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Background HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. Methods and findings HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value [less than or equal to]0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. Conclusions In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. Trial registration ClinicalTrials.gov: NCT01900977., Author(s): L. Telisinghe 1,2,*, S. Floyd 3, D. MacLeod 3, A. Schaap 2,3, R. Dunbar 4, J. Bwalya 2, N. Bell-Mandla 4, E. Piwowar-Manning 5, D. Donnell 6, K. Shaunaube [...]

Background: Identifying successful strategies to improve participant retention in longitudinal studies remains a challenge. In this study we evaluated whether non-traditional fieldworker shifts (after hours during the week and weekends) enhanced participant retention when compared to retention during traditional weekday shifts in the HPTN 071 (PopART) population cohort (PC).Methods: HPTN 071 (PopART) PC participants were recruited and followed up in their homes on an annual basis by research fieldworkers over a 3-4 year period. The average number of successful follow-up visits, where a PC participant was found and retained in the study, was calculated for each of 3 visit schedules (early weekday shift, late weekday shift, and Saturday shift), and standardized to account for variation in fieldwork shift duration. We used one-way univariate analysis of variance (ANOVA) to describe differences in mean-successful visits and 95% confidence intervals between the shift types.Results: Data on 16 651 successful visits were included. Successful visit rates were higher when conducting Saturday visits (14.0; 95% CI: 11.3-16.6) compared to both regular (4.5; 95% CI: 3.7-5.3) and late weekday shifts (5.3; 95% CI: 4.7-5.8) overall and in all subgroup analyses (P<0.001). The successful visit rate was higher amongst women than men were during all shift types (3.2 vs. 1.3, p<0.001). Successful visit rates by shift type did not differ significantly by age, over time, by PC round or by community triplet.Conclusion: The number of people living with HIV continues to increase annually. High quality evidence from longitudinal studies remains critical for evaluating HIV prevention and treatment strategies. This study showed a significant benefit on participant retention through introduction of Saturday shifts for home visits and these data can make an important contribution to the emerging body of evidence for improving retention in longitudinal research.Trial Registration: PopART was approved by the Stellenbosch University Health Research Ethics Committees (N12/11/074), London School of Hygiene and Tropical Medicine (6326) ethics committee and the Division of AIDS (DAIDS) (Protocol ID 11865). PopART was registered with ClinicalTrials.gov (registration number NCT01900977 ). [ABSTRACT FROM AUTHOR]

This research study aims to examine the possibilities of Hyperledger Fabric (HLF) in the healthcare sector. The study addresses the gap in the knowledge base through developing customization techniques to enable the simplicity and efficacy of Electronic Medical Records (EMR) adoption for healthcare industry applications. The focus of this research explores methods of using blockchain technology that prioritise users. The investigation of several concepts used in developing web applications has been determined. The study identified that an open-source project, known as Hyperledger Fabric, can be utilised to construct a novel method of storing EMRs. The framework provides a test network that can be customised to satisfy the need of several projects, including storing medical records. This research additionally outlines the difficulties encountered and problems that need to be resolved before Hyperledger Fabric can be successfully implemented in healthcare systems. Considering all types of blockchains available, the needs are met by Hyperledger Fabric, which offers a distributed and secure environment for healthcare systems. Blockchain has the potential to transform healthcare by putting the patient at the centre of the system and enhancing health data protection and interoperability. Also, by using grant and revoke access mechanisms, patients have complete control over their medical information as well as authorized doctors who are allowed to view records. This functionality is made possible by the chaincode defined in the blockchain platform. The research study has both practitioner and research implications for the development of secure blockchain-based EMRs.

