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Session 32-Themed Discussion
TD: HIV Drug Resistance in Breastfeeding Infants Exposed to ART
Thursday, 1-2 pm; Room 2005
Paper # 920    
Multi-class Drug Resistance Arises Frequently in HIV-infected Breastfeeding Infants Whose Mothers Initiate HAART Postpartum
Jessica Lidstrom1, L Guay1, P Musoke2, M Owor3, C Onyango-Makumbi3, J Church1, S Omer4, B Jackson1, and S Eshleman1
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Makerere Univ, Kampala, Uganda; 3Makerere Univ-Johns Hopkins Univ Res Collaboration, Kampala, Uganda; and 4Emory Univ, Atlanta, GA, US

Background:  Some HIV-infected women begin HAART postpartum for their own health. If their infants are breastfeeding, this may put the infants at risk of developing resistance to drugs in the mother’s HAART regimen. The SWEN study, performed in Uganda, Ethiopia, and India, compared the efficacy of single-dose nevirapine (sdNVP) alone to sdNVP plus an infant regimen of as long as 6 weeks of daily NVP prophylaxis (from day 8 until day 42) to prevent HIV transmission by breastfeeding; women in the study received sdNVP in labor. We analyzed ARV drug resistance in 7 HIV-infected, breastfeeding Ugandan infants in the SWEN study whose mothers started HAART post-partum.

Methods:  The infants in this study received either sdNVP (n = 2) or sdNVP plus daily NVP from day 8 until HIV infection was confirmed (NVP was stopped between day 18 and day 36, n = 5). The infants were diagnosed with HIV infection at birth (n = 3), at 2 weeks (n = 3), or at 6 weeks (n = 1). These infants did not receive HAART during the period studied. The mothers started HAART at 3 months (n = 6) or 6 months (n = 1) postpartum with either stavudine/lamivudine (3TC)/NVP (n = 3) or zidovudine/3TC/NVP (n = 4). HIV resistance was analyzed using the ViroSeq HIV Genotyping System.

Results:  At 1 year of age, all 7 infants were NVP resistant; 6 (85.7%) of 7 also had NRTI resistance. M184V, which is associated with resistance to 3TC and other NRTI, was detected in 6 of the 7 infants. Thymidine analog mutations (TAM, M41L, D67N, K70R, T215F) were also detected in 3 of 7 infants.

Conclusions:  HIV-infected breastfeeding infants can acquire resistance to ARV drugs in their mother’s HAART regimen. In this study, infants could have acquired NRTI resistance by transmission of NRTI-resistant HIV through breast milk, or by exposure to non-suppressive levels of NRTI in breast milk. Because these women and infants received NVP prophylaxis before the infant’s HIV infection was diagnosed, it is difficult to assess whether NVP prophylaxis, NVP in the mother’s HAART regimen, or both contributed to emergence of NVP resistance in the infants. Development of resistance to both NVP and NRTI (multi-class resistance) in HIV-infected infants is likely to significantly reduce their chance of responding to life-saving ARV therapy. Further studies are needed to assess the risks and benefits of initiating ARV treatment in breastfeeding women whose infants are HIV-infected.