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Background: Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial randomised 14 communities to receive the "PopART" intervention during 2014 to 2017 (7 arm A and 7 arm B communities) and 7 communities to receive standard-of-care (arm C). The intervention was delivered door-to-door by community HIV care providers (CHiPs) and included universal HIV testing, facilitated linkage to HIV care at government health clinics, and systematic TB symptom screening. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study aimed to measure the impact of delivering the PopART intervention on TB outcomes, in communities with high HIV and TB prevalence. Methods and findings: The study population of the HPTN 071 (PopART) trial included individuals aged ≥15 years living in 21 urban and peri-urban communities in Zambia and South Africa, with a total population of approximately 1 million and an adult HIV prevalence of around 15% at the time of the trial. Two sputum samples for TB testing were provided to CHiPs by individuals who reported ≥1 TB suggestive symptom (a cough for ≥2 weeks, unintentional weight loss ≥1.5 kg in the last month, or current night sweats) or that a household member was currently on TB treatment. Antiretroviral therapy (ART) was offered universally at clinics in arm A and according to local guidelines in arms B and C. The TREATS study was conducted in the same 21 communities as the HPTN 071 (PopART) trial between 2017 and 2022, and TB prevalence was a co-primary endpoint of the TREATS study. The primary comparison was between the PopART intervention (arms A and B combined) and the standard-of-care (arm C). During 2019 to 2021, a TB prevalence survey was conducted among randomly selected individuals aged ≥15 years (approximately 1,750 per community in arms A and B, approximately 3,500 in arm C). Participants were screened on TB symptoms and chest X-ray, with diagnostic testing using Xpert-Ultra followed by culture for individuals who screened positive. Sputum eligibility was determined by the presence of a cough for ≥2 weeks, or ≥2 of 5 "TB suggestive" symptoms (cough, weight loss for ≥4 weeks, night sweats, chest pain, and fever for ≥2 weeks), or chest X-ray CAD4TBv5 score ≥50, or no available X-ray results. TB prevalence was compared between trial arms using standard methods for cluster-randomised trials, with adjustment for age, sex, and HIV status, and multiple imputation was used for missing data on prevalent TB. Among 83,092 individuals who were eligible for the survey, 49,556 (59.6%) participated, 8,083 (16.3%) screened positive, 90.8% (7,336/8,083) provided 2 sputum samples for Xpert-Ultra testing, and 308 (4.2%) required culture confirmation. Overall, estimated TB prevalence was 0.92% (457/49,556). The geometric means of 7 community-level prevalence estimates were 0.91%, 0.70%, and 0.69% in arms A, B, and C, respectively, with no evidence of a difference comparing arms A and B combined with arm C (adjusted prevalence ratio 1.14, 95% confidence interval, CI [0.67, 1.95], p = 0.60). TB prevalence was higher among people living with HIV than HIV–negative individuals, with an age-sex-community adjusted odds ratio of 2.29 [95% CI 1.54, 3.41] in Zambian communities and 1.61 [95% CI 1.13, 2.30] in South African communities. The primary limitations are that the study was powered to detect only large reductions in TB prevalence in the intervention arm compared with standard-of-care, and the between-community variation in TB prevalence was larger than anticipated. Conclusions: There was no evidence that the PopART intervention reduced TB prevalence. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of several years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB. Trial registration: The TREATS study was registered with ClinicalTrials.gov Identifier: NCT03739736 on November 14, 2018. The HPTN 071 (PopART) trial was registered at ClinicalTrials.gov under number NCT01900977 on July 17, 2013. In a population based cohort study, Eveline Klinkenberg and colleagues examine the impact of the PopART intervention on TB prevalence in Zambia and South Africa. Author summary: Why was this study done?: Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) community-randomised trial, conducted in 21 Zambian and South African communities (2013 to 2018), provided an opportunity to test whether the PopART intervention—universal testing and universal treatment for HIV combined with universal symptom screening for TB—could reduce TB prevalence. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study measured the impact of the PopART intervention on TB prevalence, comparing 14 communities that received the PopART intervention during 2014 to 2017 with 7 communities that received standard-of-care. What did the researchers do and find?: We conducted a TB prevalence survey during 2019 to 2021, among around 50,000 randomly selected individuals aged ≥15 years in the 21 urban and peri-urban communities that were included in the HPTN 071 (PopART) trial. Overall, estimated TB prevalence was 0.92% (457/49,556). There was no evidence of a difference in TB prevalence between the PopART intervention and standard-of-care communities, with an adjusted prevalence ratio of 1.14, 95% confidence interval (CI) [0.67, 1.95]. TB prevalence was around 2 times higher among HIV–positive than HIV–negative individuals, adjusted for age, sex, and community, and several times higher among men than women. What do these findings mean?: This study found no evidence that the PopART intervention reduced TB prevalence, compared with standard-of-care. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of a few years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB, and several years of delivering such a strategy might be able to achieve a considerable reduction in TB prevalence. [ABSTRACT FROM AUTHOR]

