Dataset Information

Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial.

ABSTRACT:

Background

Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment.

Methods and findings

Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept.

Conclusions

In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation.

SUBMITTER: Laeyendecker O

PROVIDER: S-EPMC3827276 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial.

Laeyendecker Oliver O Kulich Michal M Donnell Deborah D Komárek Arnošt A Omelka Marek M Mullis Caroline E CE Szekeres Greg G Piwowar-Manning Estelle E Fiamma Agnes A Gray Ronald H RH Lutalo Tom T Morrison Charles S CS Salata Robert A RA Chipato Tsungai T Celum Connie C Kahle Erin M EM Taha Taha E TE Kumwenda Newton I NI Karim Quarraisha Abdool QA Naranbhai Vivek V Lingappa Jairam R JR Sweat Michael D MD Coates Thomas T Eshleman Susan H SH

PloS one 20131113 11

<h4>Background</h4>Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment.<h4>Methods and ...[more]

PMID: 24236054

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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.

Project description:BackgroundMulti-assay algorithms (MAAs) are used to estimate population-level HIV incidence and identify individuals with recent infection. Many MAAs use low viral load (VL) as a biomarker for long-term infection. This could impact incidence estimates in settings with high rates of early HIV treatment initiation. We evaluated the performance of two MAAs that do not include VL.MethodsSamples were collected from 219 seroconverters (infected < 1 year) and 4376 non-seroconverters (infected > 1 year) in the HPTN 071 (PopART) trial; 28.8% of seroconverter samples and 73.2% of non-seroconverter samples had VLs ≤ 400 copies/mL. Samples were tested with the Limiting Antigen Avidity assay (LAg) and JHU BioRad-Avidity assays. Antibody reactivity to two HIV peptides was measured using the MSD U-PLEX assay. Two MAAs were evaluated that do not include VL: a MAA that includes the LAg-Avidity assay and BioRad-Avidity assay (LAg + BR) and a MAA that includes the LAg-Avidity assay and two peptide biomarkers (LAg + PepPair). Performance of these MAAs was compared to a widely used MAA that includes LAg and VL (LAg + VL).ResultsThe incidence estimate for LAg + VL (1.29%, 95% CI: 0.97-1.62) was close to the observed longitudinal incidence (1.34% 95% CI: 1.17-1.53). The incidence estimates for the other two MAAs were higher (LAg + BR: 2.56%, 95% CI 2.01-3.11; LAg + PepPair: 2.84%, 95% CI: 1.36-4.32). LAg + BR and LAg + PepPair also misclassified more individuals infected > 2 years as recently infected than LAg + VL (1.2% [42/3483 and 1.5% [51/3483], respectively, vs. 0.2% [6/3483]). LAg + BR classified more seroconverters as recently infected than LAg + VL or LAg + PepPair (80 vs. 58 and 50, respectively) and identified ~ 25% of virally suppressed seroconverters as recently infected.ConclusionsThe LAg + VL MAA produced a cross-sectional incidence estimate that was closer to the longitudinal estimate than two MAAs that did not include VL. The LAg + BR MAA classified the greatest number of individual seroconverters as recently infected but had a higher false recent rate.

Project description:BackgroundHIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations.MethodsWe analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis.FindingsBetween Oct 1, 2012, and Dec 19, 2013, we recruited 26,503 participants, 12,022 men who have sex with men and 14,481 people who inject drugs. Median incidence of HIV was 0·87% (IQR 0·40-1·17) in men who have sex with men and 1·43% (0·60-4·00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0·81, 95% CI 0·62-0·91; p<0·0001) than all other measures, although correlation was significant with aware viral load (0·59, 0·27-0·79; p=0·001), population viral load (0·51, 0·16-0·74; p=0·007), and population ART coverage (-0·54, -0·76 to -0·20; p=0·004). In-care viral load was not correlated with HIV incidence (0·29, -0·10 to 0·60; p=0·14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4·34%, and ART use in HIV-positive individuals would need to increase by 19·5%.InterpretationPrevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme.FundingUS National Institutes of Health, Elton John AIDS Foundation.

Dataset Information

Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial.

Background

Methods and findings

Conclusions

Publications

Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial.

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