Effect of 7 days of phenytoin on the pharmacokinetics of and the development of resistance to single-dose nevirapine for perinatal HIV prevention: a randomized pilot trial

To confirm whether 7 days of phenytoin, an enzyme inducer, would decrease the elimination half-life of single-dose nevirapine and to investigate its effect on the development of nevirapine resistance in pregnant, HIV-infected women. In a pharmacokinetic pilot trial (NCT01187719), HIV-infected, antir...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2013-11, Vol.68 (11), p.2609-2615
Main Authors: Fillekes, Quirine, Muro, Eva P, Chunda, Catherine, Aitken, Susan, Kisanga, Elton R, Kankasa, Chipepo, Thomason, Margaret J, Gibb, Diana M, Walker, A Sarah, Burger, David M
Format: Article
Language:English
Subjects:
Adult
Age
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - pharmacokinetics
Anti-HIV Agents - pharmacology
Anticonvulsants - administration & dosage
Drug dosages
Drug Interactions
Drug resistance
Drug Resistance, Viral
Enzymes
Female
Half-Life
HIV
HIV - drug effects
HIV - isolation & purification
HIV Infections - prevention & control
HIV Infections - transmission
Human immunodeficiency virus
Humans
Infectious Disease Transmission, Vertical - prevention & control
Nevirapine - administration & dosage
Nevirapine - pharmacokinetics
Nevirapine - pharmacology
Phenytoin - administration & dosage
Pilot Projects
Pregnancy
Tanzania
Women
Young Adult
Zambia
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Summary:To confirm whether 7 days of phenytoin, an enzyme inducer, would decrease the elimination half-life of single-dose nevirapine and to investigate its effect on the development of nevirapine resistance in pregnant, HIV-infected women. In a pharmacokinetic pilot trial (NCT01187719), HIV-infected, antiretroviral (ARV)-naive pregnant women ≥18 years old from Zambia and Tanzania and with CD4 cell counts >350 cells/mm(3) were randomized 1 : 1 to a control (zidovudine pre-delivery, single-dose nevirapine/zidovudine/lamivudine at delivery and zidovudine/lamivudine for 7 days post-delivery) or an intervention (control plus 184 mg of phenytoin once daily for 7 days post-delivery) group. Primary endpoints were the pharmacokinetics of and resistance to nevirapine. Thirty-five and 37 women were allocated to the control and intervention groups, with median (IQR) ages of 27 (23-31) and 27 (23-33) years, respectively. Twenty-three and 23 women had detectable nevirapine levels at delivery and subsequent samples in the control and the intervention groups, respectively. Geometric mean (GM) (95% CI) plasma levels of nevirapine at delivery were 1.02 (0.58-1.78) mg/L and 1.14 (0.70-1.86) mg/L in the control and intervention groups, respectively (P = 0.76). One week after delivery, 0/23 (0%) and 15/22 (68%) control and intervention mothers, respectively, had undetectable levels of nevirapine (
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkt246