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BACKGROUND:HPTN071(PopART) is a 3-arm community-randomised study in 21 peri-urban/urban communities in Zambia and the Western Cape of South Africa, with high HIV prevalence and high mobility especially among young adults. In Arm A communities, from November 2013 community HIV care providers (CHiPs) have delivered the "PopART" universal-test-and-treat (UTT) package in annual rounds, during which they visit all households and offer HIV testing. CHiPs refer HIV-positive (HIV+) individuals to routine HIV clinic services, where universal ART (irrespective of CD4 count) is offered, with re-visits to support linkage to care. The overall goal is to reduce population-level adult HIV incidence, through achieving high HIV testing and treatment coverage. METHODS AND FINDINGS:The second annual round was June 2015-October 2016. Included in analysis are all individuals aged ≥15 years who consented to participate, with extrapolation to the total population. Our three main outcomes are (1) knowledge of HIV+ status (2) ART coverage, by the end of Round 2 (R2) and compared with the start of R2, and (3) retention on ART on the day of consenting to participate in R2. We used "time-to-event" methods to estimate the median time to start ART after referral to care. CHiPs visited 45,631 households during R2, ~98% of the estimated total across the four communities, and for 94% (43,022/45,631) consent was given for all household members to be listed on the CHiPs' electronic register; 120,272 individuals aged ≥15 years were listed, among whom 64% of men (37,265/57,901) and 86% (53,516/62,371) of women consented to participate in R2. We estimated there were 6,521 HIV+ men and 10,690 HIV+ women in the total population of visited households; and that ~80% and ~90% of HIV+ men and women respectively knew their HIV+ status by the end of R2, fairly similar across age groups but lower among those who did not participate in Round 1 (R1). Among those who knew their HIV+ status, ~80% of both men and women were on ART by the end of R2, close to 90% among men aged ≥45 and women aged ≥35 years, but lower among younger adults, those who were resident in R1 but did not participate in R1, and those who were newly resident in the area of the community in which they were living in R2. Overall ART coverage was ~65% among HIV+ men and ~75% among HIV+ women, compared with the cumulative 90-90 target of 81%. Among those who reported ever taking ART, 93% of men and 95% of women self-reported they were on ART and missed 0 pills in the last 3 days. The median time to start ART after referral to care was ~6 months in R2, similar across the age range 25-54 years, compared with ~9.5 months in R1. The two main limitations to our findings were that a comparison with control-arm communities cannot be made until the end of the study; and that to extrapolate to the total population, assumptions were required about individuals who were resident, but did not participate, in R2. CONCLUSIONS:Overall coverage against the 90-90 targets was high after two years of intervention, but was lower among men, individuals aged 18-34 years, and those who did not participate in R1. Our findings reflect the relative difficulties for CHiPs to contact men at home, compared with women, and that it is challenging to reach high levels of testing and treatment coverage in communities with substantial mobility and in-migration. The shortened time to start ART after referral to care in R2, compared with R1, was likely attributable to multiple factors including an increased focus of the CHiPs on linkage to care; increasing community acceptance and understanding of the CHiPs, and of ART and UTT, with time; increased coordination with the clinics to facilitate linkage; and clinic improvements.

BackgroundAssays 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.MethodsSamples were obtained from 220 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.ResultsThe 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.ConclusionsThe four MAAs evaluated varied in sensitivity and specificity for identifying persons infected

The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence.The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence.The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.