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Abstract Introduction Adolescent girls and young women (AGYW) account for two‐thirds of new HIV infections in Africa. African AGYW have had high uptake of oral HIV pre‐exposure prophylaxis (PrEP) but low adherence, which might be improved by point‐of‐care adherence monitoring with tailored counselling. Methods From August 2022 to July 2023, we conducted a PrEP demonstration project with sexually active AGYW ages 16−30 years from 20 sites in South Africa, Eswatini, Kenya, Malawi, Uganda and Zambia. Participants were offered oral tenofovir‐based PrEP at enrolment and followed up at 1, 3 and 6 months. PrEP adherence was assessed by a point‐of‐care qualitative lateral flow urine tenofovir (TFV) assay indicating PrEP use in the prior 4 days, which accompanied real‐time adherence counselling that incorporated urine TFV results when testing was available (70.8% of month 1, 35.3% of month 3 and 83.9% of month 6 visits). We estimated overall adherence, correcting for missing test results, and analysed the association of having received urine TFV results at month 1 or 3 with subsequent urine TFV test positivity, using modified Poisson regression. Results Of the 3087 AGYW enrolled, the median age was 24 years (interquartile range 21−27), 75.7% were from South Africa, 2878 (93.2%) initiated PrEP at enrolment and 107 (3.5%) after enrolment. Visit retention was 92.0−96.2% for months 1, 3 and 6, and 2518 (90.1%) exited the study with a PrEP refill. Adherence, based on the point‐of‐care urine tenofovir test positivity rate, was estimated as 72%, 71% and 65% at months 1, 3 and 6, respectively. Women who received one prior urine TFV test had a 42% higher likelihood of a subsequent positive urine TFV test (adjusted odds ratio, OR = 1.42, 95% confidence interval, CI 1.27−1.60), and those having received two prior tests had a 67% higher likelihood (adjusted OR = 1.67; 95% CI 1.41−1.98). Observed HIV incidence was 1.38/100 person‐years (95% CI 0.97−2.08). Conclusions Oral PrEP uptake, recent adherence and persistence were high in a multisite cohort of young African women over 6 months of follow‐up. The use of a novel point‐of‐care tenofovir assay with tailored real‐time adherence counselling was associated with increased adherence to PrEP at subsequent visits, warranting further study. Clinical trials registration clinicaltrials.gov NCT05746065

Abstract People 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

BackgroundOral pre-exposure prophylaxis (PrEP) using co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) is a potent HIV prevention method for men and women, with its efficacy highly dependent on adherence. A pivotal HIV efficacy study combined with a directly observed pharmacological study defined the thresholds for HIV protection in men who have sex with men (MSM), which are the keys to PrEP promotion and development of new PrEP agents. For African women at risk for HIV and belonging to a priority group considered due to disproportionately high incident HIV infections, the variable adherence in PrEP clinical trials and the limited pharmacologic data have resulted in a lack of clarity about the PrEP adherence required for HIV protection. We propose a study to quantify the adherence–concentration–efficacy thresholds of TDF/FTC PrEP among African cisgender women to inform decisions about optimal PrEP dosing and adherence for HIV protection.MethodsWe randomized 45 low-risk HIV-uninfected African women, aged 18–30 years old, to directly observe the TDF/FTC PrEP of two, four, or seven doses per week for 8 weeks. A complementary age-matched pregnant women cohort at high risk of HIV, who will receive seven doses per week, was recruited (N = 15) with the primary aim of establishing benchmark concentrations in dried blood spots and peripheral blood mononuclear cells. Plasma, whole blood (WB), urine, hair, vaginal fluid, and vaginal tissue (non-pregnant women only) were archived for future testing. Drug concentrations were measured using methods validated for each biological matrix. Pharmacokinetic models were fitted to drug concentrations to quantify concentration–adherence thresholds. To define the drug concentrations associated with HIV protection, we applied the newly defined thresholds from the primary pharmacologic trial to the subset of women randomized to TDF/FTC or TDF in the Partners PrEP Study with the drug concentration assessed in plasma and WB samples. Multiple imputation was used to construct a data set with drug concentrations at each visit when an HIV test was performed for the entire cohort, replicating the work for MSM.DiscussionThe proposed study generated the first African women-specific TDF–PrEP adherence–concentration–efficacy thresholds essential for guiding the accurate interpretation of TDF/FTC PrEP programs and clinical trials of novel HIV prevention products using TDF/FTC as an active control. Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT05057858).

