712   Genotypic Resistance Analysis in Women Participating in PACTG 316 with HIV-1 RNA >400 Copies/ml.

C. K. Cunningham*¹, P. Britto², R. Gelber², A. Dorenbaum³, L. Mofenson⁴, M. Culnane⁵, J. L. Sullivan⁶, and the PACTG 316 Team.
¹SUNY Upstate Med. Univ., Syracuse, NY;²SDAC, Harvard Sch. of Publ. Health, Boston, MA;³Univ. of California, San Francisco;⁴PAMA Branch, NICHD, Bethesda, MD;⁵DAIDS, NIAID, NIH, Bethesda MD; and⁶Univ. of Massachusetts Med. Sch., Worcester.

Background:We assessed the prevalence of reverse transcriptase (RTI) and protease inhibitor (PI) resistance mutations at delivery and 6 weeks postpartum in women in Pediatric AIDS Clinical Trials Group (PACTG) 316. PACTG 316 is a blinded trial evaluating efficacy of single-dose nevirapine (NVP) vs. placebo to the mother at delivery and infant within 72 hours of birth to reduce HIV transmission in women receiving antenatal open-label antiretrovirals excluding non-nucleoside RTI. In June 2000 the study closed to new accrual, but infants born on study continue blinded follow-up. Between 5/97—6/00, 1052 women enrolled into PACTG 316 at US sites.

Methods:Plasma was analyzed from 104 women with delivery HIV RNA >400 copies/ml and amplified samples available from both delivery and 6 weeks postpartum. Genotypic resistance analysis was performed with TruGene HIV-1 assay and OpenGene system (Visible Genetics Inc., Toronto, Ontario, Canada).

Results:Of the 104 subjects studied, 51 were assigned to the NVP arm, with 46 having received study drug, and 53 were assigned to placebo. An NVP resistance mutation was present in 1 woman at delivery (Y181C), prior to study drug. NVP resistance mutations were detectable only after delivery in 6; all had the K103N mutation and 2 also had a second mutation (Y181C, V106A). Five of six with new NVP mutations were assigned to the NVP treatment arm, while 1 was on placebo; she received efavirenz treatment after delivery. Nucleoside RTI (NRTI) and PI mutations were common at delivery. NRTI primary or secondary mutations were found in 57/104 (55%); the most common were to 3TC and abacavir (47/104; all M184V or V/L), and zidovudine (20/104). Primary or secondary mutations associated with PI resistance included mutations at L63 (58/104; 65%) and V77 (29/104; 28%); 17 (16%) women had>3 PI mutations and 7 (7%) had>5 PI mutations.

Conclusions:5/46 (11%; 95% CI, 3.6%, 23.6%) women with plasma HIV-1 RNA >400 copies/ml have detectable mutations associated with NVP resistance after a single dose of NVP. Mutations conferring resistance to NRTI and PI are also common.