Background:Misclassification of HIV status in population-based surveys remains a critical barrier to accurate surveillance and program evaluation. Self-reported HIV status may diverge from objective measures, particularly among individuals receiving antiretroviral therapy (ART). We used biomarker-confirmed antiretroviral (ARV) drug detection to assess the prevalence and correlates of discordance between self-reported HIV status and biologic evidence of HIV treatment among people living with HIV (PLHIV) in Zambia and South Africa. Methods:We conducted a secondary analysis of the HPTN 071 (PopART) cluster-randomized trial. At the 24-month survey visit, participants underwent HIV testing and laboratory assessment for ARV drugs in plasma. We defined discordant self-report (hereafter "non-disclosure") as reporting HIV-negative or unknown status among individuals with ARV drugs detected. We estimated the prevalence of non-disclosure, compared prevalence by study arm, and used modified Poisson regression to identify associated factors. We also examined whether non-disclosure was associated with viral suppression (<400 copies/mL). Results:Among 3,240 PLHIV with ARV drugs detected, 552 (17.0%) did not report an HIV-positive status-indicating that nearly one in six individuals on ART were misclassified by self-report. Non-disclosure did not differ between intervention and control arms (adjusted relative risk [aRR]: 1.03; 95% CI: 0.67-1.58). Non-disclosure was more common among younger individuals (age 18-24 years: aRR 2.30; 95% CI: 1.66-3.19), men (aRR: 1.39; 95% CI: 1.07-1.79), and those in formal employment (aRR: 1.42; 95% CI: 1.06-1.90). Individuals reporting condomless sex at last encounter were also more likely not to disclose (aRR: 1.59; 95% CI: 1.31-1.92). Viral suppression was high overall (93.7%) and did not differ by disclosure status (aRR: 1.06; 95% CI: 0.74-1.52). Conclusion:A substantial proportion of PLHIV receiving ART did not report a known HIV-positive status, highlighting important discordance between biomarker evidence and self-reported data. Despite high levels of viral suppression, these individuals remain "hidden" from routine surveillance, with implications for estimating HIV diagnosis and treatment coverage. Strategies that incorporate objective measures alongside self-report, and that address social and structural barriers to disclosure, are essential to improve the accuracy of HIV surveillance and guide effective public health responses.

Migrants have been identified as a population left behind by the AIDS (Acquired Immune Deficiency Syndrome) response, with evidence showing poorer HIV (Human Immunodeficiency Virus) outcomes and reduced intervention effectiveness in mobile populations. We used data from the HPTN 071 (PopART) trial (ClinicalTrials.gov number, NCT01900977) to investigate migration and HIV-related indicators, assessing whether community migration influenced PopART trial results and whether migration was associated with HIV status and position on the care continuum. The PopART trial, conducted in Zambia and South Africa (SA) from November 2013 to June 2018, evaluated a universal testing and treatment intervention using a three-arm design. A cohort of 18-44-year-olds was followed annually to estimate HIV incidence, with migration out of trial communities tracked using this cohort. migration into and within the community was tracked using intervention delivery data in community members aged 18 + . HIV-related indicators were HIV status, knowledge of HIV-positive status and ART use. Migration's influence on the trial HIV incidence results was analysed using a two-stage approach for cluster-randomised trials, adjusting for community-level migration. Associations between HIV-related indicators and both out-migration (Poisson regression using cohort data) and in-migration (logistic regression using cross-sectional data) were also estimated. While migration differed between trial arms, there was no evidence that it confounded the intervention effect on HIV incidence. There was evidence out-migration was higher among HIV-positive individuals who did not know (or did not disclose) their HIV-positive status compared to those HIV-negative (adjusted rate ratio: Zambia 1.28, 95%CI 1.17-1.39; SA 1.27, 95%CI 1.17-1.38). Residents who had moved into the community within the previous year were less likely to be aware of their HIV-positive status than longer-term residents (adjusted odds ratio: Zambia 0.18, 95%CI 0.16-0.19; SA 0.23, 95%CI 0.20-0.28) and contributed to approximately one in four of the newly identified HIV infections. Following intervention delivery the gap in knowledge of HIV status and ART treatment coverage between recent in-migrants and longer-term residents closed. Countries with high HIV burden should aim to ensure a sustained delivery of HIV services in areas with high levels of population mobility and in areas with moderate to high HIV prevalence.

