This case-control study involving the Promoting Maternal and Infant Survival Everywhere (PROMISE) cohort examined HIV genotypes of participants who transmitted HIV compared to participants who did not transmit to their infants. Investigators aimed to assess if maternal plasma HIV drug resistance is associated with increased transmission risk and to describe dynamics of NNRTI resistance in infants who acquired HIV. 48 infants were identified as having acquired HIV in utero/peripartum, compared with 37 infants who acquired HIV via breastfeeding. Adjusted analyses of in utero/peripartum transmission cases indicated that maternal HIV drug resistance, maternal plasma HIV RNA at infant diagnosis, enrollment CD4 count, and antepartum regimens were not associated with transmission. By contrast, for infants who acquired HIV via breastfeeding, maternal drug resistance and high maternal HIV RNA at time of infant diagnosis were independently associated with transmission. At time of diagnosis, 52.8% of infants who acquired HIV via breastfeeding were found to have HIV drug resistance (compared to only 12.2% of infants with in utero/peripartum transmission). Mutations affecting in utero/peripartum transmission infants included single NNRTI mutations, whereas mutations affecting breastfeeding transmission infants included single NRTI, single NNRTI, multiple NNRTI, or dual-class mutations.