Background: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent.Methods: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months.Results: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B.Conclusions: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.). [ABSTRACT FROM AUTHOR]

Background: HIV treatment has clear Health-Related Quality-of-Life (HRQoL) benefits. However, little is known about how Universal Testing and Treatment (UTT) for HIV affects HRQoL. This study aimed to examine the effect of a combination prevention intervention, including UTT, on HRQoL among People Living with HIV (PLHIV)., Methods: Data were from HPTN 071 (PopART), a three-arm cluster randomised controlled trial in 21 communities in Zambia and South Africa (2013-2018). Arm A received the full UTT intervention of door-to-door HIV testing plus access to antiretroviral therapy (ART) regardless of CD4 count, Arm B received the intervention but followed national treatment guidelines (universal ART from 2016), and Arm C received standard care. The intervention effect was measured in a cohort of randomly selected adults, over 36 months. HRQoL scores, and the prevalence of problems in five HRQoL dimensions (mobility, self-care, performing daily activities, pain/discomfort, anxiety/depression) were assessed among all participants using the EuroQol-5-dimensions-5-levels questionnaire (EQ-5D-5L). We compared HRQoL among PLHIV with laboratory confirmed HIV status between arms, using adjusted two-stage cluster-level analyses., Results: At baseline, 7,856 PLHIV provided HRQoL data. At 36 months, the mean HRQoL score was 0.892 (95% confidence interval: 0.887-0.898) in Arm A, 0.886 (0.877-0.894) in Arm B and 0.888 (0.884-0.892) in Arm C. There was no evidence of a difference in HRQoL scores between arms (A vs C, adjusted mean difference: 0.003, -0.001-0.006; B vs C: -0.004, -0.014-0.005). The prevalence of problems with pain/discomfort was lower in Arm A than C (adjusted prevalence ratio: 0.37, 0.14-0.97). There was no evidence of differences for other HRQoL dimensions., Conclusions: The intervention did not change overall HRQoL, suggesting that raising HRQoL among PLHIV might require more than improved testing and treatment. However, PLHIV had fewer problems with pain/discomfort under the full intervention; this benefit of UTT should be maximised during roll-out., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KH received professional fees for advisory activities for Pfizer and GlaxoSmithKline for research unrelated to this study, and professional fees from the World Health Organization for research unrelated to this study. SG declares holding shares in AstraZeneca and GlaxoSmithKline.All other authors declare no competing interests., (© 2023 The Authors.)

Introduction: In 2021, there were 38.4 million people living with HIV (PLHIV) globally, of which 20.6 million (54%) were living in Eastern and Southern Africa. Longitudinal studies, inclusive of community randomized trials (CRTs), provide critical evidence to guide a broad range of health care interventions including HIV prevention. In this study, we have used an individual-level cohort study design to evaluate the association between sex and other baseline characteristics and participant retention in the HPTN 071 (PopART) trial in Zambia and South Africa., Methods: HPTN 071 (PopART) was a community randomized trial (CRT) conducted from 2013 to 2018, in 21 communities. The primary outcome was measured in a randomly selected population cohort (PC), followed up over 3 to 4 years at annual rounds. PC retention was defined as completion of an annual follow-up questionnaire. Baseline characteristics were described by study arm and Poisson regression analyses used to measure the association between baseline factors and retention. In addition, we present a description of researcher-documented reasons for study withdrawal by PC participants., Results: Of the 38,474 participants enrolled during the first round of the trial (PC0), most were women (27,139, 71%) and 73% completed at least one follow-up visit. Retention was lower in men (adj RR: 0.90; 95% CI: 0.88, 0.91) and higher among older participants (adj RR: 1.23; 95% CI 1.20, 1.26) when comparing ages 35-44 to 18-24 years. Retention was higher among individuals with high socioeconomic status (SES) (adj RR 1.16; 95% CI 1.14, 1.19) and medium SES (adj RR 1.12; 95% CI 1.09, 1.14) compared to low SES. The most common reasons for study withdrawal were study refusal (23%) and relocation outside the CRT catchment area (66%)., Conclusion: Despite challenges, satisfactory retention outcomes were achieved in PopART with limited variability across study arms. In keeping with other studies, younger age, male sex, and lower SES were associated with lower levels of retention. Relocation outside of catchment area was the most common reason for non-retention in this CRT., (© 2023. The Author(s).)

