Nevirapine Levels after Discontinuation of Rifampicin Therapy and 60‐Week Efficacy of Nevirapine‐Based Antiretroviral Therapy in HIV‐Infected Patients with Tuberculosis

Abstract

Seventy patients with human immunodeficiency virus (HIV) and tuberculosis coinfection who initiated nevirapine-based antiretroviral therapy and had trough nevirapine levels determined while receiving rifampicin were enrolled in a study. After discontinuation of rifampicin therapy, mean nevirapine levels (+/- standard deviation) increased from 5.4+/-3.5 mg/L to 6.4+/-3.4 mg/L (P=.047), but no nevirapine-related adverse events occurred. There was no statistically significant difference in 60-week antiviral efficacy between these patients and patients receiving nevirapine-based antiretroviral therapy alone (P>.05).

Effect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis

“…Two adequately powered Thai studies conducted in patients with TB reported reductions of nevirapine trough concentrations of 15.6% 18 and 37.2%, 8 which are similar to the 26.3% that we found. However, the mean trough nevirapine concentrations with concomitant rifampicin-based antitubercular therapy in the Thai studies were 5.5 and 5.4 mg/L, 8,18 considerably higher than the 3.2 mg/L that we found.…”

“…However, the mean trough nevirapine concentrations with concomitant rifampicin-based antitubercular therapy in the Thai studies were 5.5 and 5.4 mg/L, 8,18 considerably higher than the 3.2 mg/L that we found. The likely explanation for the higher nevirapine trough concentrations is their lower body weight (10 kg lower than our patients' mean weight of 65.8 kg), given that nevirapine clearance is similar in Thai and South African patients.…”

“…19 A Thai cohort study of 70 patients on nevirapine-based combination ART and concomitant rifampicinbased antitubercular therapy found that virological suppression was similar to a control group, 7 with virological suppression rates remaining similar up to 60 weeks. 18 However, as mentioned above, Thai patients have lower body weight and higher trough nevirapine concentrations.…”

Population pharmacokinetics of nevirapine in combination with rifampicin-based short course chemotherapy in HIV- and tuberculosis-infected South African patients

“…In another study on 70 Thai patients coinfected with HIV and TB, rifampicin reduced the nevirapine C min by 17%, but more than 70% of the patients had concentrations above 3.4 mg/L [13]. These patients were followed after the discontinuation of rifampicin, and their C min increased by 16.7% [14].…”

“…The mutation is observed after 4 weeks of monotherapy and may occur in just 2 weeks if viral replication is not well controlled in the presence of nevirapine [4]. Several reports on the effect of rifampicin on nevirapine pharmacokinetics have been published [4,[9][10][11][12][13][14]. However, to our knowledge this is the first modelling report on the effect of rifampicin on nevirapine pharmacokinetics in South African patients.…”