Abstract Broadly neutralizing monoclonal antibodies (mAbs) are being developed for HIV-1 prevention. Hence, these mAbs and licensed oral pre-exposure prophylaxis (PrEP) (tenofovir-emtricitabine) can be concomitantly administered in clinical trials. In 48 US participants (men and transgender persons who have sex with men) who received the HIV-1 mAb VRC01 and remained HIV-free in an antibody-mediated-prevention trial (ClinicalTrials.gov #NCT02716675), we conduct a post-hoc analysis and find that VRC01 clearance is 0.08 L/day faster (p = 0.005), and dose-normalized area-under-the-curve of VRC01 serum concentration over-time is 0.29 day/mL lower (p

Abstract Introduction The global incidence of sexually transmitted infections (STIs) has been rapidly increasing over the past decade, with more than one million curable STIs being acquired daily. Young women in sub-Saharan Africa have a high prevalence and incidence of both curable STIs and HIV. The use of doxycycline as a prophylaxis to prevent STIs is promising; however, clinical trials, to date, have only been conducted among men who have sex with men (MSM) in high-income settings. We describe the characteristics of participants enrolled in the first trial to determine the efficacy of doxycycline post-exposure prophylaxis (PEP) to reduce STI incidence among women taking daily, oral HIV pre-exposure prophylaxis (PrEP). Methods This is an open-label 1:1 randomized clinical trial on the efficacy of doxycycline PEP compared with standard of care (e.g., quarterly STI screening and treatment) to reduce incident bacterial STIs – Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum – among Kenyan women aged ≥18 and ≤30 years. All were also taking HIV pre-exposure prophylaxis (PrEP). We describe the baseline characteristics, STI prevalence, and STI risk perception of participants. Results Between February 2020 and November 2021, 449 women were enrolled. The median age was 24 years (IQR 21–27), the majority were never married (66.1%), 370 women (82.4%) reported having a primary sex partner, and 33% had sex with new partners in the three months prior to enrolment. Two-thirds (67.5%, 268 women) did not use condoms, 36.7% reported transactional sex, and 43.2% suspected their male partners of having sex with other women. Slightly less than half (45.9%, 206 women) were recently concerned about being exposed to an STI. The prevalence of STIs was 17.9%, with C. trachomatis accounting for the majority of infections. Perceived risk of STIs was not associated with the detection of an STI. Conclusion Young cisgender women using HIV PrEP in Kenya and enrolled in a trial of doxycycline postexposure prophylaxis had a high prevalence of curable STIs and represent a target population for an STI prevention intervention.

Abstract Introduction In 2021, there were 38.4 million people living with HIV (PLHIV) globally, of which 20.6 million (54%) were living in Eastern and Southern Africa. Longitudinal studies, inclusive of community randomized trials (CRTs), provide critical evidence to guide a broad range of health care interventions including HIV prevention. In this study, we have used an individual-level cohort study design to evaluate the association between sex and other baseline characteristics and participant retention in the HPTN 071 (PopART) trial in Zambia and South Africa. Methods HPTN 071 (PopART) was a community randomized trial (CRT) conducted from 2013 to 2018, in 21 communities. The primary outcome was measured in a randomly selected population cohort (PC), followed up over 3 to 4 years at annual rounds. PC retention was defined as completion of an annual follow-up questionnaire. Baseline characteristics were described by study arm and Poisson regression analyses used to measure the association between baseline factors and retention. In addition, we present a description of researcher-documented reasons for study withdrawal by PC participants. Results Of the 38,474 participants enrolled during the first round of the trial (PC0), most were women (27,139, 71%) and 73% completed at least one follow-up visit. Retention was lower in men (adj RR: 0.90; 95% CI: 0.88, 0.91) and higher among older participants (adj RR: 1.23; 95% CI 1.20, 1.26) when comparing ages 35–44 to 18–24 years. Retention was higher among individuals with high socioeconomic status (SES) (adj RR 1.16; 95% CI 1.14, 1.19) and medium SES (adj RR 1.12; 95% CI 1.09, 1.14) compared to low SES. The most common reasons for study withdrawal were study refusal (23%) and relocation outside the CRT catchment area (66%). Conclusion Despite challenges, satisfactory retention outcomes were achieved in PopART with limited variability across study arms. In keeping with other studies, younger age, male sex, and lower SES were associated with lower levels of retention. Relocation outside of catchment area was the most common reason for non-retention in this CRT.

Abstract Background Trust is an important cornerstone of patient-provider communication. Accurate reporting of pre-exposure prophylaxis (PrEP) adherence is vital for providers to determine who needs adherence support, especially adolescent girls and young women (AGYW) disproportionately affected by newly diagnosed HIV. Methods This is a secondary analysis of the HPTN 082 open-label PrEP demonstration trial. From 2016–2018, 451 AGYW aged 16–25 years were enrolled in South Africa (Cape Town and Johannesburg) and Zimbabwe (Harare). PrEP was initiated by 427, and 354 (83%) had month three patient-reported adherence responses and intracellular tenofovir diphosphate (TFV-DP) measurements. The patient-reported adherence response to ‘In the past month, how often did you take the tablet?’ was dichotomized as ‘high’ if the response was every day or most days, and ‘low’ if some days or not many days or never. The biomarker marker evidence of adherence in dried blood spots was defined as ‘high’ if TFV-DP ≥ 700, and ‘low’ if

