891    

Background: NVP in a single 200-mg dose is a highly cost-effective strategy to reduce perinatal HIV-1 transmission. Its major disadvantage is the selection of NVP resistance in 20 to 30% of women, probably due to the long elimination half-life of NVP. In order to develop intervention strategies it is of crucial importance to know the interpatient variability in NVP half-life in women receiving a single dose of NVP, and factors that may influence this.

Methods:  HIV-negative, healthy, non-pregnant Dutch women were eligible for this study which was conducted as a prelude to a subsequent study in Tanzania. After receiving a single 200-mg dose of NVP (day 1), blood was sampled for measurement of NVP twice-a-week for a total of 21 days. NVP plasma levels were determined by a validated HPLC method with a lower limit of quantification of 0.15 mg/L. The primary endpoint was the first sample with an undetectable NVP concentration.

Results: For 44 participants, the median age, height, and body weight (+ interquartile range) were:  26 (21 to 33) years, 1.72 (1.68 to 1.75) m, and 64 (59 to 75) kg, respectively. Median elimination half-life of NVP was 56.7 hours with a range of 25.6 to 164 hours. The time to the first undetectable NVP plasma concentration was 11 days in 4 subjects, 15 days in 12, 18 days in 12, and 21 days in 9 subjects. In the remaining 7 subjects NVP was still detectable on day 22, the last day of sampling. Time to an undetectable NVP plasma concentration was not influenced by age, height, body weight, body surface area, alcohol use or smoking.

Conclusions: The majority of women who received a single NVP dose of 200 mg still had detectable plasma concentrations of NVP after more than 2 weeks. This information, if confirmed in the African setting, is valuable for designing intervention studies to prevent the development of NVP resistance.

Keywords: nevirapine; pharmacokinetics; mother-to-child transmission