Background:  The Kisumu Breastfeeding Study is assessing the safety and efficacy of zidovudine (AZT), lamivudine (3TC), and either nevirapine (NVP) or nelfinavir (NFV) from 34 weeks’ gestation through 24 weeks’ postpartum for prevention of mother-to-child transmission (PMTCT) among HIV-infected breastfeeding mothers. We previously reported that NVP and 3TC given to mothers are transmitted to the infant via breastfeeding in quantities sufficient to have biologic effect. Here we evaluated whether this exposure could contribute to HIV resistance among infected infants.

Methods:  We tested all infants for HIV using the DNA polymerase chain reaction (PCR) at multiple study visits and retrospectively evaluated plasma RNA viral load from all PCR-positive infants. We used the Viroseq^TM HIV-1 Genotyping system to genotype HIV from infants and their mothers if viral load was >1000 copies/mL.

Results:  Of 502 infants, 29 (5.8%) were found to be HIV-infected, of whom the first positive HIV PCR was before 24 weeks for 24 (83%) infants. Antiretrovirals (ARV) taken by the mothers of these 24 infants included NVP for 14 (58%) and NFV for 10 (42%). Genotypic resistance results are shown in the table. Genotypic resistance was detected among 16 infants including 6 (43%) of 14 infants of mothers taking NVP and 10 (100%) of 10 infants of mothers taking NFV (p = 0.006).  Genotypic resistance mutations to NRTI were M184V (n = 13), K65R (n = 4), D67N (n = 2), and T215Y (n = 2), and to NNRTI were Y181C (n = 3), K103N (n = 2), G190A (n = 2), and K101E (n = 1). Among infants exposed to maternal NVP, 4 (67%) of 6 infants with resistance had a NRTI mutation and all 6 had an NNRTI mutation. Among infants exposed to maternal NFV, 10 (100%) of 10 infants had a NRTI mutation, but none had a major protease inhibitor mutation.

Conclusions:  Among infants who became HIV-infected by the first 6 weeks of life, ARV resistance was initially not detected suggesting resistant virus may not have been transmitted from the mother. However, resistance emerged during the breastfeeding period, likely due to the transfer of ARV from breast-milk. Differing HIV resistance patterns depending on the mothers’ treatment may have implications for the choice of ARV for mothers during the breastfeeding period and for subsequent treatment of infants who become HIV-infected.