Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis

Background: Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. Methods: HIV-1–infected patients with CD4+ T-lymphocyte count #100 cells per microliter and TB diagnosis received standard anti- TB therapy and a fixed-dose combination of stavudine, lamivudine, and NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy. Results: In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 mgmL21h21; P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 mgmL21h21; P = 0.17). The median Ctrough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 mg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 mg/mL; P = 0.17). The proportion of subjects with Ctrough values #3 mg/mL was 31.2% (5 of 16), 40.0% (6 of 15), and 7.7% (1 of 13) at T1, T2, and T3, respectively. Conclusions: The reduction of the area under the curve of NVP during concomitant RFM treatment substantially decreases over time.