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Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Collins Iwuji has received research grants and honorarium for consulting services from Gilead Sciences. Dr. Diane V. Havlir reports receiving non-financial support from Gilead Sciences. All other authors declare no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Timely linkage to care and ART initiation is critical to decrease the risks of HIV-related morbidity, mortality and HIV transmission, but is often challenging. We report on the implementation and effectiveness of a linkage-to-care intervention in rural KwaZulu-Natal, South Africa., Methods: In the ANRS 12249 TasP trial on Universal Testing and Treatment (UTT) implemented between 2012-2016, resident individuals ≥16 years were offered home-based HIV testing every six months. Those ascertained to be HIV-positive were referred to trial clinics. Starting May 2013, a linkage-to-care intervention was implemented in both trial arms, consisting of tracking through phone calls and/or home visits to "re-refer" people who had not linked to care to trial clinics within three months of the first home-based referral. Fidelity in implementing the planned intervention was described using Kaplan-Meier estimation to compute conditional probabilities of being tracked and of being re-referred by the linkage-to-care team. Effect of the intervention on time to linkage-to-care was analysed using a Cox regression model censored for death, migration, and end of data follow-up., Results: Among the 2,837 individuals (73.7% female) included in the analysis, 904 (32%) were tracked at least once, and 573 of them (63.4%) were re-referred. Probabilities of being re-referred was 17% within six months of first referral and 31% within twelve months. Compared to individuals not re-referred by the intervention, linkage-to-care was significantly higher among those with at least one re-referral through phone call (adjusted hazard ratio [aHR] = 1.82; 95% confidence interval [95% CI] = 1.47-2.25), and among those with re-referral through both phone call and home visit (aHR = 3.94; 95% CI = 2.07-7.48)., Conclusions: Phone calls and home visits following HIV testing were challenging to implement, but appeared effective in improving linkage-to-care amongst those receiving the intervention. Such patient-centred strategies should be part of UTT programs to achieve the UNAIDS 95-95-95 targets., Competing Interests: CI has received honoraria for consultancy services and grant funding from Gilead Sciences unrelated to the work described in the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare no competing interests., (Copyright: © 2023 Plazy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Antiretroviral therapy (ART) has revolutionised the care of HIV-positive individuals resulting in marked decreases in morbidity and mortality, and markedly reduced transmission to sexual partners. However, these benefits can only be realised if individuals are aware of their HIV-positive status, initiated and retained on suppressive lifelong ART. Framed using the socio-ecological model, the present study explores factors contributing to poor ART uptake among community members despite high acceptance of HIV-testing within a Treatment as Prevention (TasP) trial. In this paper we identify barriers and facilitators to treatment across different levels of the socio-ecological framework covering individual, community and health system components., Methods: This research was embedded within a cluster-randomised trial (ClinicalTrials.gov, number NCT01509508) of HIV treatment as Prevention in rural KwaZulu-Natal, South Africa. Data were collected between January 2013 and July 2014 from resident community members. Ten participants contributed to repeat in-depth interviews whilst 42 participants took part in repeat focus group discussions. Data from individual interviews and focus group discussions were triangulated using community walks to give insights into community members' perception of the barriers and facilitators of ART uptake. We used thematic analysis guided by a socio-ecological framework to analyse participants' narratives from both individual interviews and focus group discussions., Results: Barriers and facilitators operating at the individual, community and health system levels influence ART uptake. Stigma was an over-arching barrier, across all three levels and expressed variably as fear of HIV disclosure, concerns about segregated HIV clinical services and negative community religious perceptions. Other barriers were individual (substance misuse, fear of ART side effects), community (alternative health beliefs). Facilitators cited by participants included individual (expectations of improved health and longer life expectancy following ART, single tablet regimens), community (availability of ART in the community through mobile trial facilities) and health system factors (fast and efficient service provided by friendly staff)., Discussion: We identified multiple barriers to achieving universal ART uptake. To enhance uptake in HIV care services, and achieve the full benefits of ART requires interventions that tackle persistent HIV stigma, and offer people with HIV respectful, convenient and efficient services. These interventions require evaluation in appropriately designed studies., Competing Interests: I have updated the competing interest statement in the text of the manuscript. Revised text below I have read the journal's policy and the authors of this manuscript have the following competing interests: CI received research grants, honoraria for consulting services and conference attendance support from Gilead Sciences. All other authors declare that they have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

In a Perspective, Collins Iwuji and Marie-Louise Newell discuss early findings from Richard Hayes and colleagues' PopART study on HIV testing and treatment.