Comparison of nevirapine plasma concentrations between lead-in and steady-state periods in Chinese HIV-infected patients

Abstract

Objectives: To investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations.

Methods: 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.

Results: 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 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).

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00872417.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow chart of participants through the clinical trial.

ART: antiretroviral therapy; AZT: zidovudine; NVP: nevirapine; 3TC: lamivudine; D4T: stavudine; Ctrough: trough concentrations of nevirapine; Cmax: peak concentrations of nevirapine.

Figure 2. Comparison of nevirapine plasma concentrations between lead-in and steady-state periods during follow-up 48 weeks.

The differences between lead-in and steady-state periods for nevirapine (A) trough (P<0.0001) and (B) peak (P<0.0001) concentrations were assessed by the Kruskal-Wallis H test.

Figure 3. Comparison of nevirapine trough concentration in 105 patients with HIV infection.

Analysis of variance was utilized to evaluate nevirapine trough concentration in 105 HIV+ patients with 6 consecutive points during follow-up 48 weeks (P<0.05).

Figure 4. Relationship between nevirapine trough concentration and baseline liver function.

The nevirapine trough concentration at week 2 in patients with baseline ALT level P = 0.045). No significant difference was observed between lead-in and steady-state periods in patients with (A) ALT level ≥1.5×ULN (P = 0.171) and (B) AST level ≥1.5×ULN (P = 0.769) at baseline.

Figure 5. Relationship between nevirapine trough concentration and underlying liver diseases.

The differences for nevirapine trough concentration between lead-in and steady-state periods was observed in patients with HBV infection (A). The nevirapine trough concentration at week 4 was significantly lower than the values at week 24, 36 and 48 (P<0.05) in patients with HCV infection (B). The nevirapine trough concentration at week 48 in patients with HCV infection was significant higher than those without HCV coinfection (P = 0.004).