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Nevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub-Saharan African women.
- Source :
-
AIDS (London, England) [AIDS] 2012 Apr 24; Vol. 26 (7), pp. 833-41. - Publication Year :
- 2012
-
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.<br />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.<br />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.<br />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).<br />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.
- Subjects :
- Adult
Africa South of the Sahara
CD4 Lymphocyte Count
Drug Therapy, Combination
Female
Humans
Nevirapine adverse effects
Nevirapine blood
Reverse Transcriptase Inhibitors adverse effects
Reverse Transcriptase Inhibitors blood
Risk Factors
Treatment Outcome
Chemical and Drug Induced Liver Injury etiology
Exanthema chemically induced
HIV Infections drug therapy
Nevirapine pharmacokinetics
Reverse Transcriptase Inhibitors pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5571
- Volume :
- 26
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 22301417
- Full Text :
- https://doi.org/10.1097/QAD.0b013e328351a521