Abstract Introduction HIV controllers have low viral loads (VL) without antiretroviral treatment (ART). We evaluated viraemic control in a community‐randomized trial conducted in Zambia and South Africa that evaluated the impact of a combination prevention intervention on HIV incidence (HPTN 071 [PopART]; 2013–2018). Methods VL and antiretroviral (ARV) drug testing were performed using plasma samples collected 2 years after enrolment for 4072 participants who were HIV positive at the start of the study intervention. ARV drug use was assessed using a qualitative laboratory assay that detects 22 ARV drugs in five drug classes. Participants were classified as non‐controllers if they had a VL ≥2000 copies/ml with no ARV drugs detected at this visit. Additional VL and ARV drug testing was performed at a second annual study visit to confirm controller status. Participants were classified as controllers if they had VLs male, p = 0.027). There was no significant association between controller status and age, study country or herpes simplex virus type 2 (HSV‐2) status at study enrolment. Conclusions To our knowledge, this report presents the first large‐scale, population‐level study evaluating the prevalence of viraemic control and associated factors in Africa. A key advantage of this study was that a biomedical assessment was used to assess ARV drug use (vs. self‐reported data). This study identified a large cohort of HIV controllers and non‐controllers not taking ARV drugs, providing a unique repository of longitudinal samples for additional research. This cohort may be useful for further studies investigating the mechanisms of virologic control.

Abstract Introduction Secondary distribution of HIV self‐tests (HIVST) by HIV‐negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV). Methods We conducted an open‐label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard‐of‐care (SOC; invitation letter to male partner for fast‐track testing). Women were followed until 12 months post‐partum. Male partners were offered confirmatory HIV testing and facilitated linkage to antiretroviral treatment (ART) or oral pre‐exposure prophylaxis (PrEP). Using intention‐to‐treat analysis, primary outcomes were male partner testing at the clinic and initiation on PrEP or ART evaluated through 12 months post‐partum (ClinicalTrials.gov, NCT03484533). Results From November 2018 to March 2020, 500 PWLHIV were enrolled with a median age of 27 years (interquartile range [IQR] 23–30); 332 were randomized to HIVST and 168 to SOC with 437 PWLHIV (87.4%) completing 12 months follow‐up post‐partum. Of 236 male partners who tested at the clinic and enrolled (47.2%), their median age was 31 years (IQR 27–36), 45 (88.3%) men with HIV started ART and 113 (61.1%) HIV‐negative men started PrEP. There was no intervention effect on male partner testing (hazard ratio [HR] 1.04; 95% confidence interval [CI]: 0.79–1.37) or time to ART or PrEP initiation (HR 0.96; 95% CI: 0.69–1.33). Two male partners and two infants acquired HIV for an incidence of 0.99 per 100 person‐years (95% CI: 0.12–3.58) and 1.46 per 100 person‐years (95% CI: 0.18%–5.28%), respectively. Social harms related to study participation were experienced by six women (HIVST = 5, SOC = 1). Conclusions Almost half of the partners of Ugandan PWLHIV tested for HIV with similar HIV testing rates and linkage to ART or PrEP among the secondary distribution of HIVST and SOC arms. Although half of men became aware of their HIV serostatus and linked to services, additional strategies to reach male partners of women in antenatal care are needed to increase HIV testing and linkage to services among men.

Abstract Introduction Universal HIV testing and treatment aims to identify all people living with HIV and offer them treatment, decreasing the number of individuals with unsuppressed HIV and thus reducing HIV transmission. Longitudinal follow‐up of individuals with and without HIV in a cluster‐randomized trial of communities allowed for the examination of community‐ and individual‐level measures of HIV risk and HIV incidence. Methods HPTN 071 (PopART) was a three‐arm cluster‐randomized trial conducted between 2013 and 2018 that evaluated the use of two combination HIV prevention strategies implemented at the community level to reduce HIV incidence compared to the standard of care. The trial, conducted in 21 communities in Zambia and South Africa, measured HIV incidence over 36 months in a population cohort of ∼2000 randomly selected adults per community aged 18–44. Multilevel models were used to assess the association between HIV incidence and community‐ and individual‐level socio‐demographic and behavioural risk factors, as well as prevalence of detectable virus (PDV) defined as the estimated proportion of the community with unsuppressed viral load. Results Overall HIV incidence was 1.49/100 person‐years. Communities with less financial wealth and communities with more individuals reporting having sex partners outside of the community or two or more sexual partners had higher HIV incidence. PDV at 2 years of study was 6.8% and was strongly associated with HIV incidence: for every 50% relative reduction in community PDV, there was a 49% (95% confidence interval [CI]: 37%–58%, p < 0.001) relative decrease in HIV incidence. At the individual level; socio‐economic status, AUDIT score, medical male circumcision and certain sexual behaviours were associated with HIV risk. Conclusions Using data from the PopART randomized trial, we found several associations of HIV incidence with community‐level measures reflecting the sexual behaviour and socio‐economic make‐up of each community. We also found a strong association between community PDV and HIV incidence supporting the use of PDV as a tool for monitoring progress in controlling the epidemic. Lastly, we found significant individual‐level factors of HIV risk that are generally consistent with previous HIV epidemiological research. These results have the potential to identify high high‐incidence communities, inform structural‐level interventions, and optimize individual‐level interventions for HIV prevention. Clinical Trial Number ClinicalTrials.gov number, NCT01900977, HPTN 071 [PopArt]