Objectives: Voluntary medical male circumcision (VMMC) is an important component of combination HIV prevention. Inclusion of traditionally circumcised HIV negative men in VMMC uptake campaigns may be important if traditional male circumcision is less protective against HIV acquisition than VMMC., Methods: We used data from the HIV Prevention Trials Network (HPTN) 071 (PopART) study. This cluster-randomized trial assessed the impact of a combination prevention package on population-level HIV incidence in 21 study communities in Zambia and South Africa. We evaluated uptake of VMMC, using a two-stage analysis approach and used discrete-time survival analysis to evaluate the association between the types of male circumcision and HIV incidence., Results: A total of 10 803 HIV-negative men with self-reported circumcision status were included in this study. At baseline, 56% reported being uncircumcised, 26% traditionally circumcised and 18% were medically circumcised. During the PopART intervention, 11% of uncircumcised men reported uptake of medical male circumcision. We found no significant difference in the uptake of VMMC in communities receiving the PopART intervention package and standard of care {adj. rate ratio=1·10 [95% confidence interval (CI) 0.82, 1.50, P  = 0.48]}. The rate of HIV acquisition for medically circumcised men was 70% lower than for those who were uncircumcised adjusted hazard ratio (adjHR) = 0.30 (95% CI 0.16-0.55; P  < 0.0001). There was no difference in rate of HIV acquisition for traditionally circumcised men compared to those uncircumcised adjHR = 0.84 (95% CI 0.54, 1.31; P  = 0.45)., Conclusions: Household-based delivery of HIV testing followed by referral for medical male circumcision did not result in substantial VMMC uptake. Traditional circumcision is not associated with lower risk of HIV acquisition., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multi-assay algorithms (MAAs) are used to estimate population-level HIV incidence and identify individuals with recent infection. Many MAAs use low viral load (VL) as a biomarker for long-term infection. This could impact incidence estimates in settings with high rates of early HIV treatment initiation. We evaluated the performance of two MAAs that do not include VL., Methods: Samples were collected from 219 seroconverters (infected < 1 year) and 4376 non-seroconverters (infected > 1 year) in the HPTN 071 (PopART) trial; 28.8% of seroconverter samples and 73.2% of non-seroconverter samples had VLs ≤ 400 copies/mL. Samples were tested with the Limiting Antigen Avidity assay (LAg) and JHU BioRad-Avidity assays. Antibody reactivity to two HIV peptides was measured using the MSD U-PLEX assay. Two MAAs were evaluated that do not include VL: a MAA that includes the LAg-Avidity assay and BioRad-Avidity assay (LAg + BR) and a MAA that includes the LAg-Avidity assay and two peptide biomarkers (LAg + PepPair). Performance of these MAAs was compared to a widely used MAA that includes LAg and VL (LAg + VL)., Results: The incidence estimate for LAg + VL (1.29%, 95% CI: 0.97-1.62) was close to the observed longitudinal incidence (1.34% 95% CI: 1.17-1.53). The incidence estimates for the other two MAAs were higher (LAg + BR: 2.56%, 95% CI 2.01-3.11; LAg + PepPair: 2.84%, 95% CI: 1.36-4.32). LAg + BR and LAg + PepPair also misclassified more individuals infected > 2 years as recently infected than LAg + VL (1.2% [42/3483 and 1.5% [51/3483], respectively, vs. 0.2% [6/3483]). LAg + BR classified more seroconverters as recently infected than LAg + VL or LAg + PepPair (80 vs. 58 and 50, respectively) and identified ~ 25% of virally suppressed seroconverters as recently infected., Conclusions: The LAg + VL MAA produced a cross-sectional incidence estimate that was closer to the longitudinal estimate than two MAAs that did not include VL. The LAg + BR MAA classified the greatest number of individual seroconverters as recently infected but had a higher false recent rate., (© 2022. The Author(s).)

