Browsing by Author "Piwowar-Manning, Estelle."

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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.
Safety and effectiveness of BufferGel and 0.5% PRO 2000 gel for the prevention of HIV infection in women.
(Lippincott Williams & Wilkins., 2010) Abdool Karim, Salim Safurdeen.; Richardson, Barbra Ann.; Ramjee, Gita.; Hoffman, Irving F.; Chirenje, Zvavahera Mike.; Taha, Taha E.; Kapina, Muzala.; Maslankowski, Lisa.; Coletti, Anne S.; Profy, Albert.; Moench, Thomas R.; Piwowar-Manning, Estelle.; Masse, Benoit.; Hillier, Sharon Louise.; Soto-Torres, Lydia.
Objective: To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male-to-female HIV transmission. Design: Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open-label no gel arm. Methods: Study participants from Malawi, South Africa, Zambia, Zimbabwe, and the USA were instructed to apply study gel up to 1 h before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up. Results: The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 gel, BufferGel, placebo gel, and no gel arms were 2.70, 4.14, 3.91, and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 gel arm was lower than the placebo gel arm (hazard ratio = 0.7, P=0.10) and the no gel arm (hazard ratio = 0.67, P=0.06). HIV incidence rates were similar in the BufferGel and both placebo gel (hazard ratio =1.10, P=0.63) and no gel control arms (hazard ratio =1.05, P=0.78). HIV incidence was similar in the placebo gel and no gel arms (hazard ratio =0.97, P=0.89). Conclusion: The 0.5% PRO2000 gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the Microbicide Development Programme (MDP) 301 trial have confirmed that 0.5% PRO2000 gel has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were well tolerated.