Abstract Introduction African adolescent girls and young women (AGYW) have high rates of HIV acquisition and are a priority population for HIV pre‐exposure prophylaxis (PrEP). PrEP implementation has been limited by AGYW's low perceived HIV risk and provider demands. A decision support tool (DST) with information about PrEP could improve clients’ risk perception, knowledge about PrEP, informed decision‐making and motivation to use PrEP based on their risk, facilitating PrEP delivery in primary healthcare (PHC) clinics. Methods We designed MyPrEP, a client‐facing DST about PrEP and HIV prevention, with youth‐friendly information and images. The impact of the MyPrEP tool was assessed among HIV‐negative women aged 18–25 years presenting to a PHC clinic in Johannesburg, South Africa from March 2019 to 2020. AGYW were randomized by day to the DST or a general health website as the control condition. A clinician blinded to DST versus control allocation provided standard of care counselling about PrEP, offered PrEP, administered a questionnaire and conducted sexually transmitted infection testing. The primary outcome was PrEP initiation and the secondary outcome was PrEP persistence at 1 month, determined by pharmacy dispensation records. Results Of 386 AGYW screened, 353 were randomized (DST n = 172, control n = 181) with a median age of 21 years (interquartile range [IQR] 20, 23) and 56% (199/353) attending the clinic for HIV testing, 46% (164/353) using contraception, 15% (53/353) using condoms consistently and 37% (108/353) with a curable sexually transmitted infection. PrEP was initiated by 97% in the DST group and 94% in the control group (OR 1.79; 95% confidence interval, CI = 0.79–1.53), of whom two‐thirds planned to continue PrEP until they decided if they liked PrEP. At 1 month, PrEP persistence was 19% in the DST and 10% in the control group (OR 1.97, 95% CI 1.08–3.69). Ninety‐nine percent randomized to the DST reported satisfaction with MyPrEP. Conclusions Among AGYW attending a South African PHC clinic, PrEP uptake was >90% with two‐fold higher PrEP persistence at 1 month in those randomized to use the MyPrEP DST. Given the need for strategies to support PrEP implementation and improve low PrEP persistence among African AGYW, a PrEP DST warrants further evaluation.

Abstract Introduction Multiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo‐ to active‐controlled designs; however, active‐controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information. Methods We compared the active‐controlled study (HPTN 084) of injectable cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person‐years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB‐LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo‐controlled trials, adjusted for observed adherence to daily pills. Results Distribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB‐LA versus placebo in all three settings showed a consistent risk reduction of 93%–94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%–56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%–40% for this level of daily pill use. Conclusions Counterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo‐based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders.

Abstract Background Women in Africa face disproportionate risk of human immunodeficiency virus (HIV) acquisition, accounting for more than half of new infections in Africa and similarly face a disproportionate burden of sexually transmitted infections (STIs). Very high STI prevalence is being observed globally, especially among people taking pre-exposure prophylaxis (PrEP) for HIV prevention. Doxycycline post-exposure prophylaxis (dPEP) has been proposed as an STI prevention strategy to reduce chlamydia, syphilis, and possibly gonorrhea, and trials are ongoing among cisgender men who have sex with men (MSM) and transgender women who are taking PrEP in high-income settings. We designed and describe here the first open-label trial to determine the effectiveness of dPEP to reduce STI incidence among cisgender women. Methods We are conducting an open-label 1:1 randomized trial of dPEP versus standard of care (STI screening and treatment and risk-reduction counseling without dPEP) among 446 Kenyan women aged ≥ 18 and ≤ 30 years old women taking PrEP. Women are followed for 12 months, with quarterly STI testing, treatment, and adherence counseling. The primary trial outcome will be the combined incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, compared between the randomized groups. We will also assess dPEP acceptability, tolerability, safety, impact on sexual behavior, adherence, and occurrence of antimicrobial resistance (AMR) in N. gonorrhoeae and C. trachomatis isolates. Finally, we will estimate cost per incident STI case and complications averted accounting for nonadherence and benefits relative AMR or side effects. Discussion The results of this trial may have immediate implications for the global epidemic of STIs and sexual health. If effective, dPEP could put STI prevention into women’s hands. While dPEP may be able to prevent STIs, it carries important risks that could counter its benefits; global debate about the balance of these potential risks and benefits requires data to inform policy and implementation and our study aims to fill this gap. Trial registration ClinicalTrials.gov NCT04050540 .

