Drug Resistance in Plasma and Breast Milk after Single-Dose Nevirapine in Subtype C HIV Type 1: Population and Clonal Sequence Analysis

Abstract

Single-dose nevirapine (SD NVP) reduces intrapartum HIV-1 transmission, but nonnucleoside reverse transcription (NNRTI) resistance mutations can emerge. Population sequencing among 32 subtype C HIV-1-infected, SD NVP-exposed Zimbawean women demonstrated NNRTI resistance in 25/32 (78%) women: 23/30 (77%) at 2 weeks, 11/31 (35%) at 8 weeks, and 5/27 (19%) at 24 weeks. A total of 447 unique TA clones (median = 28 per time point), from four women with resistance at 8 weeks but wild-type virus by population sequence at 24 weeks, identified NNRTI mutations in a median of 76% (range: 55–96%) of individual clones at 2 weeks, 48% (range: 33–80%) at 8 weeks, and 5% (range: 0–15%) by 24 weeks. NNRTI mutations in breast milk clones at 2 and weeks from one woman varied significantly from plasma. Population sequencing underestimates the diversity of NNRTI resistance mutations within minority populations following SD NVP in subtype C HIV-1 viral RNA in plasma and breast milk.