Nevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub-Saharan African women.

TitleNevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub-Saharan African women.
Publication TypeJournal Article
Year of Publication2012
AuthorsDong BJ, Zheng Y, Hughes MD, Frymoyer A, Verotta D, Lizak P, Sawe F, Currier JS, Lockman S, Aweeka FT
Corporate AuthorsAIDS Clinical Trials Group Study 5208 Team
JournalAIDS
Volume26
Issue7
Pagination833-41
Date Published2012 Apr 24
ISSN1473-5571
KeywordsAdult, Africa South of the Sahara, CD4 Lymphocyte Count, Drug Therapy, Combination, Drug-Induced Liver Injury, Exanthema, Female, HIV Infections, Humans, Nevirapine, Reverse Transcriptase Inhibitors, Risk Factors, Treatment Outcome
Abstract

OBJECTIVES: To estimate nevirapine (NVP) pharmacokinetics and examine its association with rash and/or hepatotoxicity in women starting antiretroviral treatment in the AIDS Clinical Trials Group A5208/OCTANE study in Africa.

DESIGN: In HIV-infected, nonpregnant women with screening CD4 cell count less than 200 cells/μl randomized to NVP (twice daily, after 14-day once-daily lead-in period) and tenofovir/emtricitabine, single NVP blood samples were collected 14 and 28 days following randomization. Rash and hepatotoxicity that occurred during therapy, or within 7 days after the last dose of NVP, were defined as toxicity.

METHODS: NVP pharmacokinetics were modeled by population pharmacokinetic analysis. Individual Bayesian pharmacokinetic estimates were used to calculate clearance, 24-h area under the curve, and predicted plasma concentrations.

RESULTS: Median week 4 NVP clearance was 2 l/h. Among the 359 women, 194 (54%) developed a rash of any grade; 82 (23%) had grade 2+ and nine (3%) had grade 3+ rash. Median clearance was 1.7 l/h for participants exhibiting 3+ rash versus 2 l/h in women without 3+ rash (P = 0.046). The odds of developing 3+ rash was 50% higher for every 20% decrease in clearance (P = 0.046). NVP discontinuation due to rash/liver toxicity was significantly more common among women with pretreatment CD4 cell count more than 250 cells/μl (P = 0.003).

CONCLUSION: In this study, HIV-infected African women starting a NVP-based antiretroviral regimen had a lower NVP clearance compared to previous reports. Severe rash, but not hepatotoxicity, was associated with higher NVP exposure. Albeit observed in a small number of women, baseline CD4 cell count at least 250 cells/μl was significantly associated with NVP toxicity.

DOI10.1097/QAD.0b013e328351a521
Alternate JournalAIDS
PubMed ID22301417
PubMed Central IDPMC3506024
Grant ListA1022763 / / PHS HHS / United States
A1068636 / / PHS HHS / United States
AI38838 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
GM26696 / GM / NIGMS NIH HHS / United States
K24 AI056933 / AI / NIAID NIH HHS / United States
K24 AI56933 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
R01 AI50587 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States