Background: Comprehensive HIV prevention strategies have raised concerns that knowledge of interventions to reduce risk of HIV infection might mitigate an individual's perception of risk, resulting in riskier sexual behaviour. We investigated the prespecified secondary outcomes of the HPTN 071 (PopART) trial to determine whether a combination HIV prevention strategy, including universal HIV testing and treatment, changed sexual behaviour; specifically, we investigated whether there was evidence of sexual risk compensation., Methods: HPTN 071 (PopART) was a cluster-randomised trial conducted during 2013-18, in which we randomly assigned 21 communities with high HIV prevalence in Zambia and South Africa (total population, approximately 1 million) to combination prevention intervention with universal antiretroviral therapy (ART; arm A), prevention intervention with ART provided according to local guidelines (universal since 2016; arm B), or standard of care (arm C). The trial included a population cohort of approximately 2000 randomly selected adults (aged 18-44 years) in each community (N=38 474 at baseline) who were followed up for 36 months. A prespecified secondary objective was to evaluate the impact of the PopART intervention compared with standard of care on herpes simplex virus type 2 (HSV-2) and sexual behaviour (N=20 422 completed final visit). Secondary endpoints included differences in sexual risk behaviour measures at 36 months and were assessed using a two-stage method for matched cluster-randomised trials. This trial is registered with ClinicalTrials. gov, number NCT01900977., Findings: The PopART intervention did not substantially change probability of self-reported multiple sex partners, sexual debut, or pregnancy in women at 36 months. Adjusted for baseline community prevalence, reported condomless sex was significantly lower in arm A versus arm C (adjusted prevalence ratio 0·80 [95% CI 0·64-0·99]; p=0·04) but not in arm B versus arm C (0·94 [0·76-1·17]; p=0·55). 3-year HSV-2 incidence was reduced in arm B versus arm C (adjusted risk ratio 0·76 [95% CI 0·63-0·92]; p=0·010); no significant change was shown between arm A versus arm C (0·89 [0·73-1·08]; p=0·199)., Interpretation: We found little evidence of any change in sexual behaviour owing to the PopART interventions, and reassuringly for public health, we saw no evidence of sexual risk compensation. The findings do not help to explain the differences between the two intervention groups of the HPTN 071 (PopART) trial., Funding: National Institute of Allergy and Infectious Diseases, the National Institutes of Health, the International Initiative for Impact Evaluation (3ie), the Bill & Melinda Gates Foundation, the US President's Emergency Plan for AIDS Relief, and the Medical Research Council UK., Competing Interests: Declaration of interests HA and DD report on behalf of the entire study team, grant funding from: the NIH, the international initiative for impact evaluation (3ie), the US President's Emergency Plan for AIDS Relief (PEPFAR), and the Bill & Melinda Gates Foundation (also reflected in Acknowledgments). HA reports membership in the technical review panel for the Global Fund. NB-M is a member on the HPTN Ethics Working Group. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: In 2014, UNAIDS set the target that 90% of individuals on antiretroviral therapy (ART) be virally suppressed. Here, we use data from the HPTN 071 (PopART) trial to report whether the introduction of universal testing and treatment has affected viral suppression or treatment adherence among individuals who self-reported they were taking ART, and identify risk factors for these outcomes., Methods: This was a cross-sectional study nested within the randomly selected population cohort of the PopART trial. The trial took place in 21 communities in Zambia and South Africa. Analyses included 3570 HIV-positive participants who were seen at the second follow-up visit in 2016-17 and who self-reported that they were currently taking ART. Viral suppression was defined as HIV RNA of less than 400 copies per mL from a blood sample collected during the cohort visit, and ART adherence was measured using self-reporting (reported as no missed pills in last 7 days). Prevalences of these outcomes were compared across three trial arms using a two-stage approach suitable for clustered data. Each arm consisted of seven communities, with one arm receiving a combination HIV prevention package including immediate ART initiation, one receiving a combination HIV prevention package excluding immediate ART initiation and one arm receving standard of care. Risk factors for each of the outcomes were assessed using logistic regression., Findings: Among the 3570 participants who self-reported that they were currently on ART, 416 (11·7%) of 3554 were not virally suppressed (16 were missing viral suppression status) and 345 (9·7%) of 3566 reported being non-adherent to ART (four were missing adherence status). The proportion not virally suppressed was higher in communities in South Africa (195 [16·4%] of 1191) than in Zambia (221 [9·4%] of 2363). There was no evidence that the prevalence of the outcomes differed between trial arms. There was evidence that men, younger individuals, individuals who reported participating in harmful alcohol use, and those who reported internalised stigma were more likely to be non-adherent, and not virally suppressed., Interpretation: The results assuaged concerns that early ART initiation in a universal testing and treatment setting could lead to reduced adherence and viral suppression., Funding: US National Institute of Allergy and Infectious Diseases (which is a part of the National Institutes of Health), the International Initiative for Impact Evaluation with support from the Bill & Melinda Gates Foundation, US President's Emergency Plan for AIDS Relief, and Medical Research Council UK., Competing Interests: Declaration of interests AM, EP-M, and SHE report funding from the National Institutes of Health (NIH). DD and TS reports funding from the National Institute of Allergy and Infectious Diseases (NIAID) and NIH. DM, SFl, and HA report funding from NIH, the US President's Emergency Plan for AIDS Relief (PEPFAR), the Bill & Melinda Gates Foundation, and the International Initiative for Impact Evaluation. SFid reports participation on a Data and Safety Monitoring Board for the Disasters Emergency Committee HIV vaccine trial. GH reports funding from NIH, NIAID, and the National Institute of Mental Health, the Gates Foundation, South African TB Think Tank, the United States Agency for International Development, Unitaid, Stop TB partnership, and participation on an advisory board for Templeton World Charity Foundation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments., Methods: Samples were obtained from 220 seroconverters (infected <1 year) and 4,396 non-seroconverters (infected >1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads ≤400 copies/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay., Results: The MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections >2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression., Conclusions: The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: None of the authors has a conflict of interest or potential conflict of interest, with the following exceptions: Susan Eshleman has collaborated on research studies with investigators from Abbott Diagnostics; Abbott Diagnostics provided reagents for previous research studies.

