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Clinical Trial
. 2012 Apr 24;26(7):833-41.
doi: 10.1097/QAD.0b013e328351a521.

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

Betty J Dong  1 , Yu Zheng, Michael D Hughes, Adam Frymoyer, Davide Verotta, Patricia Lizak, Frederick Sawe, Judith S Currier, Shahin Lockman, Francesca T Aweeka; AIDS Clinical Trials Group Study 5208 Team
Affiliations
Clinical Trial

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

Betty J Dong et al. AIDS. .

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.

Trial registration: ClinicalTrials.gov NCT00089505.

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Figures

Figure 1a and 1b
Figure 1a and 1b
Kaplan–Meier plot for proportion of women experiencing rash and liver related events over time from starting NVP-based therapy.
See this image and copyright information in PMC

References

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