Genotypic resistance analysis in women participating in PACTG 316 with HIV-1 RNA ≥ 10,000 copies/ml.
Int Conf AIDS 2000 Jul 9-14; 13:20 (abstract no.. LbOr14)
Sullivan J, Cunningham C, Dorenbaum A, Mofenson L, Culnane M, Gelber R, Britto P University of Massachusetts Medical School, Department of Pediatrics, Worcester, MA 01650. Fax: 508-856-5500, E-mail: John.Sullivan@umassmed.edu.
We assessed the prevalence of reverse transcriptase (RTI) and protease inhibitor (PI) resistance mutations at deliver and 6 weeks postpartum in women in Pediatric AIDS Clinical Trials Group (PACTG) 316. PACTG 316 is a blinded, ongoing 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 anti-retrovirals. Between 5/97-6/99, 712 women enrolled int PACTG 316. Plasma was analyzed from the 37 with delivery HIV RNA available and ≥ 10,000 copies/ml, and delivery and 6 week postpartum samples available. Since the study is ongoing, treatment (NVP vs placebo) is not yet unblinded. Genotypic resistance analysis was performed with TruGene- HIV-1 assay and OpenGene system (Visible Genetics Inc., Toronto, Canada). A NVP resistance mutation was present in 1 woman at delivery (Y181C), prior to study drug. NVP resistance mutations were detectable only after delivery in 3; all had the K103N mutation and 2 also had a second mutation (Y181C or V106A). No women received open label treatment with a non-nucleoside RTI prior to, or in the 6 weeks after delivery. Nucleoside RTI (NRTI) and PI mutations were common at delivery. NRTI primary or secondary mutations were found in 17; the most common were to 3TC and abacavir (11/37; all M184V or V/L), and zidovudine (9/37). Primary or secondary mutations associated with PI resistance included those to nelfinavir (27/37) and indinavir (20/37); 6 women had ≥ 3 PI mutations. In 3/37 women with plasma HIV-1 RNA ≥ 10,000 copies/ml, mutations associated with NVP resistance were detected after a single dose of NVP or placebo. It is unknown which of the 37 women received NVP in the ongoing, blinded trial. Mutations conferring resistance to NRTI and PI are also common. Further analysis is underway to determine resistance genotypes in women with HIV-1 RNA < 10,000 copies/ml.
Keywords: AEGIS, Nevirapine, HIV-1, Anti-HIV Agents, HIV Infections, Nelfinavir, Zidovudine, Dideoxynucleosides, Lamivudine, Indinavir, HIV, RNA-Directed DNA Polymerase, Prevalence, Mutation, Canada, abacavir, Human, Female, Infant, Child, genetics, AIDS 000709
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