Abstract
ObjectivesTo investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations.MethodsThis was a prospective, multicentre cohort study with 532 HIV-infected patients receiving nevirapine as a part of their initial antiretroviral therapy. Plasma samples were collected at trough or peak time at the end of week 2 (lead-in period) and week 4, 12, 24, 36, and 48 (steady-state period), and nevirapine concentrations were determined using a validated HPLC method. Potential influencing factors associated with nevirapine concentrations were evaluated using univariate and multivariate logistic regression.ResultsA total of 2348 nevirapine plasma concentrations were collected, including 1510 trough and 838 peak values. The median nevirapine trough and peak concentration during the lead-in period were 4.26 µg/mL (IQR 3.05–5.61) and 5.07 µg/mL (IQR 3.92–6.44) respectively, which both exceeded the recommended thresholds of nevirapine plasma concentrations. Baseline hepatic function had a moderate effect on median nevirapine trough concentrations at week 2 (4.25 µg/mL v.s. 4.86 µg/mL, for ALT <1.5×ULN and ≥1.5×ULN, respectively, P = 0.045). No significant difference was observed in median nevirapine trough concentration between lead-in and steady-state periods in patients with baseline ALT and AST level ≥1.5×ULN (P = 0.171, P = 0.769), which was different from the patients with ALT/AST level <1.5ULN. The median trough concentrations were significantly higher in HIV/HCV co-infected patients than those without HCV at week 48 (8.16 µg/mL v.s. 6.15 µg/mL, P = 0.004).ConclusionsThe 200 mg once-daily regimen of nevirapine might be comparable to twice-daily in plasma pharmacokinetics in Chinese population. Hepatic function prior to nevirapine treatment and HIV/HCV coinfection were significantly associated with nevirapine concentrations.RegistrationClinicaltrial.gov ID: NCT00872417
Highlights
Nevirapine is a human immunodeficiency virus type 1 (HIV-1) specific non-nucleoside reverse transcriptase inhibitor that binds directly to the viral reverse transcriptase of HIV-1 to block polymerase activity by causing disruption of the enzymes catalytic site [1]
The substantial benefits conferred by Combination antiretroviral therapy (cART), require strict patient adherence to the prescribed medication because poor adherence will lead to virologic failure
Comparison of nevirapine trough concentrations A total of 1510 nevirapine Ctrough were available during the 48
Summary
Nevirapine is a human immunodeficiency virus type 1 (HIV-1) specific non-nucleoside reverse transcriptase inhibitor that binds directly to the viral reverse transcriptase of HIV-1 to block polymerase activity by causing disruption of the enzymes catalytic site [1]. Nevirapine is frequently used as a part of first-line regimens for the management of treatment-naive patients in resource-limited countries. It is typically dosed at 200 mg once daily during the first 2 weeks (lead-in period) and 200 mg twice daily thereafter (steady-state period), due to metabolic autoinduction of cytochrome P450 isoenzymes [1]. Because high nevirapine concentrations are associated with increased adverse events [6,7,8,9,10,11,12] and low plasma concentration may lead to virologic failure and drug resistance [13,14], adoption of once-daily dosing regimen in clinical practice remains controversial
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