating in the HPTN 071 (PopART) cluster-randomized trial. Forty questions were adapted from a harmonized set of measures developed in a consultative, global process. Informed by theory and factor analysis, we developed seven scales, with values ranging from 0 to 3, based on a 4-point agreement Likert, and calculated means to assess different aspects of stigma. Higher means reflected more stigma. We developed two measures capturing percentages of PLHIV who reported experiencing any stigma in communities or healthcare settings in the past 12 months. We validated our measures by examining reliability using Cronbach's alpha and comparing the distribution of responses across characteristics previously associated with HIV stigma. Results: Thirty-five questions ultimately contributed to seven scales and two experience measures. All scales demonstrated acceptable to very good internal consistency. Among PLHIV, a scale captured internalized stigma, and experience measures demonstrated that 22.0% of PLHIV experienced stigma in the community and 7.1% in healthcare settings. Three scales for community members assessed fear and judgement, perceived stigma in the community and perceived stigma in healthcare settings. Similarly, health worker scales assessed fear and judgement, perceived stigma in the community and perceived co-worker stigma in healthcare settings. A higher proportion of community members and health workers reported perceived stigma than the proportion of PLHIV who reported experiences of stigma. Conclusions: We developed novel, valid measures that allowed for triangulation of HIV stigma across three populations in a large-scale study. Such comparisons will illuminate how stigma influences and is influenced by programmatic changes to HIV service delivery over time. Keywords: HIV; stigma; discrimination; measurement; Sub-Saharan Africa; antiretroviral therapy, 1 | INTRODUCTION A number of efficacious technologies are now available to prevent HIV transmission [1-3], however, their population impact will depend upon the public's capacity to take up and [...]

: 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 [...]

Background Although Zambia has integrated HIV-self-testing (HIVST) into its Human Immunodefciency Virus (HIV) regulatory frameworks, few best practices to optimize the use of HIV self-testing to increase testing coverage have been documented. We conducted a prospective case study to understand contextual factors guiding implementation of four HIVST distribution models to inform scale-up in Zambia. Methods We used the qualitative case study method to explore user and provider experiences with four HIVST distribution models (two secondary distribution models in Antenatal Care (ANC) and Antiretroviral Therapy (ART) clinics, community-led, and workplace) to understand factors infuencing HIVST distribution. Participants were purposefully selected based on their participation in HIVST and on their ability to provide rich contextual experience of the distribution models. Data were collected using observations (n=31), group discussions (n=10), and in-depth interviews (n=77). Data were analyzed using the thematic approach and aligned to the four Consolidated Framework for Implementation Research (CFIR) domains. Results Implementation of the four distribution models was infuenced by an interplay of outer and inner setting factors. Inadequate compensation and incentives for distributors may have contributed to distributor attrition in the community-led and workplace HIVST models. Stockouts, experienced at the start of implementation in the secondary-distribution and community-led distribution models often disrupted distribution. The existence of policy and practices aided integration of HIVST in the workplace. External factors complimented internal factors for successful implementation. For instance, despite distributor attrition leading to excessive workload, distributors often multi-tasked to keep up with demand for kits, even though distribution points were geographically widespread in the workplace, and to a less extent in the community-led models. Use of existing communication platforms such as lunchtime and safety meetings to promote and distribute kits, peers to support distributors, reduction in trips by distributors to replenish stocks, increase in monetary incentives and reorganisation of stakeholder roles proved to be good adaptations. Conclusion HIVST distribution was infuenced by a combination of contextual factors in variable ways. Understanding how the factors interacted in real world settings informed adaptations to implementation devised to minimize disruptions to distribution. [ABSTRACT FROM AUTHOR]

Introduction: The use of antigen rapid tests (Ag-RDTs) for self-testing is an important element of the COVID-19 control strategy and has been widely supported. However, scale-up of self-testing for COVID-19 in sub-Saharan Africa is still insufficient and there is limited evidence on the acceptability of self-testing and agreement between Ag-RDT self-testing and Ag-RDT testing by professional users. A joint collaboration (Botnar Research Centre for Child Health-European & Developing countries Clinical Trials Partnership)was established between Lesotho and Zambia to address these gaps in relation to Ag-RDT self-testing and contribute to increasing its use in the region. Methods: A cross-sectional study was conducted with qualitative and quantitative data analysis. Firstly, 14 in-depth cognitive interviews (5 in Zambia and 9 in Lesotho) were performed to assess the participants' understanding of the instructions for use (IFU) for self-testing. In a second step, evaluation of test agreement between Ag-RDT self-testing and Ag-RDT testing by professional user using SD Biosensor STANDARD Q COVID-19 Ag-RDT was performed. In Zambia, usability and acceptability of self-testing were also assessed. Results: Cognitive interviews in Lesotho and Zambia showed overall good understanding of IFU. In Zambia, acceptability of self-testing was high, though some participants had difficulties in conducting certain steps in the IFU correctly. Agreement between Ag-RDT self-test and Ag-RDT by professional users in Lesotho (428 participants) and Zambia (1136 participants) was high, 97.3% (403/414, 95% CI: 95.3–98.7) and 99.8% (1116/1118, 95% CI: 99.4–100) respectively. Conclusion: Findings from this study support the use of Ag-RDT self-testing within COVID-19 control strategies in sub-Saharan Africa, contributing to increase the testing capacity and access in hard-to reach settings. [ABSTRACT FROM AUTHOR]

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]