Paper # 761 
Initiation of ART in Women after Delivery Can Induce Multi-class Drug Resistance in Breastfeeding HIV-infected Infants: PEPI-Malawi Trial
Jessica Fogel*1, Q Li2, T Taha3, D Hoover4, N Kumwenda3, L Mofenson5, J Kumwenda6, MG Fowler1, M Thigpen7, and S Eshleman1
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Natl Human Genome Res Inst, NIH, Baltimore, MD, US; 3Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; 4Rutgers Univ, Piscataway, NJ, US; 5Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; 6Univ of Malawi Coll of Med, Blantyre; and 7CDC, Atlanta, GA, US
Background: The World Health Organization (WHO)
recommends initiation of HAART for HIV+ adults with CD4 cell counts
<350 cells/mL or WHO stage 3 or 4
disease, including pregnant and lactating women. While ART is critical for
maternal health, it may put HIV+ breastfeeding infants at risk for
acquiring resistance to drugs in the maternal treatment regimen. We analyzed drug
resistance in all HIV+ infants in the PEPI-Malawi trial whose
mothers started HAART by 12 months post-partum (nevirapine [NVP] /stavudine/lamivudine).
Methods: In PEPI-Malawi, pregnant HIV+ women who
presented >4 hours before anticipated delivery received single-dose NVP
(sdNVP). Infants received 1 of 3 regimens for prevention of HIV transmission:control:
sdNVP + 1 week zidovudine (ZDV), control + ≤14 weeks of daily infant
NVP, control + up to 14 weeks of daily infant NVP+ZDV. In the first post-partum
year, 59 women with HIV+ infants started HAART for their own health.
The first infant sample collected after the mother reported HAART use was
analyzed using the ViroSeq HIV Genotyping System; results were obtained for 40
of 45 available samples. Excluded from analysis were 3 infants who were also
receiving HAART. The remaining 37 infants were included in the analysis of
multi-class resistance. Categorical variables were compared by exact or trend
tests; continuous variables were compared using rank tests.
Results: Multi-class resistance was detected in 11
(29.7%) of 37 infants. It was detected more frequently in infants whose mothers
first reported HAART use by 14 weeks post-partum (8 of 13, 61.5%) than in
infants whose mothers first reported HAART use between 14 weeks and 6 months
post-partum (3 of 13, 23.1%) or after 6 months post-partum (0 of 11, p =
0.0009, Cochran-Armitage trend test). Multi-class resistance was detected in 11
(50%) of 22 infants whose mothers were exclusively breastfeeding when they
first reported HAART use; it was not detected in any infants whose mothers
reported that they were providing mixed feeding or were not breastfeeding when
they first reported HAART use (p = 0.003, Cochran-Armitage trend test).
Conclusions: Post-partum maternal HAART initiation
was associated with acquisition of multi-class resistance in HIV+
breastfeeding infants. The risk was higher among infants whose mothers
initiated HAART closer to the time of delivery or were still exclusively
breastfeeding when they first reported HAART use.
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