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Oral Abstracts and Mini-Lecture|
Transmission, Selection, and Persistence of Drug-Resistant Virus
Monday, 10 am - 12:15 pm
Presentation Time: 11:30 am
Background: Single-dose nevirapine (SD-NVP) is efficacious in preventing HIV mother-to-child transmission (PMTCT) but resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTI) are detectable in the postpartum period in a substantial proportion of mothers. Their clinical significance is unknown.
Methods: Immunocompromized women participating in PHPT2, a randomized trial in Thailand, which showed an 80% decrease in perinatal HIV with the addition of intrapartum NVP to zidovudine prophylaxis, were offered antiretroviral therapy. A 10-day postpartum sample was assessed for RT mutations (ViroSeq HIV-1 Genotyping System; WWW.IASUSA.ORG), first in a random sample of 90 women stratified on CD4 and virus load; and then in all women who subsequently received an NNRTI-based regimen and for whom viral load could be assayed at 3 and/or 6 (+ 1.5) months (Cobas Amplicor HIV-1 v1.5 Roche).
Results: NNRTI-resistance mutations were detectable in 18% of the random sample of women (K103N, G190A, or Y181C). At 3 months, 80% of the 66 women with at least one mutation, 87% of the 112 SD-NVP exposed women with no mutation and 88% of the 41 non exposed women had a viral load <400 copies/mL (viral load <50: 45%, 46%, and 54%). At 6 months, 68% of the 50 women with at least one mutation, 80% of the 92 exposed women without mutation and 85% of the 27 non exposed women had a viral load <400 (p for trend = 0.057) (viral load <50: 38%, 50%, 74%; p for trend = 0.0034). Of SD-NVP-exposed women without and with mutations who started therapy more than 6 months after delivery, 91% and 77%, had a viral load <400, vs 69% and 58% of those who started earlier (p = 0.006) (viral load <50: p = NS).
Conclusions: Mothers exposed to SD-NVP for PMTCT experienced a lower virological success rate of subsequent NNRTI-based therapy compared to non-exposed mothers. However, a clinically meaningful proportion of women still achieved virological success at 6 months even in the presence of mutations. Importantly, later initiation of therapy after NVP exposure was associated with an improved virological response. These results suggest that drug-resistance mutations that arise following SD-NVP exposure have an effect on the efficacy of subsequent NNRTI-based therapies. They also provide insight and demonstrate the necessity for further development of synergistic strategies which will maximize benefit of subsequent antiretroviral therapy for the mother while preserving the remarkable achievements of potent antiretroviral therapy for PMTCT.
Keywords: Nevirapine; Resistance; Perinatal