Background Antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission risk. The primary aim of this study was to evaluate ART uptake in a trial in Zambia and South Africa that implemented a community-wide universal testing and treatment package to reduce HIV incidence. Methods Study communities were randomized to 3 arms: A, combination-prevention intervention with universal ART; B, combination-prevention intervention with ART according to local guidelines; and C, standard of care. Samples were collected from people with HIV (PWH) during a survey visit conducted 2 years after study implementation: these samples were tested for 22 antiretroviral (ARV) drugs. Antiretroviral therapy uptake was defined as detection of ≥1 ARV drug. Resistance was evaluated in 612 randomly selected viremic participants. A 2-stage, cluster-based approach was used to assess the impact of the study intervention on ART uptake. Results Antiretroviral drugs were detected in 4419 of 6207 (71%) samples (Arm A, 73%; Arm B, 70%; Arm C, 60%); 4140 (94%) of samples with ARV drugs had viral loads <400 copies/mL. Drug resistance was observed in 237 of 612 (39%) viremic participants (95 of 102 [93%] with ARV drugs; 142 of 510 [28%] without drugs). Antiretroviral therapy uptake was associated with older age, female sex, enrollment year, seroconverter status, and self-reported ART (all P <.001). The adjusted risk ratio for ART uptake was similar for Arm A versus C (1.21; 95% confidence interval [CI],.94–1.54; P =.12) and Arm B versus C (1.14; 95% CI,.89–1.46; P =.26). Conclusions At the 2-year survey, 71% of PWH were on ART and 94% of those participants were virally suppressed. Universal testing and treatment was not significantly associated with increased ART uptake in this cohort. [ABSTRACT FROM AUTHOR]

Background: The HPTN 071 (PopART) trial implemented universal test and treat (UTT) in three clinics in the Western Cape, South Africa at a time when antiretroviral treatment (ART) was only offered by CD4 threshold and World Health Organization clinical staging. This required a concomitant shift in the way health workers communicated ART initiation messages. We provide insight into front-line ART initiation communication pre-national policy shift. Method: The design of this study was exploratory with a case descriptive analysis of ART initiation in three clinics. To characterise their demographic profiles, we reviewed 134 randomly selected patient clinical folders of people who initiated ART at CD4 counts greater than the recommended standard. Further, we conducted 12 key informant interviews with health workers at these facilities and thematically analysed health workers' responses. Results: The median age of patients initiating ART regardless of CD4 count (above the threshold level) was 33 years and most were women (73.9%), married (76.1%), and unemployed (48.5%). The median CD4 count of patients initiating outside guidelines was 566.5 cells/µl. Contrary to expectations, key informants indicated no radical shift in messaging to explain ART initiation regardless of CD4 count. Rather, they encouraged people living with HIV (PLHIV) to initiate ART while they still "feel well". The reduced risk of onward HIV transmission did not factor significantly in how health workers motivated clients. Conclusion: Motivating PLHIV to initiate ART regardless of CD4 count in high burden settings is possible. However, there are still opportunities to improve messaging about immediate ART initiation or at high CD4 counts for the prevention of onward transmission. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Introduction: WHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/μL for the HPTN 071 (PopART) trial. Methods: All clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as ‘being three or more months late for an antiretroviral pharmacy pick-up appointment’. All clients were followed until attrition, transfer out or end May 2016. Results: A total of 2423 clients with a median baseline CD4 count of 328 cells/μL (IQR 195–468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8–42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/μL compared to those with baseline CD4 counts of 0–500 cells/μL (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months. Conclusions: Attrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/μL. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/μL, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries. [ABSTRACT FROM AUTHOR]