Background: HIV incidence in sub-Saharan Africa has declined substantially since 2000 according to epidemic estimates published by UNAIDS. These estimates, derived by fitting mathematical models to national surveillance data, guide HIV programmes and epidemic response strategies. We assessed whether the level and age distribution of HIV incidence from modelled estimates were consistent with empirical HIV incidence observations, and whether incidence levels and trends were systematically different between study types, populations, and age groups. Methods: We conducted an updated systematic review of adult HIV incidence data from sub-Saharan Africa published July 2019-February 2024 by searching Scopus, PubMed, Embase, and OVID databases, and combined with earlier systematic review data. We matched empirical incidence measurements between 1990-2023 to UNAIDS HIV incidence estimates by study area, sex, age group, and year. We used Bayesian mixed-effect Poisson regression to estimate (1) incidence rate ratios (IRR) between empirical observations and matched modelled incidence estimates adjusted for sex, year and study type/population; and (2) time trends in age-specific incidence from population-based cohort studies and household surveys. Results: 3560 HIV empirical incidence measurements were included from 179 studies conducted in 21 countries, comprising 23,000 new infections and 3.1 million person-years. Incidence observations from nationally-representative household surveys (IRR 1.07 95%CI 0.68, 1.67) and population-representative study populations (IRR 0.98 95%CI 0.51, 1.89) were not significantly different from matched modelled estimates, and declined at the same rate as modelled estimates (annual aRR 0.99 95%CI 0.98, 1.01). Studies among pregnant women (IRR 2.60 95%CI 1.58, 4.28), control arms of clinical trials (IRR 3.01 95%CI 1.90, 4.77) and key populations (FSW IRR: 6.46 95%CI 4.18, 10.00; MSM 44.02 95%CI 27.35, 70.87) had significantly higher incidence than modelled total population incidence estimates. Across population cohorts in Eastern and Southern Africa, HIV incidence among adults aged 15-49 declined by 75-90% between 2010-2023, and declined 7% (95%CI 4-10%) faster per year among young adults 15-24 compared to age 25+ years. Modelled incidence declined similarly to cohort data, but did not reflect the aging of the epidemic. Conclusion: Observed incidence in population-representative studies in sub-Saharan Africa has declined steeply. Mathematical models that infer incidence from cross-sectional HIV surveillance data estimated the same incidence level and decline over time as population-representative studies. Studies with non-representative inclusion criteria had significantly higher incidence, including those among pregnant women and most HIV prevention/vaccine efficacy trials. The age pattern of incidence in modelled estimates should be reconsidered to capture the aging of the epidemic indicated by cohort studies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded by UNAIDS. OS and JWI-E acknowledge funding support from the Bill and Melinda Gates Foundation (INV-005576), and the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. The study sponsor(s) had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research Ethics Committee of Imperial College London gave ethical approval for this work (Reference number: 7045035) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Analytical datasets are available at https://zenodo.org/records/18482588.

Abstract While much progress has been made in reducing the incidence of HIV-1 infection in sub-Saharan Africa in recent years, bringing the epidemic to an end will require identification of the demographic groups that continue to contribute to transmission. Pathogen phylogenetics and individual-based mathematical models (IBMs) of transmission are approaches that enable researchers to explore such questions. Here, we used both methods to characterise the ages and sexes of the individuals involved in heterosexual transmission in the context of the HPTN 071 (PopART) trial in Zambia. The results were concordant, and show that the male partner was on average older than the female by less than seven years, with larger age gaps in male-to-female than female-to-male transmissions. We found that the largest gaps for female recipients were amongst the youngest of those recipients. Conversely, the youngest male recipients saw the smallest gaps. We further used the IBM to demonstrate that transmission to new age cohorts first entering into sexual activity is driven predominantly by male-to-female transmission. We also simulated the PopART universal testing and treatment intervention into the future to show that effective treatment of under-35-year-olds accounts for 93.8% of the reduction in incidence by 2039, while effective treatment of under-35-year-old men accounts for 62.1%. Finally, we simulated a one-year cessation of ART treatment for the whole population, which resulted in an immediate increase in the average age at transmission of both sources and recipients. With it becoming ever more expensive and difficult to find treatment-naive individuals and link them to care, targeted interventions for demographic groups such as under-35 men may be the key to finally ending HIV.

