Journal article
A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006)
AIDS (London), Vol.13(4), pp.479-486
03/1999
DOI: 10.1097/00002030-199903110-00006
PMID: 10197376
Abstract
Objective: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life.
Design: An open label phase I/II study.
Setting: Tertiary care hospital, Kampala, Uganda.
Patients and interventions: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age.
Outcomes: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored.
Results: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age.
Conclusion: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.
Details
- Title: Subtitle
- A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006)
- Creators
- Philippa MusokeLaura A GuayDanstan BagendaMark MirochnickClemensia NakabiitoThomas FlemingTerry ElliottScott HortonKevin DransfieldJoseph W PavAmal MurarkaMelissa AllenMary Glenn FowlerLynne MofensonDavid HomFrancis MmiroJ. Brooks Jackson
- Resource Type
- Journal article
- Publication Details
- AIDS (London), Vol.13(4), pp.479-486
- DOI
- 10.1097/00002030-199903110-00006
- PMID
- 10197376
- ISSN
- 0269-9370
- eISSN
- 1473-5571
- Language
- English
- Date published
- 03/1999
- Academic Unit
- Pathology; VPMA - Administration
- Record Identifier
- 9984047702702771
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