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Cross-sectional human immunodeficiency virus incidence estimation accounting for heterogeneity across communities.

ABSTRACT: Accurate estimation of human immunodeficiency virus (HIV) incidence rates is crucial for the monitoring of HIV epidemics, the evaluation of prevention programs, and the design of prevention studies. Traditional cohort approaches to measure HIV incidence require repeatedly testing large cohorts of HIV-uninfected individuals with an HIV diagnostic test (eg, enzyme-linked immunosorbent assay) for long periods of time to identify new infections, which can be prohibitively costly, time-consuming, and subject to loss to follow-up. Cross-sectional approaches based on the usual HIV diagnostic test and biomarkers of recent infection offer important advantages over standard cohort approaches, in terms of time, cost, and attrition. Cross-sectional samples usually consist of individuals from different communities. However, small sample sizes limit the ability to estimate community-specific incidence and existing methods typically ignore heterogeneity in incidence across communities. We propose a permutation test for the null hypothesis of no heterogeneity in incidence rates across communities, develop a random-effects model to account for this heterogeneity and to estimate community-specific incidence, and provide one way to estimate the coefficient of variation. We evaluate the performance of the proposed methods through simulation studies and apply them to the data from the National Institute of Mental Health Project ACCEPT, a phase 3 randomized controlled HIV prevention trial in Sub-Saharan Africa, to estimate the overall and community-specific HIV incidence rates.

SUBMITTER: Xu Y

PROVIDER: S-EPMC6690817 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Cross-sectional human immunodeficiency virus incidence estimation accounting for heterogeneity across communities.

Xu Yuejia Y Laeyendecker Oliver O Wang Rui R

Biometrics 20190901 3

Accurate estimation of human immunodeficiency virus (HIV) incidence rates is crucial for the monitoring of HIV epidemics, the evaluation of prevention programs, and the design of prevention studies. Traditional cohort approaches to measure HIV incidence require repeatedly testing large cohorts of HIV-uninfected individuals with an HIV diagnostic test (eg, enzyme-linked immunosorbent assay) for long periods of time to identify new infections, which can be prohibitively costly, time-consuming, and ...[more]

PMID: 30746695

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Project description:BackgroundAssessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers.MethodsWe compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-?), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use.ResultsDetectable HIV and HCV RNA (OR?=?2.49; 95% CI?=?1.05-5.89) and detectable HCV RNA alone (2.95; 1.08-8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90-31.97) and TNF-? (7.70; 1.42-41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84).ConclusionsDetectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.

Project description:IntroductionCross-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.

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Cross-sectional human immunodeficiency virus incidence estimation accounting for heterogeneity across communities.

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Cross-sectional human immunodeficiency virus incidence estimation accounting for heterogeneity across communities.

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