Browsing by Author "Eshleman, Susan H."

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Antibody maturation in women who acquire HIV infection while using antiretroviral pre-exposure prophylaxis.
(Oxford University Press., 2015) Laeyendecker, Oliver.; Redd, Andrew D.; Nason, Martha.; Longosz, Andrew F.; Abdool Karim, Quarraisha.; Naranbhai, Vivek.; Garrett, Nigel Joel.; Eshleman, Susan H.; Abdool Karim, Salim Safurdeen.; Quinn, Thomas C.
Abstract available in pdf.
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.
Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial.
(Elsevier., 2011) Coovadia, Hoosen Mahomed.; Brown, Elizabeth R.; Fowler, Mary Glenn.; Chipato, Tsungai.; Moodley, Dhayendre.; Manji, Karim.; Musoke, Philippa.; Stranix-Chibanda, Lynda.; Chetty, Vani.; Fawzi, Wafaie.; Nakabiito, Clemensia.; Msweli, Lindiwe.; Kisenge, Rodrick Richard.; Guay, Laura.; Mwatha, Anthony.; Lynn, Diana J.; Eshleman, Susan H.; Richardson, Paul.; George, Kathleen.; Andrew, Philip.; Motenson, Lynne M.; Zwerski, Sheryl.; Maldonado, Yvonne.
Background. Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. Methods In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. Findings. Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3–1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3–3·6) of controls (difference 1·3%, 95% CI 0–2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3% vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. Interpretation. Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age.
Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.
(Lippincott Williams & Wilkins., 2013) Fowler, Mary Glenn.; Coovadia, Hoosen Mahomed.; Herron, Casey M.; Maldonado, Yvonne.; Chipato, Tsungai.; Moodley, Dhayendre.; Musoke, Philippa.; Aizire, Jim.; Manji, Karim.; Stranix-Chibanda, Lynda.; Fawzi, Wafaie.; Chetty, Vani.; Msweli, Lindiwe.; Kisenge, Rodrick Richard.; Brown, Elizabeth R.; Mwatha, Anthony.; Eshleman, Susan H.; Richardson, Paul.; Allen, Melissa.; George, Kathleen.; Andrew, Philip.; Zwerski, Sheryl.; Mofenson, Lynne Meryl.; Jackson, Jay Brooks.
Abstract available in PDF file.
Identification and validation of a multi-assay algorithm for cross-sectional HIV incidence estimation in populations with subtype C infection.
(International AIDS Society., 2018) Laeyendecker, Oliver.; Konikoff, Jacob.; Morrison, Douglas E.; Brookmeyer, Ronald.; Wang, Jing.; Celum, Connie Locke.; Morrison, Charles S.; Abdool Karim, Quarraisha.; Pettifor, Audrey E.; Eshleman, Susan H.
Abstract available in pdf.
Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants.
(Pediatric Infectious Disease Journal, 2013) Fogel, Jessica M.; Mwatha, Anthony.; Brown, Elizabeth R.; Richardson, Paul.; Chipato, Tsungai.; Alexandre, Michel.; Moodley, Dhayendre.; Elbireer, Ali.; Mirochnick, Mark.; George, Kathleen.; Mofenson, Lynne Meryl.; Zwerski, Sheryl.; Eshleman, Susan H.; Coovadia, Hoosen Mahomed.
Background: The HIV Prevention Trials Network (HPTN) 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV infection despite prophylaxis. Methods: HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher exact tests were used to evaluate associations between categorical variables. Results: NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIVuninfected at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a nonnucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all 4 of those infants by 6 months of age (4/4 = 100%). In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate antiretroviral treatment developed NVP resistance (P = 0.003). Conclusions: Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.
Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial.
(Public Library of Science., 2018) Landovitz, Raphael J.; Li, Sue.; Grinsztejn, Beatriz.; Dawood, Halima.; Liu, Albert Y.; Magnus, Manya.; Hosseinipour, Mina C.; Panchia, Ravindre.; Cottle, Leslie.; Chau, Gordon.; Richardson, Paul.; Marzinke, Mark Albert.; Hendrix, Craig W.; Eshleman, Susan H.; Zhang, Yinfeng.; Tolley, Elizabeth E.; Sugarman, Jeremy.; Kofron, Ryan.; Adeyeye, Adeola.; Burns, David.; Rinehart, Alex R.; Margolis, David.; Spreen, William R.; Cohen, Myron S.; McCauley, Marybeth.; Eron, Joseph J.
Abstract available in pdf.