PURPOSE: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women. METHODS: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. RESULTS: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. CONCLUSIONS: Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy.
PURPOSE: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infectedwomen. METHODS: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. RESULTS: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. CONCLUSIONS:Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy.
Authors: Anna H Tran; Brookie M Best; Alice Stek; Jiajia Wang; Edmund V Capparelli; Sandra K Burchett; Regis Kreitchmann; Kittipong Rungruengthanakit; Kathleen George; Tim R Cressey; Nahida Chakhtoura; Elizabeth Smith; David E Shapiro; Mark Mirochnick Journal: J Acquir Immune Defic Syndr Date: 2016-07-01 Impact factor: 3.731
Authors: Ahizechukwu C Eke; Shelley A McCormack; Brookie M Best; Alice M Stek; Jiajia Wang; Regis Kreitchmann; David Shapiro; Elizabeth Smith; Lynne M Mofenson; Edmund V Capparelli; Mark Mirochnick Journal: J Clin Pharmacol Date: 2018-10-25 Impact factor: 3.126