Response to antiretroviral therapy after a single, peripartum dose of nevirapine
Shahin Lockman, Roger L Shapiro, Laura M Smeaton, Carolyn Wester, Ibou Thior, Lisa Stevens, Fatima Chand, Joseph Makhema, Claire Moffat, Aida Asmelash, Patrick Ndase, Peter Arimi, Erik van Widenfelt, Loeto Mazhani, Vladimir Novitsky, Stephen Lagakos, Max Essex, Shahin Lockman, Roger L Shapiro, Laura M Smeaton, Carolyn Wester, Ibou Thior, Lisa Stevens, Fatima Chand, Joseph Makhema, Claire Moffat, Aida Asmelash, Patrick Ndase, Peter Arimi, Erik van Widenfelt, Loeto Mazhani, Vladimir Novitsky, Stephen Lagakos, Max Essex
Abstract
Background: A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants.
Methods: We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method.
Results: Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment.
Conclusions: Women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine. (ClinicalTrials.gov number, NCT00197587 [ClinicalTrials.gov].).
Copyright 2007 Massachusetts Medical Society.
Source: PubMed