Browsing by Author "Bobat, Raziya"

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    Antiretroviral Treatment for Children with Peripartum Nevirapine Exposure
    (New England Journal of Medicine, 2010) Palumbo, Paul; Lindsey, Jane C.; Hughes, Michael D.; Cotton, Mark F.; Bobat, Raziya; Meyers, Tammy; Dangarembizi, Mutsawashe Bwakura; Chi, Benjamin H.; Musoke, Philippa; Kamthunzi, Portia; Schimana, Werner; Purdue, Lynette; Eshleman, Susan H.; Abrams, Elaine J.; Millar, Linda; Petzold, Elizabeth; Mofenson, Lynne M.; Philippe, Patrick Jean; Violari, Avy
    Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown.We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events.Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151. opens in new tab.)
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    Prevention of HIV-1 transmission through breastfeeding: Efficacy and safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV-1-infected women with high CD4 cell count (IMPAACT PROMISE): a randomized, open label, clinical trial
    (Journal of acquired immune deficiency syndromes, 2018) Flynn, Patricia M.; Taha, Taha E.; Cababasay, Mae; Glenn Fowler, Mary; Mofenson, Lynne M.; Owor, Maxensia; Fiscus, Susan; Stranix-Chibanda, Lynda; Coutsoudis, Anna; Gnanashanmugam, Devasena; Chakhtoura, Nahida; McCarthy, Katie; Mukuzunga, Cornelius; Makanani, Bonus; Moodley, Dhayendre; Nematadzira, Teacler; Kusakara, Bangini; Patil, Sandesh; Vhembo, Tichaona; Bobat, Raziya; Mmbaga, Blandina T.; Masenya, Maysseb; Nyati, Mandisa; Theron, Gerhard; Mulenga, Helen; Butler, Kevin; Shapiro, David E.
    No randomized trial has directly compared the efficacy of prolonged infant antiretroviral prophylaxis versus maternal antiretroviral therapy (mART) for prevention of mother-to-child transmission throughout the breastfeeding period. Setting—Fourteen sites in sub-Saharan Africa and India. Methods—A randomized, open label strategy trial was conducted in HIV-1-infected women with CD4 counts ≥350 cells/mm3 (or ≥country-specific ART threshold if higher) and their breastfeeding HIV-1-uninfected newborns. Randomization at 6-14 days postpartum was to mART or infant nevirapine prophylaxis (iNVP) continued until 18 months post-delivery or breastfeeding cessation, infant HIV-1 infection, or toxicity, whichever occurred first. The primary efficacy outcome was confirmed infant HIV-1 infection. Efficacy analyses included all randomized mother-infant pairs except those with infant HIV-1 infection at entry. Results—Between June 2011-October 2014, 2431 mother-infant pairs were enrolled; 97% of women were WHO Clinical Stage I, median screening CD4 count 686 cells/mm3. Median infant gestational age/birthweight were 39 weeks/2.9 kilograms. Seven of 1219 (0.57%) and seven of 1211 (0.58%) analyzed infants in the mART and iNVP arms, respectively, were HIV-infected (hazard ratio [HR] 1.0, 96% repeated confidence interval 0.3-3.1); infant HIV-free survival was high (97.1%, mART and 97.7%, iNVP, at 24 months). There were no significant differences between arms in median time to breastfeeding cessation (16 months) or incidence of severe, life-threatening or fatal adverse events for mothers or infants (14 and 42 per 100 person-years, respectively). Conclusion—Both mART and iNVP prophylaxis strategies were safe and associated with very low breastfeeding HIV-1 transmission and high infant HIV-1-free survival at 24 months.