Browsing by Author "Mullis, Caroline E."

Now showing 1 - 2 of 2

Development of methods for cross-sectional HIV incidence estimation in a large, community randomized trial.
(PLOS ONE., 2013) Laeyendecker, Oliver.; Kulich, Michal.; Donnell, Deborah.; Koma´rek, Arnosˇt.; Omelka, Marek.; Mullis, Caroline E.; Szekeres, Greg.; Piwowar-Manning, Estelle.; Fiamma, Agnes.; Gray, Ronald H.; Lutalo, Tom.; Morrison, Charles S.; Salata, Robert A.; Chipato, Tsungai.; Celum, Connie Locke.; Kahle, Erin M.; Taha, Taha E.; Kumwenda, Newton I.; Abdool Karim, Quarraisha.; Naranbhai, Vivek.; Lingappa, Jairam R.; Sweat, Michael D.; Coates, Thomas.; Eshleman, Susan H.
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.
Limited HIV-1 superinfection in seroconverters from the CAPRISA 004 Microbicide trial.
(American Society for Microbiology., 2014) Redd, Andrew D.; Mullis, Caroline E.; Wendel, Sarah K.; Sheward, Daniel J.; Martens, Craig.; Bruno, Daniel.; Werner, Lise.; Garrett, Nigel Joel.; Abdool Karim, Quarraisha.; Williamson, Carolyn.; Porcella, Stephen F.; Quinn, Thomas C.; Abdool Karim, Salim Safurdeen.
HIV-1 superinfection (SI) occurs when an infected individual acquires a distinct new viral strain. The rate of superinfection may be reflective of the underlying HIV risk in a population. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 clinical trial demonstrated that women who used a tenofovir-containing microbicide gel had lower rates of HIV infection than women using a placebo gel. Women who contracted HIV-1 during the trial were screened for the occurrence of superinfection by next-generation sequencing of the viral gag and env genes. There were two cases (one in each trial arm) of subtype C superinfection identified from the 76 women with primary infection screened at two time points (rate of superinfection, 1.5/100 person-years). Both women experienced a >0.5-log increase in viral load during the window when superinfection occurred. The rate of superinfection was significantly lower than the overall primary HIV incidence in the microbicide trial (incidence rate ratio [IRR], 0.20; P=0.003). The women who seroconverted during the trial reported a significant increase in sexual contact with their stable partner 4 months after seroconversion (P<0.001), which may have lowered the risk of superinfection in this population. The lower frequency of SI compared to the primary incidence is in contrast to a report from a general heterosexual African population but agrees with a study of high-risk women in Kenya. A better understanding of the rate of HIV superinfection could have important implications for ongoing HIV vaccine research.