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 <2.8 ODn + BioRad Avidity Index <95% + VL >400 copies/ml; LAg+VL MAA: LAg-Avidity <1.5 ODn + VL >1000 copies/ml; Rapid+VL MAA: Asanté 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 (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17-1.53). Estimates of incidence were similar to observed incidence for MAA-C, 1.26% (95% CI: 1.02-1.51) and the LAg+VL MAA, 1.29 (95% CI: 0.97-1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69-1.15, p<0.01)., 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., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: The HPTN 071 (PopART) trial showed that a combination HIV prevention package including universal HIV testing and treatment (UTT) reduced population-level incidence of HIV compared with standard care. However, evidence is scarce on the costs and cost-effectiveness of such an intervention., Methods: Using an individual-based model, we simulated the PopART intervention and standard care with antiretroviral therapy (ART) provided according to national guidelines for the 21 trial communities in Zambia and South Africa (for all individuals aged >14 years), with model parameters and primary cost data collected during the PopART trial and from published sources. Two intervention scenarios were modelled: annual rounds of PopART from 2014 to 2030 (PopART 2014-30; as the UNAIDS Fast-Track target year) and three rounds of PopART throughout the trial intervention period (PopART 2014-17). For each country, we calculated incremental cost-effectiveness ratios (ICERs) as the cost per disability-adjusted life-year (DALY) and cost per HIV infection averted. Cost-effectiveness acceptability curves were used to indicate the probability of PopART being cost-effective compared with standard care at different thresholds of cost per DALY averted. We also assessed budget impact by projecting undiscounted costs of the intervention compared with standard care up to 2030., Findings: During 2014-17, the mean cost per person per year of delivering home-based HIV counselling and testing, linkage to care, promotion of ART adherence, and voluntary medical male circumcision via community HIV care providers for the simulated population was US$6·53 (SD 0·29) in Zambia and US$7·93 (0·16) in South Africa. In the PopART 2014-30 scenario, median ICERs for PopART delivered annually until 2030 were $2111 (95% credible interval [CrI] 1827-2462) per HIV infection averted in Zambia and $3248 (2472-3963) per HIV infection averted in South Africa; and $593 (95% CrI 526-674) per DALY averted in Zambia and $645 (538-757) per DALY averted in South Africa. In the PopART 2014-17 scenario, PopART averted one infection at a cost of $1318 (1098-1591) in Zambia and $2236 (1601-2916) in South Africa, and averted one DALY at $258 (225-298) in Zambia and $326 (266-391) in South Africa, when outcomes were projected until 2030. The intervention had almost 100% probability of being cost-effective at thresholds greater than $700 per DALY averted in Zambia, and greater than $800 per DALY averted in South Africa, in the PopART 2014-30 scenario. Incremental programme costs for annual rounds until 2030 were $46·12 million (for a mean of 341 323 people) in Zambia and $30·24 million (for a mean of 165 852 people) in South Africa., Interpretation: Combination prevention with universal home-based testing can be delivered at low annual cost per person but accumulates to a considerable amount when scaled for a growing population. Combination prevention including UTT is cost-effective at thresholds greater than $800 per DALY averted and can be an efficient strategy to reduce HIV incidence in high-prevalence settings., Funding: US National Institutes of Health, President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess the impact of a combination HIV prevention intervention including universal testing and treatment (UTT) on HIV stigma among people living with HIV, and among community members and health workers not living with HIV., Design: This HIV stigma study was nested in the HPTN 071 (PopART) trial, a three-arm cluster randomised trial conducted between 2013 and 2018 in 21 urban/peri-urban communities (12 in Zambia and nine in South Africa)., Methods: Using an adjusted two-stage cluster-level analysis, controlling for baseline imbalances, we compared multiple domains of stigma between the trial arms at 36 months. Different domains of stigma were measured among three cohorts recruited across all study communities: 4178 randomly sampled adults aged 18-44 who were living with HIV, and 3487 randomly sampled adults and 1224 health workers who did not self-report living with HIV., Results: Prevalence of any stigma reported by people living with HIV at 36 months was 20.2% in arm A, 26.1% in arm B, and 19.1% in arm C (adjusted prevalence ratio, A vs. C 1.01 95% CI 0.49-2.08, B vs. C 1.34 95% CI 0.65-2.75). There were no significant differences between arms in any other measures of stigma across all three cohorts. All measures of stigma reduced over time (0.2--4.1% reduction between rounds) with most reductions statistically significant., Conclusion: We found little evidence that UTT either increased or decreased HIV stigma measured among people living with HIV, or among community members or health workers not living with HIV. Stigma reduced over time, but slowly. CLINICALTRIALS., Gov Number: NCT01900977.

