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.2016-09-132016-09-1320132013Fogel, J.M.; Mwatha, A.; Richardson, P.; Brown, E.R.; Chipato, T.; Alexandre, M.; Moodley, D.; Elbireer, A.; Mirochnick, M.; George, K.; Mofenson, L.M.; Zwerski, S.; Coovadia, H.M.; Eshleman, S.H. 2013. Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants. The Pediatric infectious disease journal 32(4), 164-169..http://dx.doi.org/10.1097/INF.0b013e31827f44eehttp://hdl.handle.net/10413/13343The HPTN 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP 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.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.enNevirapine resistance.Prevention of mother-to-child transmission.Extended nevirapine.HIV.Peer reviewed journal article