516   Selection of Nevirapine Resistance (NVP^R) Mutations in Ugandan Women and Infants Receiving NVP Prophylaxis To Prevent HIV-1 Vertical Transmission (HIVNET-012).

S. H. Eshleman*¹, M. Mracna¹, L. Guay¹, M. Deseyve², S. Cunningham¹, P. Musoke^3., F. Mmiro³, and J. B. Jackson¹.
¹Johns Hopkins Med. Inst., Baltimore, MD;²Fred Hutchinson Cancer Res. Ctr., Seattle, WA; and³Makerere Univ., Kampala, Uganda.

Background:In HIVNET 012, treatment-naïve Ugandan women and infants received a single dose of NVP to prevent HIV-1 vertical transmission. Women received 200 mg NVP at the onset of labor, and infants received 2 mg/kg NVP within 72 hours of birth. Thirty-six of 311 infants were HIV-1 infected by age 6 weeks despite NVP prophylaxis. We examined the impact of NVP administration on the development of NVP^Rin this cohort.

Methods:Plasma collected 6 weeks after delivery from 95 women, including 31 whose infants were HIV-1 infected, and from 20 of the infected infants was analyzed. HIV-1 genotyping was performed with the Applied Biosystems ViroSeq HIV-1 Genotyping System.

Results:NVP^Rmutations were detected in 17/95 (18%) of women (7/31 (23%) vs. 10/64 (16%) of women whose infants were or were not HIV-1 infected, p = 0.41). Samples were obtained from 5 of those 17 women 12—18 months after delivery. All 5 follow-up samples lacked NVP^Rmutations. Women who developed NVP^Rmutations had significantly higher baseline viral loads (median: 63,465 vs. 36,266 c/ml, p = 0.01) and significantly lower baseline CD4 counts (median: 230 vs. 426 cells/ml, p = 0.002) compared to those who did not develop NVP^R. There was no association between maternal death and NVP^R

after adjusting for baseline viral load. NVP^Rmutations were also detected in 9/20 (45%) of the infected infants. NVP^Rmutations were no longer detectable in 3 of 7 available infant samples at 14—16 weeks postpartum. K103N was the most frequent NVP^Rmutation in the women, whereas Y181C was the most frequent NVP^Rmutation in the infants.

Conclusions:Single-dose NVP prophylaxis is associated with selection of NVP^RHIV-1 in women and infants. HIV-1 genotypes suggest independent selection of HIV-1 with NVP^Rmutations in infants, rather than transmission of NVP^RHIV-1 from the mothers. NVP^Rmutations were detected more frequently in 6-week samples from women with higher baseline viral loads and lower baseline CD4 counts. The mutations appear to be fading from detection in the mothers and infants over time and were not associated with maternal death.