Pharmacokinetics and 48-Week Efficacy of Nevirapine: 400 mg Versus 600 mg per day in HIV–Tuberculosis Coinfection Receiving Rifampicin

Abstract

Background

We aim here to determine the appropriate dose of nevirapine (NVP) in Thai HIV–tuberculosis (TB)-coinfected patients receiving rifampicin.

Methods

Thirty-two HIV-infected adults with CD4⁺ T-cell counts <200 cells/mm³ and active TB, receiving rifampicin for 2–6 weeks were randomized to receive either NVP 400 mg (NVP₄₀₀) or 600 mg (NVP₆₀₀) per day plus two nucleoside reverse transcriptase inhibitors; a 2-week NVP lead-in was performed at 200 mg once daily (OD) and 200 mg twice daily, respectively. Plasma NVP levels were determined at weeks 2, 4 and 12. Twelve-hour pharmacokinetics (PK) were obtained (n=20) at week 4.

Results

Baseline body weight was comparable. There were more patients with NVP plasma concentration at 12 h (C₁₂) <3.1 mg/l at week 2 in NVP₄₀₀ than in NVP₆₀₀ (79% versus 19%, respectively; P=0.002). However, the proportions were comparable at weeks 4 and 12. From week 4, 12 h PK studies showed that NVP₄₀₀ had lower median NVP area under the plasma concentration-0–12 h (AUC_{0–12 h}), maximum concentration in plasma (C_max) and C₁₂ than NVP₆₀₀ (P<0.05). Four patients in NVP₆₀₀ developed NVP hypersensitivity. At week 48, the median CD4⁺ T-cell count rise and proportion with viral load <50 copies/ml (intention-to-treat analysis 56% versus 50% and as-treated analysis 75% versus 89%) were comparable.

Conclusions

In rifampicin-treated patients, 200 mg NVP OD lead-in led to a significant short-term suboptimal NVP C₁₂ level, while NVP 400 mg lead-in then 600 mg/day was associated with a high rate of NVP hypersensitivity. Forty-eight week efficacy was comparable. Thus, NVP 600 mg/day in rifampicin-treated patients is not recommended.