Background:Herpes simplex virus type 2 (HSV2) is an important cofactor for HIV acquisition and transmission. Associations between the infections are reexamined in longitudinal data from an HIV prevention trial. Methods:The HPTN 071 (PopART) trial evaluated a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV incidence was measured in a cohort of approximately 2000 adults (age, 18-44 years) selected randomly from each community and followed up for 36 months. Incidence of HSV2 infection was estimated, and the effects of risk factors were examined. The association between HIV incidence and HSV2 infection was examined at individual and community levels. Results:An overall 10 539 participants were HSV2 negative at baseline and retested after 36 months. Estimated HSV2 incidence was 5.4 per 100 person-years (95% CI, 5.0-5.7) for women and 2.9 per 100 person-years (95% CI, 2.6-3.2) for men. When compared with those remaining HSV2 negative, HIV incidence was higher in those who were HSV2 positive at baseline (women: adjusted rate ratio [aRR], 3.24 [95% CI, 2.50-4.20]; men: aRR, 2.57 [95% CI, 1.60-4.11]) and even higher in those who seroconverted to HSV2 during follow-up (women: aRR, 5.94 [95% CI, 4.42-7.98]; men: aRR, 8.37 [95% CI, 5.18-13.52]). At the community level, strong associations were seen between HIV incidence and HSV2 prevalence (R 2 = 0.48, P < .001) and incidence (R 2 = 0.36, P = .004). Conclusions:There were strong associations between HIV incidence and HSV2 prevalence and incidence at individual and community levels. HSV2 control could contribute to HIV prevention.

TRIAL REGISTRATION:ClinicalTrials.gov NCT01900977.

Background The World Health Organization suggest that systematic tuberculosis (TB) screening may be conducted in high prevalence settings (>0.5%), though supporting evidence is limited. Methods Between January-2014 to December-2017, the HPTN 071 (PopART) cluster-randomized trial implemented universal HIV and TB testing across 21 communities in Zambia and South Africa (SA), with TB prevalence of 0.5% and 1.6%, respectively. Trained community health workers visited households annually to offer HIV testing and TB symptom screening, with sputum collection from individuals who screened positive. Diagnostic testing used Xpert-MTB/RIF or smear microscopy, and linkage to treatment was facilitated. We analysed TB screening and diagnosis data across three rounds (R1–R3) in Zambia and R3 in SA, where complete data were available. We examined factors associated with reporting TB symptoms and being diagnosed with TB. Results The yield of newly diagnosed TB (per 100,000 persons) increased across rounds in Zambia [R1 = 81, R2 = 93, R3 = 110; p-value (trend) = 0.003] and was higher in R3 SA (380). In R3, TB yield was higher in men (Zambia: 146; SA: 543) than women (Zambia: 76; SA: 257), and among newly diagnosed HIV-positive individuals (Zambia: 541; SA: 789) compared to HIV-negative individuals (Zambia: 48; SA: 170) and self-reported HIV-positive individuals on ART (Zambia: 105; SA: 192). In Zambia R3, participants screened twice before had 38% lower odds of being diagnosed with TB compared to those screened first time [Adjusted odds ratio = 0.62, 95% CI (0.43, 0.90)]. Conclusion The PopART intervention identified undiagnosed TB through systematic TB symptom screening, particularly in men and newly diagnosed HIV-positive individuals and individuals who had not previously been screened. Yield was relatively low compared to estimated TB prevalence. Trial registration [ClinicalTrials.gov][1] NCT01900977 ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT01900977 ### Funding Statement This work was supported by the National Institute of Allergy and Infectious Diseases, the US President’s Emergency Plan for AIDS Relief, the International Initiative for Impact Evaluation, the Bill and Melinda Gates Foundation, the National Institute on Drug Abuse, and the National Institute of Mental Health. The content herein is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the ethics committees of the London School of Hygiene & Tropical Medicine, the University of Zambia, and Stellenbosch University. Additional Institutional Review Board approvals were given for including those aged 15 years and older in later rounds. Individuals gave informed verbal consent to participate in the intervention and informed written or witnessed consent for HIV testing. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes We will provide aggregate data sufficient to replicate the main analyses presented in this paper. These aggregate data will include counts of tuberculosis screening and diagnostic outcomes stratified by country, round, trial arm, community, gender, age group, HIV status, and participation in previous screening rounds. The protocol approved by the ethics committees specifies that intervention data can only be shared in aggregate form. For queries related to these data, the PI of the HPTN Statistical Data Management Centre (SDMC), Deborah Donnell (deborah{at}scharp.org), can be contacted. [1]: http://ClinicalTrials.gov

