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. 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. 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. 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.)

In South Africa, HIV prevalence among youth aged 15-24 is among the world's highest. Given the urgent need to identify effective HIV prevention approaches, this review assesses the evidence base for youth HIV prevention in South Africa.

Multidrug-resistant (MDR) tuberculosis (TB) presents a challenge for global TB control. Treating individuals with MDR-TB infection to prevent progression to disease could be an effective public health strategy. Young children are at high risk of developing TB disease following infection and are commonly infected by an adult in their household. Identifying young children with household exposure to MDR-TB and providing them with MDR-TB preventive therapy could reduce the risk of disease progression. To date, no trials of MDR-TB preventive therapy have been completed and World Health Organization guidelines suggest close observation with no active treatment. The tuberculosis child multidrug-resistant preventive therapy (TB-CHAMP) trial is a phase III cluster randomised placebo-controlled trial to assess the efficacy of levofloxacin in young child contacts of MDR-TB cases. The trial is taking place at three sites in South Africa where adults with MDR-TB are identified. If a child aged < 5 years lives in their household, we assess the adult index case, screen all household members for TB disease and evaluate any child aged < 5 years for trial eligibility. Eligible children are randomised by household to receive daily levofloxacin (15–20 mg/kg) or matching placebo for six months. Children are closely monitored for disease development, drug tolerability and adverse events. The primary endpoint is incident TB disease or TB death by one year after recruitment. We will enrol 1556 children from approximately 778 households with an average of two eligible children per household. Recruitment will run for 18–24 months with all children followed for 18 months after treatment. Qualitative and health economic evaluations are embedded in the trial. If the TB-CHAMP trial demonstrates that levofloxacin is effective in preventing TB disease in young children who have been exposed to MDR-TB and that it is safe, well tolerated, acceptable and cost-effective, we would expect that that this intervention would rapidly transfer into policy. ISRCTN Registry, ISRCTN92634082 . Registered on 31 March 2016.

Stigma is a critical barrier for TB care delivery; yet data on stigma reduction interventions is limited. This review maps the available literature on TB stigma reduction interventions, using the Health Stigma and Discrimination framework and an implementation analysis to identify research gaps and inform intervention design. Using search terms for TB and stigma, we systematically searched PubMed, EMBASE and Web of Science. Two independent reviewers screened all abstracts, full-texts, extracted data, conducted a quality assessment, and assessed implementation. Results were categorized by socio-ecological level, then sub-categorized by the stigma driver or manifestation targeted. After screening 1865 articles, we extracted data from nine. Three studies were implemented at the individual and interpersonal level using a combination of TB clubs and interpersonal support to target internal and anticipated stigma among persons with TB. Two studies were implemented at the interpersonal level using counselling or a video based informational tool delivered to households to reduce stigma drivers and manifestations. Three studies were implemented at the organizational level, targeting drivers of stigma among healthcare workers (HW) and enacted stigma among HWs. One study was implemented at the community level using an educational campaign for community members. Stakeholder consultation emphasized the importance of policy level interventions and education on the universality of risk to destigmatize TB. Review findings suggest that internal and anticipated TB stigma may be addressed effectively with interventions targeted towards individuals using counselling or support groups. In contrast, enacted TB stigma may be better addressed with information-based interventions implemented at the organizational or community level. Policy level interventions were absent but identified as critical by stakeholders. Implementation barriers included the lack of high-quality training and integration with mental health services. Three key gaps must be addressed in future research: consistent stigma definitions, standardized stigma measurement, and measurement of implementation outcomes.

To achieve UNAIDS 90:90:90 targets at population-level, knowledge of HIV status must be followed by timely linkage to care, initiation and maintenance of antiretroviral therapy (ART) for all people living with HIV (PLHIV). Interpreting quantitative patterns using qualitative data, we investigate time taken to link to care and initiate ART amongst individuals aware of their HIV-status in high HIV-prevalence urban communities in the HPTN 071 (PopART) study, a community-randomised trial of a combination HIV prevention package, including universal testing and treatment, in 21 communities in Zambia and South Africa. Data are drawn from the seven intervention communities where immediate ART irrespective if CD4 count was offered from the trial-start in 2014. Median time from HIV-diagnosis to ART initiation reduced after 2 years of delivering the intervention from 10 to 6 months in both countries but varied by gender and community of residence. Social and health system realities impact decisions made by PLHIV about ART initiation.

Health workers in 21 government health facilities in Zambia and South Africa linked spatial organisation of HIV services and material items signifying HIV-status (for example, coloured client cards) to the risk of People Living with HIV (PLHIV) 'being seen' or identified by others. Demarcated HIV services, distinctive client flow and associated-items were considered especially distinguishing. Strategies to circumvent any resulting stigma mostly involved PLHIV avoiding and/or reducing contact with services and health workers reducing visibility of PLHIV through alterations to structures, items and systems. HIV spatial organisation and item adjustments, enacting PLHIV-friendly policies and wider stigma reduction initiatives could combined reduce risks of identification and enhance the privacy of health facility space and diminish stigma.