PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial.
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SUBMITTER: Pickles M
PROVIDER: S-EPMC8478209 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
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PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial.
Pickles Michael M Cori Anne A Probert William J M WJM Sauter Rafael R Hinch Robert R Fidler Sarah S Ayles Helen H Bock Peter P Donnell Deborah D Wilson Ethan E Piwowar-Manning Estelle E Floyd Sian S Hayes Richard J RJ Fraser Christophe C
PLoS computational biology 20210902 9
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. ...[more]
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Project description:IntroductionUniversal 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.MethodsHPTN 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.ResultsOverall 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.ConclusionsUsing 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 numberClinicalTrials.gov number, NCT01900977, HPTN 071 [PopArt].
| S-EPMC10465013 | biostudies-literature
Project description:BackgroundA universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent.MethodsIn the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months.ResultsThe population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B.ConclusionsA combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.).
| S-EPMC6587177 | biostudies-literature
Project description:To determine the uptake of home-based HIV counselling and testing (HCT) in four HPTN 071 (PopART) trial communities (implementing a 'full' combination HIV prevention package that includes universal HIV testing and treatment) in Zambia. We also explore factors associated with uptake of HCT in these communities.HPTN 071 (PopART) is a three-arm community-randomized trial in 12 communities in Zambia and nine communities in South Africa evaluating the impact of a combination HIV prevention package, including universal HIV testing and treatment, on HIV incidence.Using a door-to-door approach that includes systematically revisiting households, individuals were offered participation in the intervention, and verbal consent was obtained. Data were analysed for the first 18 months of the intervention, December 2013 to June 2015 for individuals 18 years and older.Among 121?130 enumerated household members, 101?102 (83.5%) accepted the intervention. HCT uptake was 72.2% (66?894/92?612), similar by sex but varied across communities. HCT uptake was associated with younger age, sex, community, being symptomatic for TB and sexually transmitted infections and longer time since previous HIV test. Knowledge of HIV status due to the intervention increased by 36% overall and by 66% among HIV positive participants; the highest impact was among 18-24 years old.Overall acceptance of HIV-testing through offering a door-to-door-based combination HIV prevention package was 72.2%. The intervention increased knowledge of HIV status from ?50 to ?90%. However, challenges still remain and a one-off intervention is unlikely to be successful but will require repeated visits and multiple strategies.
| S-EPMC5491236 | biostudies-other
Project description:IntroductionHPTN 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.MethodsEnrollment 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.ResultsThe analysis based on community-level incidence shows a 25% reduction in incidence for Arm B communities compared to standard of care (RR: 0.75, 95% CI: 0.56-1.02, p = 0.06) while Arm A communities show no difference in HIV incidence compared to standard of care (RR: 1.08, 95% CI: 0.81-1.46, p = 0.56).ConclusionsOur re-analysis shows 25% reduction in HIV incidence comparing Arm B to Arm C communities. No effect was observed comparing Arm A communities to Arm C communities. These results align with the primary results of the PopART trial.Clinicaltrialsgov number, NCT01900977, HPTN 071 [PopArt].
| S-EPMC11887120 | biostudies-literature
Project description:BackgroundThe long-term impact of universal home-based testing and treatment as part of universal testing and treatment (UTT) on HIV incidence is unknown. We made projections using a detailed individual-based model of the effect of the intervention delivered in the HPTN 071 (PopART) cluster-randomised trial.MethodsIn this modelling study, we fitted an individual-based model to the HIV epidemic and HIV care cascade in 21 high prevalence communities in Zambia and South Africa that were part of the PopART cluster-randomised trial (intervention period Nov 1, 2013, to Dec 31, 2017). The model represents coverage of home-based testing and counselling by age and sex, delivered as part of the trial, antiretroviral therapy (ART) uptake, and any changes in national guidelines on ART eligibility. In PopART, communities were randomly assigned to one of three arms: arm A received the full PopART intervention for all individuals who tested positive for HIV, arm B received the intervention with ART provided in accordance with national guidelines, and arm C received standard of care. We fitted the model to trial data twice using Approximate Bayesian Computation, once before data unblinding and then again after data unblinding. We compared projections of intervention impact with observed effects, and for four different scenarios of UTT up to Jan 1, 2030 in the study communities.FindingsCompared with standard of care, a 51% (95% credible interval 40-60) reduction in HIV incidence is projected if the trial intervention (arms A and B combined) is continued from 2020 to 2030, over and above a declining trend in HIV incidence under standard of care.InterpretationA widespread and continued commitment to UTT via home-based testing and counselling can have a substantial effect on HIV incidence in high prevalence communities.FundingNational Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health.