INTRODUCTION:HPTN 084 found that long-acting cabotegravir (CAB-LA) was well-tolerated and significantly reduced the risk of HIV acquisition in women compared to tenofovir disoproxil fumarate/emtricitabine (F/TDF). During the blinded phase of the trial, participants were required to use an effective method of contraception, including an injectable or implantable hormonal contraceptive (HC) agent. A contraceptive sub-study assessed the pharmacokinetic interactions between pre-exposure prophylaxis agents (CAB-LA or F/TDF) and etonogestrel (ENG), medroxyprogesterone acetate (MPA) or norethindrone enanthate (NET-EN). METHODS:Participants were enrolled in a nested sub-study between 24 February 2020 and 26 October 2020. Via a convenience sampling strategy, plasma concentrations of ENG, MPA and NET-EN were evaluated at enrolment and weeks 25, 49 and 73; plasma tenofovir (TFV) and CAB concentrations were determined at contemporaneous visits. Participants were allowed to switch contraceptives, and HC assessments were adjusted accordingly. Geometric mean concentrations were calculated and compared using t-tests or Fisher's exact tests. RESULTS:One hundred and seventy participants were included in this analysis. Hormone concentrations at all study visits were comparable between the CAB-LA and F/TDF study arms. Among participants randomized to the CAB-LA arm, geometric mean concentrations declined from enrolment to the follow-up period for ENG (335 to 202 pg/ml), MPA (1520 to 1138 pg/ml) and NET-EN (3715 to 1888 pg/ml); similar findings were observed among participants randomized to the F/TDF arm. Observed HC declines are likely attributed to the timing of contraceptive administration relative to sampling; the percentage of participants with hormone concentrations above thresholds associated with ovulation suppression was high (73-100%) and did not differ between arms. CAB concentrations were comparable across contraceptive types, with 97.8-98.1% of participants yielding trough CAB concentrations above the protocol-specified target threshold. TFV concentrations were unquantifiable for most participants, irrespective of contraceptive agent, rendering comparisons largely uninformative. CONCLUSIONS:Given the comparable hormone concentrations between arms and the likely influence of the timing of sample collection on observed measurements, clinically significant interactions between CAB-LA and HC are not expected. Associations between F/TDF and hormone concentrations could not be effectively evaluated due to low adherence to F/TDF. CLINICAL TRIAL REGISTRATION:NCT0316456.

HPTN 071 (PopART) implemented a comprehensive HIV prevention package which aimed to reduce HIV incidence within 21 communities of Zambia and South Africa: Arm A, PopART intervention of universal HIV testing and treatment; Arm B, PopART intervention of universal HIV testing with ART provided according to local guidelines; and Arm C, standard of care. Analyses so far have not accounted for the sampling design of the enrolled cohort. We performed a sample-weighted re-analysis of the primary outcome of the PopART trial to derive a population-based estimate of the intervention effect. Enrollment used a two-stage sampling design: household and adult participant within each household. We constructed post-stratification weights to match the age and sex distribution of the target population in these communities. Weighted Poisson regression was used to estimate community-level HIV incidence. The PopART intervention effect was estimated using log-transformed community-level incidence estimates in an ANCOVA model. The analysis based on community-level incidence shows a 25

The HIV epidemic in sub-Saharan Africa is historically characterised by high levels of prevalence and incidence. With the global effort to reach UNAIDS 95-95-95 targets, the scaling-up of HIV treatment, and focused preventive interventions, incidence has been declining over the past decade, albeit non-consistently across different sex and age groups. Two questions remain to be addressed to help tailor setting-specific interventions and allocate resources optimally. Firstly, are there unidentified demographic groups that are sources of transmission? Secondly, what are the patterns of decline in incidence across different groups? Model-based assessment is a valuable tool for the design of focused interventions and to answer these questions. PopART-IBM, an individual-based model calibrated to (anonymised) age-and-sex stratified data, was developed in the context of the HPTN-071 (PopART) trial, and it offers a unique opportunity to explore such questions in the context of high-burden HIV communities in Zambia and South Africa. The outputs of the model include the full HIV transmission and partnership networks. In this work, we explore these and show that the sexual partnership network exhibits a large connected component, usually comprising over 40 % of the population, in each of the studied communities. An analysis of the large connected component reveals that it is formed by young people (20-40 years old) and is centered around the most sexually active individuals of the community. At the same time, many individuals in the large connected component only have one partner, highlighting the complex dynamics of risk correlations in a population. Inspecting the transmission network reveals that, on average, more than 80% of transmissions occur among individuals belonging to the large connected component. These findings indicate that populations consisting of young and highly sexually active individuals should be given high priority when designing or deploying interventions.

