TY - JOUR
T1 - Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial
AU - Laeyendecker, Oliver
AU - Kulich, Michal
AU - Donnell, Deborah
AU - Komárek, Arnošt
AU - Omelka, Marek
AU - Mullis, Caroline E.
AU - Szekeres, Greg
AU - Piwowar-Manning, Estelle
AU - Fiamma, Agnes
AU - Gray, Ronald H.
AU - Lutalo, Tom
AU - Morrison, Charles S.
AU - Salata, Robert A.
AU - Chipato, Tsungai
AU - Celum, Connie
AU - Kahle, Erin M.
AU - Taha, Taha E.
AU - Kumwenda, Newton I.
AU - Karim, Quarraisha Abdool
AU - Naranbhai, Vivek
AU - Lingappa, Jairam R.
AU - Sweat, Michael D.
AU - Coates, Thomas
AU - Eshleman, Susan H.
PY - 2013/11/13
Y1 - 2013/11/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84893582417&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0078818
DO - 10.1371/journal.pone.0078818
M3 - Article
C2 - 24236054
AN - SCOPUS:84893582417
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e78818
ER -