B9. THE OCCURRENCE OF POTENTIALLY SERIOUS TOXICITIES TO NEVIRAPINE AND ZIDOVUDINE IN HIV-INFECTED, POST-PARTUM WOMEN WITH HIGH CD4 COUNTS, AND IN THEIR HIV-UNINFECTED INFANTS.
Bramson B1, Chasela C1, Ahmed Y2, Hosseinipour M1 Kourtis A2, Martinson F1, Kazembe P3, Hoffman I1, Jamieson D2, van der Horst C1
1UNC Project, Lilongwe, Malawi; 2Centers for Disease Control, Atlanta, USA; 3Kamuzu Central Hospital
Objective: We describe the occurrence of potentially serious toxicities to nevirapine and zidovudine when given to breastfeeding women with high CD4 counts or their HIV-uninfected infants in a breastfeeding transmission prevention trial in Malawi.
Methods: The Breastfeeding Antiretroviral Nutrition Study (BAN) is a prospective randomized controlled factorial clinical trial of an antiretroviral and a nutritional intervention interventional trial. In addition to peripartum prophylaxis, mother-infant pairs are randomly assigned at birth to one of three groups: 1) maternal zidovudine/lamivudine/nevirapine for 28 weeks, , 2) daily infantnevirpine for 28 weeks, or 3) no additional prophylaxis. HIV- infected pregnant women with baseline CD4 counts >200 cells/microliter are eligible for randomization. All enrolled subjects were assessed regularly for signs, symptoms, or laboratory values suggesting anti-retroviral drug toxicities, with pre-determined criteria for changing or discontinuing ARV treatment in response to toxicities.
Results: From 24 April 2004 through 31 January 2005, thirty-eight were randomized to receive maternal anti-retroviral drugs and thirty-seven infants were randomized to receive daily nevirapine.One woman was discontinued in the first week due to inability to breastfeed. Of the remaining 37 women, 8 (21.6%) were changed from nevirapine to nelfinavir in response to cutaneous or hepatic toxicities. Five of 37 women (13.5%) were changed from zidovudine to stavudine in response to anemia and neutropenia. One infant of 37 (2.7%) receiving nevirapine was switched to nelfinavir for possible hepatomegaly.
Conclusions: When nevirapine is used in post-partum women with CD4 counts > 200 cells/microliter, women should be monitored closely for cutaneous and hepatic toxicities. In addition, when zidovudine is used in this population, women should be monitored closely for hematologic toxicicties.
Recommendations: Nevirapine should be used cautiously in women with high CD4 cell counts and if given, requires close clinical monitoring. The use of zidovudine requires laboratory monitoring.