Short Communication: Changes in Nevirapine Plasma Concentrations Over Time and Its Relationship with Liver Enzyme Elevations

Abstract
Liver enzyme elevations are frequently seen in patients treated with nevirapine (NVP). Both elevated NVP plasma levels and hepatitis C virus (HCV) infection seem to favor the development of NVP-related liver toxicity. We have examined variation on NVP Ctrough over time, as well as the impact of NVP Ctrough concentrations and the role of chronic hepatitis C on the incidence of liver enzyme elevations over a 48-week study period in HIV-infected patients on NVP therapy. Thirty-seven patients who initiated a triple regimen of NVP (200 mg bid) plus two nucleoside reverse transcriptase inhibitors (NRTI) were analyzed. A significant increase in serum transaminase levels occurred progressively over time. However, no significant variations in NVP plasma Ctrough were noticed in 48 weeks. In total population, maximum fold increase (MFI) in serum AST, ALT, and GGT was correlated with 24 week NVP Ctrough. In HCV+ subjects, 12-week NVP Ctrough was closely correlated with maximum transaminase elevations, whereas in HCV patients, 24-week concentrations were correlated with maximum transaminase increase. However, no differences in either NVP plasma Ctrough or in MFI in transaminase levels could be determined when comparing patients with and without hepatitis C at any time point.