Browsing by Author "Fawzi, Wafaie."

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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.
HIV disease progression in the first year after delivery among african women followed in the HPTN 046 clinical trial.
(Lippincott Williams & Wilkins., 2013) Watts, Heather D.; Brown, Elizabeth R.; Maldonado, Yvonne.; Herron, Casey.; Chipato, Tsungai.; Reddy, Leanne.; Moodley, Dhayendre.; Nakabiito, Clemensia.; Manji, Karim.; Fawzi, Wafaie.; George, Kathleen.; Richardson, Paul.; Zwerski, Sheryl.; Coovadia, Hoosen Mahomed.; Fowler, Mary Glenn.
Background: Starting lifelong antiretroviral therapy (ART) in HIV-infected pregnant women may decrease HIV progression and transmission, but adherence after delivery may be difficult, especially for asymptomatic women. We evaluated disease progression among HIV-infected women not on ART with CD4⁺ lymphocyte counts above 200 cells per microliter at delivery. Methods: We analyzed risk of death, progression to AIDS (stage IV or CD4 < 200 cells per microliter), or to CD4⁺ count <350 1 year after delivery among postpartum women enrolled to a prevention of breastfeeding transmission trial using the Kaplan–Meier method. In the primary analysis, women were censored if ART was initiated. Results: Among 1285 women who were not WHO stage IV or less at 6 weeks postpartum, 49 (4.3%) progressed to stage IV/CD4 <200 cells per microliter or death by 1 year. Progression to CD4 <200 cells per microliter or death occurred among 16 (4.3%) of 441 women with CD4 count of 350–549 cells per microliter and 10 (1.6%) of 713 with CD4 counts >550 cells per microliter at delivery. CD4 <350 cells per microliter by 12 months postpartum occurred among 116 (37.0%) of 350 women with CD4 count 400–549 cells per microliter and 48 (7.4%) of 713 with CD4 count >550 cells per microliter at delivery. Conclusions: Progression to AIDS or CD4 count <350 cells per microliter is uncommon through 1 year postpartum for women with CD4 counts over 550 cells per microliter at delivery, but occurred in over one third of those with CD4 counts under 550 cells per microliter. ART should be continued after delivery or breastfeeding among women with CD4 counts <550 cells per microliter if follow-up and antiretroviral adherence can be maintained.