Intrapartum Single-Dose Carbamazepine Reduces Nevirapine Levels Faster and May Decrease Resistance After a Single Dose of Nevirapine for Perinatal HIV Prevention

Muro, Eva P., Fillekes, Quirine, Kisanga, Elton R., L'homme, Rafaëlla, Aitken, Susan C., Mariki, Godfrey, Van der Ven, Andre J. A. M., Dolmans, Wil, Schuurman, Rob, Walker, A. Sarah, Gibb, Diana M., Burger, David M
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Background: World Health Organization guidelines recommend zidovudine + lamivudine for 7 days from labor onset in HIV-infected women receiving single-dose nevirapine (sdNVP) to cover prolonged subtherapeutic nevirapine concentrations. Although effective, this is complicated and does not eliminate resistance; alternative strategies could add benefit.

Methods: Antiretroviral-naive HIV-infected pregnant women aged 18–40 years, with CD4 >200 cells per cubic millimeter, able to regularly attend the antenatal clinics in Moshi, Tanzania, were enrolled 1:1 by alternate allocation to receive 200 mg sdNVP alone or in combination with open-label 400-mg single-dose carbamazepine (sdNVP/CBZ) at delivery ( NCT00294892). The coprimary outcomes were nevirapine plasma concentrations 1 week and nevirapine resistance mutations 6 weeks postpartum. Analyses were based on those still eligible at delivery.

Results: Ninety-seven women were assigned to sdNVP and 95 to sdNVP/CBZ during pregnancy, of whom 75 sdNVP and 83 sdNVP/CBZ were still eligible at delivery at study sites. The median (interquartile range) nevirapine plasma concentration was 1.55 (0.88–1.84) mg/L in sdNVP (n = 61) and 1.40 (0.93–1.97) mg/L in sdNVP/CBZ (n = 72) at delivery (P = 0.91), but 1 week later was significantly lower in sdNVP/CBZ [n = 63; 0.09 (0.05–0.20) mg/L] than in sdNVP [n = 52; 0.20 (0.09–0.31) mg/L; rank-sum: P = 0.004] (geometric mean ratio: 0.64, 95% confidence interval: 0.43 to 0.96; P = 0.03). Six weeks postpartum, nevirapine mutations were observed in 11 of 52 (21%) in sdNVP and 6 of 55 (11%) in sdNVP/CBZ (odds ratio = 0.46, 95% confidence interval: 0.16 to 1.34; P = 0.15).

Conclusions: Addition of single-dose carbamazepine to sdNVP at labor onset in HIV-infected, pregnant women did not affect nevirapine plasma concentration at delivery, but significantly reduced it 1 week postpartum, with a trend toward fewer nevirapine resistance mutations.