INTRODUCTION:HIV Prevention Trials Network (HPTN) 071 (PopART) was a cluster-randomized trial to evaluate universal testing and treatment (UTT) strategies for HIV prevention. HPTN071 compared three arms: (A) combination prevention with UTT; (B) combination prevention with universal testing and antiretroviral therapy initiation according to local guidelines; and (C) standard of care (SOC). Interventions were implemented in entire randomized communities, with impacts on HIV incidence measured in "population cohorts," that is the HPTN071 sample. Unexpectedly, a significantly lower incidence was not observed in arm A relative to SOC. Importantly, rates of participation in the HPTN071 sample differed among population subgroups, for example men were underrepresented. METHODS:To correct for underrepresented subgroups, PopART intervention effects are estimated in a population of interest, adults aged 18-44 in trial provinces, characterized with two nationally representative HIV-focused surveys. The HPTN071 sample is weighted to match the population of interest by demographics and HIV risk factors. Risk of HIV acquisition is compared across arms, both in the trial population (unweighted) and the population of interest (weighted). Both (1) the risk of HIV acquisition between 1 and 3 years and (2) the risk of HIV acquisition by 3 years are compared. RESULTS:In the trial population, estimated risk in arm A is, counterintuitively, slightly higher than SOC (Year 1-3 Risk Difference [RD]: 0.10%; 95% CI: -1.15%, 1.25%). After weighting, risk in arm A is lower than SOC in the population of interest (RD: -0.34%; 95% CI: -2.04%, 0.96%). Weighting also strengthened the estimated effect in arm B relative to SOC (unweighted RD: -0.66%, 95% CI: -1.88%, 0.46%; weighted RD: -1.18%, 95% CI: -2.85%, 0.15%). Weighted year 3 risk difference estimates indicated even stronger possible intervention effects: A versus SOC -0.83% (95% CI: -2.94%, 0.99%), B versus SOC -1.86% (95% CI: -3.80%, -0.09%). CONCLUSIONS:PopART interventions are estimated to be more protective in the population of interest than observed in the HPTN071 sample. These results partially explain the unexpected finding in arm A, providing further support for UTT strategies for HIV prevention. This analysis also highlights the importance of considering heterogeneous treatment effects among population subgroups when measuring the overall efficacy of HIV interventions.

Across sub-Saharan Africa, stigma levels have been decreasing but not enough to achieve the 95-95-95 HIV targets by 2030. Current global HIV frameworks have identified stigma reduction, context specific interventions, and community mobilization as critical to enabling more effective uptake of HIV services. We conducted a retrospective analysis of longitudinal qualitative and quantitative data collected in 21 urban communities in Zambia and South Africa involved in the HPTN071 (PopART) trial between 2014 and 2019. We illustrate in four communities how three sociostructural features of communities intersected with stigma at the community level: intergroup tensions, the community responses to sociodemographic change, and the local history of HIV initiatives. Tension between different social groups often functioned as a catalyst for stigmatizing attitudes. Sociodemographic change at community level took the form of rapid housing development, population expansion, and outsiders moving in. The ability and willingness of a community to respond to this sociodemographic change and antistigma initiatives influenced HIV stigma. Our findings illustrate patterns in how community-level dynamics influence the trajectory of stigma and point toward a key strategy for accelerating reductions in stigma across sub-Saharan Africa. Community-led approaches, which take local context and dynamics into account, are critical to address the societal enablers of HIV, including eliminating stigma and discrimination. Further, stigma-reduction activities should build on community HIV history, be sensitive to involuntary disclosure, speak to "othering" linked to intergroup tensions, and be a consistent component of HIV programming, given the protection such programming provides against stigma and discrimination.

