Nevirapine plasma concentrations are still detectable after more than 2 weeks in the majority of women receiving single-dose nevirapine - Implications for intervention studies
ABSTRACT Single-dose nevirapine is a highly cost-effective strategy to reduce perinatal HIV-1 transmission. Its major disadvantage is the selection of nevirapine resistance in 20% to 30% of women, probably attributable to the long elimination half-life of nevirapine. To develop intervention strategies, it is important to know the interpatient variability in nevirapine half-life in women receiving a single dose of nevirapine.
HIV-negative, healthy, nonpregnant Dutch women were eligible for this study. After administration of a single 200-mg dose of nevirapine to the subjects, blood was sampled for measurement of nevirapine twice a week for a total of 21 days. Nevirapine plasma levels were determined by a validated high-performance liquid chromatography method with a lower limit of quantification of 0.15 mg/L. The primary end point was the first sample with an undetectable nevirapine concentration.
Forty-four subjects participated. The median age, height, and body weight (interquartile range) were 26 (21-33) years, 1.72 (1.68-1.75) m, and 64 (59-75) kg, respectively. The median elimination half-life of nevirapine was 56.7 hours, with a range of 25.6 to 164 hours. The time to the first undetectable nevirapine plasma concentration was 10 days in 4 subjects, 14 days in 12 subjects, 17 days in 12 subjects, and 21 days in 9 subjects. In the remaining 7 subjects, nevirapine was still detectable on day 21, the last day of sampling. Time to an undetectable nevirapine plasma concentration was influenced by oral contraceptive use but not by age, height, body weight, body surface area, alcohol use, or smoking.
Most women who received a single 200-mg nevirapine dose still had detectable plasma concentrations of nevirapine after more than 2 weeks. This information is valuable for designing intervention studies to prevent the development of nevirapine resistance.
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ABSTRACT: Thin layer chromatography (TLC) can be used to perform therapeutic drug monitoring in resource-limited settings, where more expensive analytical methods, such as high-performance liquid chromatography or liquid chromatography-mass spectrometry, are not feasible. The aim of this cross-sectional study was to compare saliva concentrations of nevirapine (NVP) with self-reported adherence in patients on NVP-containing antiretroviral treatment at Kilimanjaro Christian Medical Centre, Moshi, Tanzania. HIV-infected patients using a combination of zidovudine + lamivudine + NVP, or stavudine + lamivudine + NVP, for more than 4 weeks were included. Saliva samples were collected using dental cotton rolls impregnated with citric acid (20 mg). Saliva NVP concentrations were analyzed using TLC. Adherence to ARV medication was assessed by self-reporting using the Morisky scale. Of the 91 study participants, 79 (86.8%) had therapeutic saliva NVP concentrations (ie, >1.75 mg/L) and 12 (13.2%) had subtherapeutic concentrations. Self-reported adherence among the study participants was high in 62 participants (68.1%), moderate in 24 (26.4%), and low in 5 (5.5%). Fifty-seven (91.9%) of the study participants with high self-reported adherence had therapeutic saliva NVP concentrations. Of the 5 participants with low self-reported adherence, 3 had therapeutic NVP concentrations. A high proportion of patients had therapeutic NVP saliva concentrations as measured by TLC, which showed a good agreement with self-reported adherence.Therapeutic drug monitoring 12/2013; DOI:10.1097/FTD.0000000000000005 · 1.93 Impact Factor
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ABSTRACT: Objective. Nevirapine is metabolized by cytochrome P450 (CYP) 2B6 and CYP3A4, We characterized relationships between clinical parameters, human genetics, pharmacokinetics, and HIV-1 drug resistance mutations in pregnant women following single-dose intrapartum nevirapine.Methods. In AIDS Clinical Trials Group study A5207, women received nevirapine at onset of labor, and were randomized to lamivudine/zidovudine, emtricitabine/tenofovir, or lopinavir/ritonavir, for 7 or 21 days. Plasma nevirapine was quantified at post-partum day 1 and weeks 1, 3 and 5. We assayed 214 polymorphisms in CYP2B6 and other genes and evaluated associations with pharmacokinetic parameters included elimination constant, time to protein-adjusted 50% inhibitory concentration (IC50), and week 5 nevirapine below quantification limit.Results. Among 301 women with evaluable pharmacokinetic and genotype data, lower body mass index and randomization to lopinavir/ritonavir were associated with more rapid nevirapine elimination. Among those of African ancestry, longer time to IC50 was associated with CYP2B6 983T→C (p=0.004) but not with CYP2B6 516G→T (p=0.8). Among Indians, slower nevirapine elimination was associated with CYP2B6 516G→T (p=0.04). Emergent resistance was infrequent and not associated with pharmacokinetics or CYP2B6 genotype.Conclusions. Effects on plasma drug exposure following single-dose nevirapine may be greater for CYP2B6 983T→C than 516G→T, and are less pronounced than at steady state.The Journal of Infectious Diseases 05/2013; 208(4). DOI:10.1093/infdis/jit223 · 5.78 Impact Factor
JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2014; 65(2):e90-4. DOI:10.1097/QAI.0b013e3182a2db02 · 4.39 Impact Factor