Objectives: Adherence to antiretroviral therapy (ART) leads to viral suppression for people living with HIV (PLHIV) and is critical for both individual health and reducing onward HIV transmission. HIV stigma is a risk factor that can undermine adherence. We explored the association between HIV stigma and self-reported ART adherence among PLHIV in 21 communities in the HPTN 071 (PopART) trial in Zambia and the Western Cape of South Africa., Methods: We conducted a cross-sectional analysis of baseline data collected between 2013 and 2015, before the roll-out of trial interventions. Questionnaires were conducted, and consenting participants provided a blood sample for HIV testing. Poor adherence was defined as self-report of not currently taking ART, missing pills over the previous 7 days or stopping treatment in the previous 12 months. Stigma was categorised into three domains: community, health setting and internalised stigma. Multivariable logistic regression was used for analysis., Results: Among 2020 PLHIV self-reporting ever taking ART, 1888 (93%) were included in multivariable analysis. Poor ART adherence was reported by 15.8% (n = 320) of participants, and 25.7% (n = 519) reported experiencing community stigma, 21.5% (n = 434) internalised stigma, and 5.7% (n = 152) health setting stigma. PLHIV who self-reported previous experiences of community and internalised stigma more commonly reported poor ART adherence than those who did not (aOR 1.63, 95% CI 1.21 -2.19, P = 0.001 and aOR 1.31, 95% CI 0.96-1.79, P = 0.09)., Conclusions: HIV stigma was associated with poor ART adherence. Roll-out of universal treatment will see an increasingly high proportion of PLHIV initiated on ART. Addressing HIV stigma could make an important contribution to supporting lifelong ART adherence., (© 2020 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

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., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objective: To compare number of days lost to illness or accessing healthcare for HIV-positive and HIV-negative individuals working in the informal and formal sectors in South Africa and Zambia., Design: As part of the HPTN 071 (PopART) study, data on adults aged 18-44 years were gathered from cross-sectional surveys of random general population samples in 21 communities in Zambia and South Africa. Data on the number of productive days lost in the last 3 months, laboratory-confirmed HIV status, labour force status, age, ethnicity, education, and recreational drug use was collected., Methods: Differences in productive days lost between HIV-negative and HIV-positive individuals ('excess productive days lost') were estimated with negative binomial models, and results disaggregated for HIV-positive individuals after various durations on antiretroviral treatment (ART)., Results: From samples of 19 330 respondents in Zambia and 18 004 respondents in South Africa, HIV-positive individuals lost more productive days to illness than HIV-negative individuals in both countries. HIV-positive individuals in Zambia lost 0.74 excess productive days [95% confidence interval (CI) 0.48-1.01; P < 0.001] to illness over a 3-month period. HIV-positive in South Africa lost 0.13 excess days (95% CI 0.04-0.23; P = 0.007). In Zambia, those on ART for less than 1 year lost most days, and those not on ART lost fewest days. In South Africa, results disaggregated by treatment duration were not statistically significant., Conclusion: There is a loss of work and home productivity associated with HIV, but it is lower than existing estimates for HIV-positive formal sector workers. The findings support policy makers in building an accurate investment case for HIV interventions.

Background: Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels., Methods: The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence., Results: A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92; P < .001)., Conclusions: There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention.

Objective: To describe the prevalence and determinants of HIV stigma in 21 communities in Zambia and South Africa., Design: Analysis of baseline data from the HPTN 071 (PopART) cluster-randomized trial. HIV stigma data came from a random sample of 3859 people living with HIV. Community-level exposures reflecting HIV fears and judgements and perceptions of HIV stigma came from a random sample of community members not living with HIV (n = 5088), and from health workers (HW) (n = 851)., Methods: We calculated the prevalence of internalized stigma, and stigma experienced in the community or in a healthcare setting in the past year. We conducted risk-factor analyses using logistic regression, adjusting for clustering., Results: Internalized stigma (868/3859, prevalence 22.5%) was not associated with sociodemographic characteristics but was less common among those with a longer period since diagnosis (P = 0.043). Stigma experienced in the community (853/3859, 22.1%) was more common among women (P = 0.016), older (P = 0.011) and unmarried (P = 0.009) individuals, those who had disclosed to others (P < 0.001), and those with more lifetime sexual partners (P < 0.001). Stigma experienced in a healthcare setting (280/3859, 7.3%) was more common among women (P = 0.019) and those reporting more lifetime sexual partners (P = 0.001) and higher wealth (P = 0.003). Experienced stigma was more common in clusters wherever community members perceived higher levels of stigma, but was not associated with the beliefs of community members or HW., Conclusion: HIV stigma remains unacceptably high in South Africa and Zambia and may act as barrier to HIV prevention and treatment. Further research is needed to understand its determinants.

Introduction: Population-wide HIV testing services (HTS) must be delivered in order to achieve universal antiretroviral treatment (ART) coverage. To accurately deliver HTS at such scale, non-facility-based HIV point-of-care testing (HIV-POCT) is necessary but requires rigorous quality assurance (QA). This study assessed the performance of community-wide HTS in Zambia and South Africa (SA) as part of the HPTN 071 (PopART) study and explores the impact of quality improvement interventions on HTS performance., Methods: Between 2014 and 2016, HIV-POCT was undertaken within households both as part of the randomly selected HPTN 071 research cohort (Population Cohort [PC]) and as part of the intervention provided by community HIV-care providers. HIV-POCT followed national algorithms in both countries. Consenting PC participants provided a venous blood sample in addition to being offered HIV-POCT. We compared results obtained in the PC using a laboratory-based gold standard (GS) testing algorithm and HIV-POCT. Comprehensive QA mechanisms were put in place to support the community-wide testing. Participants who were identified as having a false negative or false positive HIV rapid test were revisited and offered retesting., Results: We initially observed poor sensitivity (45-54%, 95% confidence interval [CI] 31-69) of HIV-POCT in the PC in SA compared to sensitivity in Zambia for the same time period of 95.8% (95% CI 93-98). In both countries, specificity of HIV-POCT was >98%. With enhanced QA interventions and adoption of the same HIV-POCT algorithm, sensitivity in SA improved to a similar level as in Zambia., Conclusions: This is one of the first reports of HIV-POCT performance during wide-scale delivery of HTS compared to a GS laboratory algorithm. HIV-POCT in a real-world setting had a lower sensitivity than anticipated. Appropriate choice of HIV-POCT algorithms, intensive training and supervision, and robust QA mechanisms are necessary to optimize HIV-POCT test performance when testing is delivered at a community level. HIV-POCT in clients who did not disclose that they were on ART may have contributed to false negative HIV-POCT results and should be the topic of future research., Competing Interests: No authors declare a conflict of interests.