Abstract Background In the high disease burden and resource-constrained contexts of sub-Saharan Africa (SSA), health workers experience a range of psychosocial stressors that leave them vulnerable to developing burnout, which can reduce service quality and negatively impact their own health and wellbeing. As universal testing and treatment (UTT) for HIV scales up across SSA, we sought to understand the implications of this human resource-intensive approach to HIV prevention to inform decision-making about health workforce staffing and support needs. Methods Using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS), we assessed the prevalence of three domains of burnout—emotional exhaustion, depersonalization, and personal accomplishment—among three cadres of health workers delivering health services in areas receiving a UTT intervention in Zambia and South Africa. These cadres included health facility workers (n = 478), community health workers (n = 159), and a study-specific cadre of community HIV care providers (n = 529). We used linear regression to assess risk factors associated with emotional exhaustion, the only domain with sufficient variation in our sample. Results The MBI-HSS was completed by 1499/2153 eligible participants (69.6% response rate). Less than 1% of health workers met Maslach’s definition for burnout. All groups of health workers reported lower levels of emotional exhaustion than found in previous studies of this type (mean score scores ranged from 10.7 to 15.4 out of 54 across health cadres). Higher emotional exhaustion was associated with higher educational attainment (βadj = 2.24, 95% CI 0.76 to 3.72), greater years providing HIV services (βadj = 0.20, 95% CI 0.03 to 0.36), and testing negative for HIV at last HIV test (βadj = − 3.88 − 95% CI 5.69 to − 2.07). Working as a CHW was significantly associated with lower emotional exhaustion (βadj = − 2.52, 95% CI − 4.69 to − 0.35). Among all health workers, irrespective of HIV status, witnessing stigmatizing behaviors towards people living with HIV among their co-workers was associated with significantly increased emotional exhaustion (βadj = 3.38, 95% CI 1.99 to 4.76). Conclusions The low level of burnout detected among health workers is reassuring. However, it remains important to assess how UTT may affect levels of emotional exhaustion among health workers over time, particularly in the context of emerging global pandemics, as burnout may impact the quality of HIV services they provide and their own mental health and wellbeing. Interventions to reduce HIV stigma in health facilities may protect against emotional exhaustion among health workers, as well as interventions to increase mindfulness and resilience among health workers at risk of burnout. Trial registration ClinicalTrials.gov number: NCT01900977.

Transfeminine women (assigned male sex at birth and identifying with a feminine gender identity) are at risk for intersectional stigma related to their gender, sexual orientation, and other parts of their social identities (including age, class, and race). These layered stigmas can result in increased physical and mental health concerns related to physical and emotional violence, substance use, high risk sexual behaviour and HIV exposure. Social networks are important support structures for transfeminine women to ameliorate imposed risk and stigma. We investigated the family networks, household structures and community support systems of eight transfeminine women in the Western Cape, South Africa. The data for this study are embedded in a qualitative component of the larger HPTN 071 (PopART) trial. Data included in-depth interview transcripts, genogram activities and community map drawings. We found that participants who were not living in a supportive family and household structure faced stigma and health risks. In addition, we found examples of how transfeminine women in unsupportive social situations constructed their own family and household unit for support. Our findings agree with those of other studies in that transgender people often rely on extended family members, friends, or peers as social support when their families do not support or ostracise them. Understanding how transfeminine women re-organise social units to be better supported is important so that better health services can be provided to them in the local South African and international context. Further research on family re-structuring among gender and sexual minority groups is needed.

AbstractPeople living with HIV (PLHIV) report lower health-related quality-of-life (HRQoL) than HIV-negative people. HIV stigma may contribute to this. We explored the association between HIV stigma and HRQoL among PLHIV. We used cross-sectional data from 3991 randomly selected PLHIV who were surveyed in 2017–2018 for HPTN 071 (PopART), a cluster randomised trial in Zambia and South Africa. Participants were 18–44 years, had laboratory-confirmed HIV infection, and knew their status. HRQoL was measured using the EuroQol-5-dimensions-5-levels (EQ-5D-5L) questionnaire. Stigma outcomes included: internalised stigma, stigma experienced in the community, and stigma experienced in healthcare settings. Associations were examined using logistic regression. Participants who had experienced community stigma (n = 693/3991) had higher odds of reporting problems in at least one HRQoL domain, compared to those who had not (adjusted odds ratio, aOR: 1.51, 95% confidence interval, 95% Cl: 1.16–1.98, p = 0.002). Having experienced internalised stigma was also associated with reporting problems in at least one HRQoL domain (n = 552/3991, aOR: 1.98, 95% CI: 1.54–2.54, p < 0.001). However, having experienced stigma in a healthcare setting was less common (n = 158/3991) and not associated with HRQoL (aOR: 1.04, 95% CI: 0.68–1.58, p = 0.850). A stronger focus on interventions for internalised stigma and stigma experienced in the community is required.

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.

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 ≤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.