HIV Treatment Bulletin - Vol. 7, No. 6, June 2006
Polly Clayden, HIV i-Base

Several studies have reported the development of resistance to nevirapine even after taking a single dose of the drug, which is commonly used in the resource-limited setting for the prevention of mother to child transmission. This is likely due to the long half-life of nevirapine that results in the drug being found in blood for many days after taking the one dose.

A poster from Rafaella L’homme and coworkers from the Radboud University Nijmegen Medical Centre presented findings from a study exploring the novel strategy of using enzyme inducers to reduce nevirapine half-life and thereby reduce the risk of developing resistance.

This small study evaluated the use of several different strategies including using carbamazepine, phenobarbital, phenytoin, St. John’s Wort tea, retinyl palmitate and beta-carotene, and cholecalciferol.

This was a phase-I single-centre, open-label, two period, nine-group, PK study. A single 200 mg dose of nevirapine was administered to 36 HIV negative non-pregnant women in both period 1 and 2, blood samples were taken twice weekly for 21 days. In period 2 additional interventions (single dose carbamazepine, phenobarbital or phenytoin; phenytoin for 3 or 7 days; St Johns Wort, vitamin A or cholecalciferol for 14 days) were administered to all participants except for the control group. The primary end point was the ratio of nevirapine half-life in period 2 to nevirapine half-life in period 1.

Three of the interventions resulted in the half-life of nevirapine being significantly reduced. These included a single 400mg dose of carbamazepine (p=0.002), once a day 184mg phenytoin for three days (p=0.001) and once a day 184mg phenytoin for seven days (p=0.002). The half-life of nevirapine was reduced by 35.3%, 38.2% and 35.9% respectively. This resulted in a 4.5 – 8.8 day reduction in time to when nevirapine could not be detected in blood. The other five interventions had no effect on the nevirapine half-life.

These interventions now need to be studied in the real world setting to determine if this will lead to a decreased risk of developing resistance to nevirapine among pregnant women taking single dose nevirapine to prevent HIV transmission to their newborns.

Ref: L’homme R, Dijkema T, A. van der Ven A et al. Enzyme inducers reduce nevirapine half-life. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 5.

2006-06-10
IB060706-12

©2006. I-BASE HIV Treatment Bulletin. Permission to reproduce courtesy of HIV i-Base, Third Floor East, Thrale House, 44-46 Southwark Street, London SE1 1UN - T: +44 (0) 20 7407 8488 F: +44 (0) 20 7407 8489

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2006. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2006. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content.