Abstract Background HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule. Methods We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15–20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models. Discussion This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery. Trial registration ClinicalTrials.gov NCT03675256 . Registered on September 18, 2018

Summary: Background: Global scale-up of HIV pre-exposure prophylaxis (PrEP) includes services to HIV-negative people in partnerships with people living with HIV (serodifferent couples). Data are needed on HIV outcomes, including uptake and adherence to PrEP and antiretroviral treatment (ART), to describe the impact of integrating PrEP into an existing HIV program. Methods: Using a stepped-wedge cluster randomized trial design, we launched PrEP delivery for HIV-negative members of serodifferent couples in Uganda by integrating PrEP into existing ART programs for people living with HIV. The program provided PrEP training for ART providers, ongoing technical assistance, and a provisional supply chain mechanism for PrEP medication. Primary data on PrEP initiation, PrEP refills, ART initiation, and HIV viremia at 6 months (measured at 42-270 days) were collected through data abstraction of medical records from HIV-serodifferent couples sequentially enrolling at the ART clinics. Modified Poisson regression models, controlling for time and cluster, compared viral suppression (

Abstract Trial results for two COVID-19 vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS). It remains unknown whether this efficacy is mediated by lowering SARS-CoV-2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP). We aim to assess and compare the population impact of vaccines with different efficacy profiles (VESYMP and VESUSC) satisfying licensure criteria. We developed a mathematical model of SARS-CoV-2 transmission, calibrated to data from King County, Washington. Rollout scenarios starting December 2020 were simulated with combinations of VESUSC and VESYMP resulting in up to 100% VEDIS. We assumed no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported. Rollouts of 1 M vaccinations (5000 daily) using vaccines with 50% VEDIS are projected to prevent 23–46% of infections and 31–46% of deaths over 1 year. In comparison, vaccines with 90% VEDIS are projected to prevent 37–64% of infections and 46–64% of deaths over 1 year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a “symptom reducing” vaccine will require twice as many people vaccinated than a “susceptibility reducing” vaccine with the same 90% VEDIS to prevent 50% of the infections and death over 1 year. Delaying the start of the vaccination by 3 months decreases the expected population impact by more than 50%. Vaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

Abstract Background In a cluster-randomised trial (CRT) of combination HIV prevention (HPTN 071 (PopART)) in 12 Zambian communities and nine South African communities, carried out from 2012 to 2018, the intervention arm A that offered HIV treatment irrespective of CD4 count did not have a significant impact on population level HIV incidence. Intervention arm B, where HIV incidence was reduced by 30%, followed national guidelines that mid trial (2016) changed from starting HIV treatment according to a CD4 threshold of 500 to universal treatment. Using social science data on the 21 communities, we consider how place (community context) might have influenced the primary outcome result. Methods A social science component documented longitudinally the context of trial communities. Data were collected through rapid qualitative assessment, interviews, group discussions and observations. There were a total of 1547 participants and 1127 observations. Using these data, literature and a series of qualitative analysis steps, we identified key community characteristics of relevance to HIV and triangulated these with HIV community level incidence. Results Two interdependent social factors were relevant to communities’ capability to manage HIV: stability/instability and responsiveness/resistance. Key components of stability were social cohesion; limited social change; a vibrant local economy; better health, education and recreational services; strong institutional presence; established middle-class residents; predictable mobility; and less poverty and crime. Key components of responsiveness were community leadership being open to change, stronger history of HIV initiatives, willingness to take up HIV services, less HIV-related stigma and a supported and enterprising youth population. There was a clear pattern of social factors across arms. Intervention arm A communities were notably more resistant and unstable. Intervention arm B communities were overall more responsive and stable. Conclusions In the specific case of the dissonant primary outcome results from the HPTN 071 (PopART) trial, the chance allocation of less stable, less responsive communities to arm A compared to arm B may explain some of the apparently smaller impact of the intervention in arm A. Stability and responsiveness appear to be two key social factors that may be relevant to secular trends in HIV incidence. We advocate for a systematic approach, using these factors as a framework, to community context in CRTs and monitoring HIV prevention efforts. Trial registration ClinicalTrials.gov NCT01900977 . Registered on July 17, 2013.

IntroductionSouth Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition.MethodsDuring December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16-35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12-18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection.Results5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05-5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV.ConclusionsHIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population.Clinical trial registrationClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites.

