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Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

ABSTRACT: Background:Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels. Methods:The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence. Results:A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (? = 0.92; P < .001). Conclusions:There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention.

SUBMITTER: Bradley J

PROVIDER: S-EPMC6049005 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

Bradley John J Floyd Sian S Piwowar-Manning Estelle E Laeyendecker Oliver O Young Alicia A Bell-Mandla Nomtha N Bwalya Justin J Bock Peter P Fidler Sarah S Ayles Helen H Hayes Richard J RJ

The Journal of infectious diseases 20180701 3

<h4>Background</h4>Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels.<h4>Methods</h4>The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approxim ...[more]

PMID: 29659909

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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.).

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].

Project description:BackgroundComprehensive HIV prevention strategies have raised concerns that knowledge of interventions to reduce risk of HIV infection might mitigate an individual's perception of risk, resulting in riskier sexual behaviour. We investigated the prespecified secondary outcomes of the HPTN 071 (PopART) trial to determine whether a combination HIV prevention strategy, including universal HIV testing and treatment, changed sexual behaviour; specifically, we investigated whether there was evidence of sexual risk compensation.MethodsHPTN 071 (PopART) was a cluster-randomised trial conducted during 2013-18, in which we randomly assigned 21 communities with high HIV prevalence in Zambia and South Africa (total population, approximately 1 million) to combination prevention intervention with universal antiretroviral therapy (ART; arm A), prevention intervention with ART provided according to local guidelines (universal since 2016; arm B), or standard of care (arm C). The trial included a population cohort of approximately 2000 randomly selected adults (aged 18-44 years) in each community (N=38 474 at baseline) who were followed up for 36 months. A prespecified secondary objective was to evaluate the impact of the PopART intervention compared with standard of care on herpes simplex virus type 2 (HSV-2) and sexual behaviour (N=20 422 completed final visit). Secondary endpoints included differences in sexual risk behaviour measures at 36 months and were assessed using a two-stage method for matched cluster-randomised trials. This trial is registered with ClinicalTrials. gov, number NCT01900977.FindingsThe PopART intervention did not substantially change probability of self-reported multiple sex partners, sexual debut, or pregnancy in women at 36 months. Adjusted for baseline community prevalence, reported condomless sex was significantly lower in arm A versus arm C (adjusted prevalence ratio 0·80 [95% CI 0·64-0·99]; p=0·04) but not in arm B versus arm C (0·94 [0·76-1·17]; p=0·55). 3-year HSV-2 incidence was reduced in arm B versus arm C (adjusted risk ratio 0·76 [95% CI 0·63-0·92]; p=0·010); no significant change was shown between arm A versus arm C (0·89 [0·73-1·08]; p=0·199).InterpretationWe found little evidence of any change in sexual behaviour owing to the PopART interventions, and reassuringly for public health, we saw no evidence of sexual risk compensation. The findings do not help to explain the differences between the two intervention groups of the HPTN 071 (PopART) trial.FundingNational Institute of Allergy and Infectious Diseases, the National Institutes of Health, the International Initiative for Impact Evaluation (3ie), the Bill & Melinda Gates Foundation, the US President's Emergency Plan for AIDS Relief, and the Medical Research Council UK.

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.

Dataset Information

Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

Publications

Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

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