Low nevirapine plasma concentrations predict virological failure in an unselected HIV-1-infected population

Objective: To assess the relationship between plasma nevirapine concentrations and plasma HIV-1 RNA response in HIV-1-infected patients. Design: An observational cohort analysis. Methods: Plasma samples were obtained on a routine basis from 189 patients receiving nevirapine 200mg twice daily, and plasma nevirapine concentrations were measured with reversed phase high performance liquid chromatography. Patients were divided into two groups based on plasma nevirapine concentrations below (and equal to) or above 3 mg/L. The association between steady-state nevirapine concentrations and plasma HIV-1 RNA was determined by multivariate analysis. Results: Out of 189 patients, 13 (7%) had low nevirapine plasma concentrations and 176 patients had concentrations above 3 mg/L. In total, 22 (12%) patients showed virological failure and 8 patients (4%) discontinued nevirapine because of adverse effects. The risk of failure in patients with nevirapine plasma concentrations ≤3mg/L was increased (relative risk 5.0, 95% CI 1.8-13.7). Rashes and liver enzyme elevations each occurred in 8% of patients. Conclusion: Low nevirapine drug concentrations are predictive of virological failure.