| S-EPMC9646978 | biostudies-literature
Project description: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) and 4,396 non-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 <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments.
| S-EPMC8682874 | biostudies-literature
Project description:IntroductionUniversal HIV testing and treatment (UTT) has individual and public health benefits. HPTN 071 (PopART), a community-randomized trial in Zambia and South Africa, demonstrated that UTT decreased HIV incidence. This endpoint was assessed in a cohort of >48,000 randomly selected adults in the study communities. We evaluated the impact of UTT on HIV drug resistance in this cohort and compared other resistance-related outcomes in participants with recent versus non-recent HIV infection.MethodsTwo years after the start of HPTN 071 (2016-2017), 6259 participants were HIV positive and 1902 were viremic (viral load >400 copies/ml). HIV genotyping and antiretroviral (ARV) drug testing were performed for viremic participants in three groups: seroconverters (infected <1 year), non-seroconverters (infected >1 year, random subset) and participants with unknown duration of infection (random subset). A two-stage cluster-based approach was used to assess the impact of the study intervention on drug resistance. Treatment failure was defined as being viremic with ARV drugs detected. Participants were classified as ARV naïve based on self-report and ARV drug testing.ResultsGenotyping results were obtained for 758 participants (143 seroconverters; 534 non-seroconverters; and 81 unknown duration of infection). The estimated prevalence of resistance in the study communities was 37% for all viremic persons and 11% for all HIV-positive persons. There was no association between UTT and drug resistance. Resistance was detected in 14.0% of seroconverters and 40.8% of non-seroconverters (non-nucleoside reverse transcriptase inhibitor resistance: 14.0% and 39.9%; nucleoside/nucleotide reverse transcriptase inhibitor resistance: 0.7% and 15.5%; protease inhibitor resistance: 0% and 1.9%; multi-class resistance: 0.7% and 16.1%, respectively). ARV drugs were detected in 2/139 (1.4%) of seroconverters and 94/534 (17.6%) of non-seroconverters tested. These participants were classified as failing ART; 88 (93.6%) of the non-seroconverters failing ART had resistance. Mutations used for surveillance of transmitted drug resistance were detected in 10.5% of seroconverters and 15.1% of non-seroconverters who were ARV naive.ConclusionsUTT was not associated with an increase in drug resistance in this cohort. Higher rates of drug resistance and multi-class resistance were observed in non-seroconverters compared to seroconverters.
| S-EPMC9248006 | biostudies-literature
Project description:BackgroundAntiretroviral 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.MethodsStudy 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.ResultsAntiretroviral 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).ConclusionsAt 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.
| S-EPMC9697607 | biostudies-literature
Project description:PurposeThe PopART for Youth (P-ART-Y) study was nested within the HPTN 071 (PopART) trial, a three-arm community randomized trial in 21 communities in Zambia and South Africa. The P-ART-Y study evaluated the acceptability and uptake of a combination HIV prevention package among young people. We report on the HIV care cascade for adolescents aged 10-19 years from 14 communities receiving the full HIV prevention package in Zambia and South Africa.MethodsAdolescents were offered participation in the PopART intervention, which included universal home-based HIV testing, linkage to care, antiretroviral therapy (ART) adherence, and other services. Data were collected from September 2016 to December 2017, covering the third round (R3) of the intervention.ResultsWe enumerated (listed) 128,241 adolescents (Zambia: 95,295 and South Africa: 32,946). Of the adolescents offered HIV testing, 81.9% accepted in Zambia and 70.3% in South Africa. Knowledge of HIV status was higher among older adolescents and increased from 31.4% before R3 to 88.3% at the end of R3 in Zambia and from 28.3% to 79.5% in South Africa. Overall, there were 1,710 (1.9%) adolescents identified as living with HIV by the end of R3 (515 new diagnoses and 1,195 self-reported). Of the new diagnoses, 335 (65.0%) were girls aged 15-19 years. The median time to initiate ART was 5 months. ART coverage before and after R3 increased from 61.3% to 78.7% in Zambia and from 65.6% to 87.8% in South Africa, with boys having higher uptake than girls in both countries.ConclusionsThe PopART intervention substantially increased coverage toward the first and second UNAIDS 90-90-90 targets in adolescents.
| S-EPMC8022105 | biostudies-literature
Project description:INTRODUCTION:The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS:HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS:HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS:This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates.
| S-EPMC7028526 | biostudies-literature