Introduction Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy and is recommended for populations at risk of HIV, including adolescent girls and young women (AGYW) in HIV endemic settings. However, PrEP continuation and high adherence remain challenges to its impact. Existing PrEP adherence interventions can be time- and cost-intensive. Widescale PrEP delivery will require the identification of layered PrEP support strategies for AGYW with diverse prevention needs. We describe the design of a sequential multiple assignment randomized trial (SMART) to evaluate a PrEP adherence support model using scalable, stepped interventions in AGYW in South Africa. Methods “PrEP SMART” is a randomized trial in Johannesburg, South Africa, enrolling AGYW who are between 18 and 25 years of age, sexually active, newly initiating PrEP, and have regular access to a mobile phone. Participants are randomized 1:1 to standard-of-care PrEP counseling with either two-way SMS or WhatsApp group adherence support. Adherence is assessed at three months using tenofovir diphosphate (TFV-DP) levels from dried blood spots collected at month 2 to categorize participants as “responders” (TFV-DP ≥500 fmol/punch) or “non-responders” (TFV-DP Trial registration ClinicalTrials.gov, NCT04038060. Registered on 30 July 2019.

Summary: Background: Successful and sustainable models for HIV pre-exposure prophylaxis (PrEP) delivery in public health systems in Africa are needed. We aimed to evaluate the implementation of PrEP delivery integrated in public HIV care clinics in Kenya. Methods: As part of Kenya's national PrEP roll-out, we conducted a stepped-wedge cluster-randomised pragmatic trial to catalyse scale-up of PrEP delivery integrated in 25 public HIV care clinics. We selected high-volume clinics in these regions (ie, those with a high number of people living with HIV enrolled in HIV care and treatment). Clinics (each representing a cluster) were stratified by region and randomly assigned to the order in which clinic staff would receive PrEP training and ongoing technical support using numbered opaque balls picked from a bag. There was no masking. PrEP provision was done by clinic staff without additional financial support. Data were abstracted from records of individuals initiating PrEP. The primary outcome was the number of people initiating PrEP per clinic per month comparing intervention to control periods. Other outcomes included PrEP continuation, adherence, and incident HIV infections. This trial is registered with ClinicalTrials.gov, NCT03052010. Findings: After the baseline period, which started in January, 2017, every month two to six HIV care clinics crossed over from control to intervention, until August, 2017, when all clinics were implementing the intervention. Of 4898 individuals initiating PrEP (27 during the control period and 4871 during the intervention period), 2640 (54%) were women, the median age was 31 years (IQR 25–39), and 4092 (84%) reported having a partner living with HIV. The mean monthly number of PrEP initiations per clinic was 0·1 (SD 0·5) before the intervention and 7·5 (2·7) after intervention introduction (rate ratio 23·7, 95% CI 14·2–39·5, p

Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention.

Abstract Background The introduction of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus-1 (HIV-1) prevention in Africa presents new challenges for health systems that are already overburdened because PrEP delivery requires frequent clinic visits (generally every 3 months) for HIV-1 testing and PrEP refills. HIV-1 self-testing (HIVST) has the potential to improve the efficiency of PrEP delivery by decreasing the number of clinic visits. Here, we describe the rationale and design of a randomized, noninferiority trial designed to test the effectiveness and safety of using HIVST to support PrEP delivery in Kenya. Methods The JiPime-JiPrEP (Kiswahili for ‘Test Yourself, PrEP Yourself’) study is a three-arm randomized trial taking place in Thika, Kenya. Participants (n = 495) are eligible for enrollment if they are at least 18 years old, HIV-1 seronegative, and have been taking PrEP for 1 month. Three distinct participant types will be enrolled: men (n = 165) and women (n = 165) who are in mutually disclosed HIV-1 serodiscordant relationships, and women (n = 165) who are at HIV-1 risk and not in a known serodiscordant relationship. Participants in each of these subpopulations will be 1:1:1 randomized to: 1) the standard of care, with quarterly clinic visits; 2) oral HIVST, with biannual clinic visits plus oral HIVSTs to use at the quarters between those visits; or 3) blood-based HIVST, with biannual clinic visits plus blood-based HIVSTs. All participants will complete quantitative surveys and provide blood samples for the objective measurement of PrEP adherence at baseline, 6 months, and 12 months. The primary outcomes are PrEP adherence, PrEP continuation, and HIV-1 testing, measured at 6 months and secondarily at 12 months. Discussion The findings from this trial can help to understand how HIVST—a new HIV-1 testing technology—can support health systems in sub-Saharan Africa. Additionally, the findings can inform policy aimed at improving the efficiency of PrEP implementation and scale-up in Kenya. Trial registration ClinicalTrials.gov, NCT03593629. Retrospectively registered on 20 July 2018.