Introduction: HPTN 071 (PopART) is a three-arm community randomized trial in Zambia and South Africa evaluating the impact of a combination HIV prevention package, including universal test and treat (UTT), on HIV incidence. This nested study examined factors associated with timely linkage-to-care and ART initiation (TLA) (i.e. within six-months of referral) in the context of UTT within the intervention communities of the HPTN 071 (PopART) trial. Methods: Of the 7572 individuals identified as persons living with HIV (PLWH) (and not on antiretroviral treatment (ART)) during the first year of the PopART intervention provided by Community HIV-care Providers (CHiPs) through door-to-door household visits, individuals who achieved TLA (controls) and those who did not (cases), stratified by gender and community, were randomly selected to be re-contacted for interview. Standardized questionnaires were administered to explore factors potentially associated with TLA, including demographic and behavioural characteristics, and participants' opinions on HIV and related services. Odds ratios comparing cases and controls were estimated using a multi-variable logistic regression. Results: Data from 705 participants (333 cases/372 controls) were analysed. There were negligible differences between cases and controls by demographic characteristics including age, marital or socio-economic position. Prior familiarity with the CHiPs encouraged TLA (aOR of being a case: 0.58, 95% CI: 0.39 to 0.86, p = 0.006). Participants who found clinics overcrowded (aOR: 1.51, 95% CI: 1.08 to 2.12, p = 0.006) or opening hours inconvenient (aOR: 1.63, 95% CI: 1.06 to 2.51, p = 0.02) were less likely to achieve TLA, as were those expressing stronger feelings of shame about having HIV (ptrend = 0.007). Expressing "not feeling ready" (aOR: 2.75, 95% CI: 1.89 to 4.01, p < 0.001) and preferring to wait until they felt sick (aOR: 2.00, 95% CI: 1.27 to 3.14, p = 0.02) were similarly indicative of being a case. Worrying about being seen in the clinic or about how staff treated patients was not associated with TLA. While the association was not strong, we found that the greater the number of self-reported lifetime sexual partners the more likely participants were to achieve TLA (ptrend = 0.06). There was some evidence that participants with HIV-positive partners on ART were less likely to be cases (aOR: 0.75, 95% CI: 0.53 to 1.06, p = 0.07). Discussion: The lack of socio-demographic differences between cases and controls is encouraging for a "universal" intervention that seeks to ensure high coverage across whole communities. Making clinics more "patient-friendly" could enhance treatment uptake further. The finding that those with higher risk behaviour are more actively engaging with UTT holds promise for treatment-as-prevention. [ABSTRACT FROM AUTHOR]

Background: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets require that, by 2020, 90% of those living with HIV know their status, 90% of known HIV-positive individuals receive sustained antiretroviral therapy (ART), and 90% of individuals on ART have durable viral suppression. The HPTN 071 (PopART) trial is measuring the impact of a universal testing and treatment intervention on population-level HIV incidence in 21 urban communities in Zambia and South Africa. We report observational data from four communities in Zambia to assess progress towards the UNAIDS targets after 1 y of the PopART intervention.Methods and Findings: The PopART intervention comprises annual rounds of home-based HIV testing delivered by community HIV-care providers (CHiPs) who also support linkage to care, ART retention, and other services. Data from four communities in Zambia receiving the full intervention (including immediate ART for all individuals with HIV) were used to determine proportions of participants who knew their HIV status after the CHiP visit; proportions linking to care and initiating ART following referral; and overall proportions of HIV-infected individuals who knew their status (first 90 target) and the proportion of these on ART (second 90 target), pre- and post-intervention. We are not able to assess progress towards the third 90 target at this stage of the study. Overall, 121,130 adults (59,283 men and 61,847 women) were enumerated in 46,714 households during the first annual round (December 2013 to June 2015). Of the 45,399 (77%) men and 55,703 (90%) women consenting to the intervention, 80% of men and 85% of women knew their HIV status after the CHiP visit. Of 6,197 HIV-positive adults referred by CHiPs, 42% (95% CI: 40%-43%) initiated ART within 6 mo and 53% (95% CI: 52%-55%) within 12 mo. In the entire population, the estimated proportion of HIV-positive adults who knew their status increased from 52% to 78% for men and from 56% to 87% for women. The estimated proportion of known HIV-positive individuals on ART increased overall from 54% after the CHiP visit to 74% by the end of the round for men and from 53% to 73% for women. The estimated overall proportion of HIV-positive adults on ART, irrespective of whether they knew their status, increased from 44% to 61%, compared with the 81% target (the product of the first two 90 targets). Coverage was lower among young men and women than in older age groups. The main limitation of the study was the need for assumptions concerning knowledge of HIV status and ART coverage among adults not consenting to the intervention or HIV testing, although our conclusions were robust in sensitivity analyses.Conclusions: In this analysis, acceptance of HIV testing among those consenting to the intervention was high, although linkage to care and ART initiation took longer than expected. Knowledge of HIV-positive status increased steeply after 1 y, almost attaining the first 90 target in women and approaching it in men. The second 90 target was more challenging, with approximately three-quarters of known HIV-positive individuals on ART by the end of the annual round. Achieving higher test uptake in men and more rapid linkage to care will be key objectives during the second annual round of the intervention.Trial Registration: ClinicalTrials.gov NCT01900977. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]