Suchergebnisse

AbstractIntroductionUniversal 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]

IntroductionSuccessful global treatment as prevention (TasP) requires identifying HIV‐positive individuals at high risk for transmitting HIV, and having impact via potential infections averted. This study estimated the frequency and predictors of numbers of HIV transmissions and bacterial sexually transmitted infection (STI) acquisition among sexually active HIV‐positive individuals in care from three representative global settings.MethodsHIV‐positive individuals (n=749), including heterosexual men, heterosexual women and men who have sex with men (MSM) in HIV care, were recruited from Chiang Mai (Thailand), Rio De Janeiro (Brazil) and Lusaka (Zambia). Participants were assessed on HIV and STI sexual transmission risk variables, psychosocial characteristics and bacterial STIs at enrolment and quarterly for 12 months (covering 15 months). Estimated numbers of HIV transmissions per person were calculated using reported numbers of partners and sex acts together with estimates of HIV transmissibility, accounting for ART treatment and condom use.ResultsAn estimated 3.81 (standard error, (SE)=0.63) HIV transmissions occurred for every 100 participants over the 15 months, which decreased over time. The highest rate was 19.50 (SE=1.68) for every 100 MSM in Brazil. In a multivariable model, country×risk group interactions emerged: in Brazil, MSM had 2.85 (95% CI=1.45, 4.25, p<0.0001) more estimated transmissions than heterosexual men and 3.37 (95% CI=2.01, 4.74, p<0.0001) more than heterosexual women over the 15 months. For MSM and heterosexual women, the combined 12‐month STI incidence rate for the sample was 22.4% (95% CI=18.1%, 27.3%; incidence deemed negligible in heterosexual men). In the multivariable model, MSM had 12.3 times greater odds (95% CI=4.44, 33.98) of acquiring an STI than women, but this was not significant in Brazil. Higher alcohol use on the Alcohol Use Disorders Identification Test (OR=1.04, 95% CI=1.01, 1.08) was also significantly associated with increased STI incidence. In bivariate models for both HIV transmissions and STI incidence, higher depressive symptoms were significant predictors.ConclusionsThese data help to estimate the potential number of HIV infections transmitted and bacterial STIs acquired over time in patients established in care, a group typically considered at lower transmission risk, and found substantial numbers of estimated HIV transmissions. These findings provide an approach for evaluating the impact (in phase 2 studies) and potentially cost‐effectiveness of global TasP efforts.

AbstractIntroductionCross‐sectional incidence testing is used to estimate population‐level HIV incidence and measure the impact of prevention interventions. There are limited data evaluating the accuracy of estimates in settings where antiretroviral therapy coverage and levels of viral suppression are high. Understanding cross‐sectional incidence estimates in these settings is important as viral suppression can lead to false recent test results. We compared the accuracy of multi‐assay algorithms (MAA) for incidence estimation to that observed in the community‐randomized HPTN 071 (PopART) trial, where the majority of participants with HIV infection were virally suppressed.MethodsHIV incidence was assessed during the second year of the study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016–2017). Incidence estimates from three MAAs were compared to the observed incidence between years 1 and 2 (MAA‐C: LAg‐Avidity <2.8 ODn + BioRad Avidity Index <95% + VL >400 copies/ml; LAg+VL MAA: LAg‐Avidity <1.5 ODn + VL >1000 copies/ml; Rapid+VL MAA: Asanté recent rapid result + VL >1000 copies/ml). The mean duration of recent infection (MDRI) used for the three MAAs was 248, 130 and 180 days, respectively.Results and discussionThe study consisted of: 15,845 HIV‐negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV‐positive participants at the 2‐year visit. Sixty four (29%) of the seroconverters and 3227 (72%) prevelant positive participants were virally supressed (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17–1.53). Estimates of incidence were similar to observed incidence for MAA‐C, 1.26% (95% CI: 1.02–1.51) and the LAg+VL MAA, 1.29 (95% CI: 0.97–1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69–1.15, p<0.01).ConclusionsMAA‐C and the LAg+VL MAA provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting that the MDRI recommended by the manufacturer is too long or the assay is not accurately detecting enough recent infections.

AbstractIntroductionHIV 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).MethodsVL 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 <2000 with no ARV drugs detected at both visits. Non‐controllers who had ARV drugs detected at either visit were excluded from the analysis to minimize potential confounders associated with ARV drug access and uptake.ResultsThe final cohort included 126 viraemic controllers and 766 non‐controllers who had no ARV drugs detected. The prevalence of controllers among the 4072 persons assessed was 3.1% (95% confidence interval [CI]: 2.6%, 3.6%). This should be considered a minimum estimate, since high rates of ARV drug use in the parent study limited the ability to identify controllers. Among the 892 participants in the final cohort, controller status was associated with biological sex (female > 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.ConclusionsTo 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.

AbstractIntroductionUniversal 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.

AbstractIntroductionThe 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.MethodsHIV 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.ResultsHIV 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.ConclusionsThis 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.