Summary: We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

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

Background: In cluster-randomized controlled trials (C-RCTs) of HIV prevention strategies, HIV incidence is expensive to measure directly. Surveillance data on HIV diagnoses or viral suppression could provide cheaper incidence estimates. We used mathematical modelling to evaluate whether these measures can replace HIV incidence measurement in C-RCTs. Methods: We used a US HIV transmission model to simulate C-RCTs of expanded antiretroviral therapy(ART), pre-exposure prophylaxis(PrEP) and HIV testing, together or alone. We tested whether modelled reductions in total new HIV diagnoses, diagnoses with acute infection, diagnoses with early infection(CD4 > 500 cells/μl), diagnoses adjusted for testing volume, or the proportion virally non-suppressed, reflected HIV incidence reductions. Results: Over a two-year trial expanding PrEP alone, modelled reductions in total diagnoses underestimated incidence reductions by a median six percentage points(pp), with acceptable variability(95 % credible interval -14,-2pp). For trials expanding HIV testing alone or alongside ART + PrEP, greater, highly variable bias was seen[-20pp(-128,-1) and -30pp(-134,-16), respectively]. Acceptable levels of bias were only seen over longer trial durations when levels of awareness of HIV-positive status were already high. Expanding ART alone, only acute and early diagnoses reductions reflected incidence reduction well, with some bias[-3pp(-6,-1) and -8pp(-16,-3), respectively]. Early and adjusted diagnoses also reliably reflected incidence when scaling up PrEP alone[bias -5pp(-11,1) and 10pp(3,18), respectively]. For trials expanding testing (alone or with ART + PrEP), bias for all measures explored was too variable for them to replace direct incidence measures, unless using diagnoses when HIV status awareness was already high. Conclusions: Surveillance measures based on HIV diagnoses may sometimes be adequate surrogates for HIV incidence reduction in C-RCTs expanding ART or PrEP only, if adjusted for bias. However, all surveillance measures explored failed to approximate HIV incidence reductions for C-RCTs expanding HIV testing, unless levels of awareness of HIV-positive status were already high.

Abstract Background Antiretroviral therapy (ART) for HIV-infected persons and pre-exposure prophylaxis (PrEP) for uninfected persons are extraordinarily effective strategies for HIV prevention. In Africa, the region which shoulders the highest HIV burden, HIV care is principally delivered through public health HIV care clinics, offering an existing platform to incorporate PrEP delivery and maximize ART and PrEP synergies. However, successfully bringing this integrated approach to scale requires an implementation science evaluation in public health settings. Methods The Partners Scale Up Project is a prospective, pragmatic implementation evaluation, designed as a stepped-wedge, cluster-randomized trial, operating at 24 clinics in Kenya. In collaboration with the Kenya Ministry of Health, we are catalyzing scaled implementation of PrEP delivery integrated in HIV care clinics. The intervention package includes staff training, clinic streamlined access to PrEP commodity from the Kenya Medical Supply Authority, and ongoing intensive technical assistance to rigorously assess how PrEP delivery is implemented. PrEP service delivery including retention efforts are conducted by the clinic staff with no additional resources from the project. Guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework and Consolidated Framework for Implementation Science Research, project progress and learning are documented through ongoing monitoring and process evaluations, including chart abstraction and individual and key informant interviews, to evaluate pragmatic rollout and understand barriers and facilitators for successful PrEP delivery in this setting. In this staged rollout design, each step provides data for both pre-implementation (baseline) and implementation periods, and we will compare time points across steps in the baseline versus implementation periods. Discussion Cost-effective delivery models are urgently needed to maximize the public health impact of PrEP and ART. The Partners Scale Up Project will set the stage for full-scale PrEP implementation fully run and owned by the Kenya Ministry of Health. The work combines nationally sponsored PrEP delivery with technical support and implementation science from academic partners, defining a new but sustainable paradigm for public health collaboration. Trial registration Registered with ClinicalTrials.gov on February 14, 2017:NCT03052010.

Background: In vitro, animal, biological and observational clinical studies suggest that some hormonal methods, particularly depot medroxyprogesterone acetate – DMPA, may increase women’s risk of HIV acquisition. DMPA is the most common contraceptive used in many countries worst affected by the HIV epidemic. To provide robust evidence for contraceptive decision-making among women, clinicians and planners, we are conducting the Evidence for Contraceptive Options and HIV Outcomes (ECHO) study in four countries with high HIV incidence and DMPA use: Kenya, South Africa, Swaziland, and Zambia (Clinical Trials.gov identifier NCT02550067). Study design: We randomized HIV negative, sexually active women 16-35 years old requesting effective contraception and agreeing to participate to either DMPA, the copper T 380A intrauterine device or levonorgestrel implant. Participants attend a contraception support visit after 1 month and quarterly visits thereafter for up to 18 months. Participants receive a standard HIV prevention package and contraceptive side-effect management at each visit. The primary outcome is HIV seroconversion. Secondary outcomes include pregnancy, serious adverse events and method discontinuation. The sample size of 7800 women provides 80% power to detect a 50% relative increase in HIV risk between any of the three method pairs, assuming 250 incident infections per comparison. Ethical considerations: Several WHO consultations have concluded that current evidence on HIV risk associated with DMPA is inconclusive and that a randomized trial is needed to guide policy, counselling and choice. Previous studies suggest that women without a specific contraceptive preference are willing to accept randomization to different contraceptive methods. Stringent performance standards are monitored by an independent data and safety monitoring board approximately every 6 months. The study has been conducted with extensive stakeholder engagement. Conclusions: The ECHO study is designed to provide robust evidence on the relative risks (HIV acquisition) and benefits (pregnancy prevention) between three effective contraceptive methods.

