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.
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