Comparison of Nevirapine Plasma Concentrations between Lead-In and Steady-State Periods in Chinese HIV-Infected Patients

<div><h3>Objectives</h3><p>To investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations.</p> <h3>Methods</h3><p>This 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.</p> <h3>Results</h3><p>A 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 <em>v.s.</em> 4.86 µg/mL, for ALT <1.5×ULN and ≥1.5×ULN, respectively, <em>P</em> = 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 (<em>P</em> = 0.171, <em>P</em> = 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 <em>v.s.</em> 6.15 µg/mL, <em>P</em> = 0.004).</p> <h3>Conclusions</h3><p>The 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.</p> <h3>Registration</h3><p>Clinicaltrial.gov ID: <a href="http://clinicaltrials.gov/ct2/show/NCT00872417">NCT00872417</a></p>