Background: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk. Demonstration projects conducted in diverse settings worldwide illustrate practical examples of how PrEP can be delivered. This manuscript presents estimates of effectiveness and patterns of PrEP use within a two-year demonstration project of PrEP for HIV-negative members of heterosexual HIV serodiscordant couples in East Africa. Methods: The PrEP delivery model integrated PrEP into HIV treatment services, prioritizing PrEP use for HIV-negative partners within serodiscordant couples before and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART). We measured PrEP uptake through pharmacy records and adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP. Ninety-seven percent of HIV-negative partners initiated PrEP. Objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected. Four incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p

Background: In vitro, animal, biological and observational clinical studies suggest that some hormonal methods, particularly depot medroxyprogesterone acetate – DMPA, may increase women’s risk of HIV acquisition. DMPA is the most common contraceptive used in many countries worst affected by the HIV epidemic. To provide robust evidence for contraceptive decision-making among women, clinicians and planners, we are conducting the Evidence for Contraceptive Options and HIV Outcomes (ECHO) study in four countries with high HIV incidence and DMPA use: Kenya, South Africa, Swaziland, and Zambia (Clinical Trials.gov identifier NCT02550067). Study design: We randomized HIV negative, sexually active women 16-35 years old requesting effective contraception and agreeing to participate to either DMPA, the copper T 380A intrauterine device or levonorgestrel implant. Participants attend a contraception support visit after 1 month and quarterly visits thereafter for 12 to 18 months. Participants receive a standard HIV prevention package and contraceptive side-effect management at each visit. The primary outcome is HIV seroconversion. Secondary outcomes include pregnancy, serious adverse events and method discontinuation. The sample size of 7800 women provides 80% power to detect a 50% difference in HIV risk between any of the three method pairs, assuming 250 incident infections per comparison. Ethical considerations: Several WHO consultations have concluded that current evidence on HIV risk associated with DMPA is inconclusive and that a randomized trial is needed to guide policy, counselling and choice. Previous studies suggest that women without a specific contraceptive preference are willing to accept randomization to different contraceptive methods. Stringent performance standards are monitored by an independent data and safety monitoring board approximately every 6 months. The study has been conducted with extensive stakeholder engagement. Conclusions: The ECHO study is designed to provide robust evidence on the relative risks (HIV acquisition) and benefits (pregnancy prevention) between three effective contraceptive methods.

Background: The life expectancy of HIV-positive individuals receiving antiretroviral therapy (ART) is approaching that of HIV-negative people. However, little is known about how these populations compare in terms of health-related quality of life (HRQoL). We aimed to compare HRQoL between HIV-positive and HIV-negative people in Zambia and South Africa. Methods: As part of the HPTN 071 (PopART) study, data from adults aged 18–44 years were gathered between Nov 28, 2013, and March 31, 2015, in large cross-sectional surveys of random samples of the general population in 21 communities in Zambia and South Africa. HRQoL data were collected with a standardised generic measure of health across five domains. We used β-distributed multivariable models to analyse differences in HRQoL scores between HIV-negative and HIV-positive individuals who were unaware of their status; aware, but not in HIV care; in HIV care, but who had not initiated ART; on ART for less than 5 years; and on ART for 5 years or more. We included controls for sociodemographic variables, herpes simplex virus type-2 status, and recreational drug use. Findings: We obtained data for 19 750 respondents in Zambia and 18 941 respondents in South Africa. Laboratory-confirmed HIV status was available for 19 330 respondents in Zambia and 18 004 respondents in South Africa; 4128 (21%) of these 19 330 respondents in Zambia and 4012 (22%) of 18 004 respondents in South Africa had laboratory-confirmed HIV. We obtained complete HRQoL information for 19 637 respondents in Zambia and 18 429 respondents in South Africa. HRQoL scores did not differ significantly between individuals who had initiated ART more than 5 years previously and HIV-negative individuals, neither in Zambia (change in mean score −0·002, 95% CI −0·01 to 0·001; p=0·219) nor in South Africa (0·000, −0·002 to 0·003; p=0·939). However, scores did differ between HIV-positive individuals who had initiated ART less than 5 years previously and HIV-negative individuals in Zambia (−0·006, 95% CI −0·008 to −0·003; p

Introduction: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV. Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered. Methods: We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa. The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART). We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP. Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected. A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p

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.