A Randomized Trial Comparing Plasma Drug Concentrations and Efficacies between 2 Nonnucleoside Reverse-Transcriptase Inhibitor-Based Regimens in HIV-Infected Patients Receiving Rifampicin: The N2R Study

Background. To our knowledge, to date, no prospective, randomized, clinical trial has compared standard doses of efavirenz- and nevirapine-based antiretroviral therapy among patients with concurrent human immunodeficiency virus type 1 (HIV-1) infection and tuberculosis (TB) who are receiving rifampicin. Methods. Rifampicin recipients with concurrent HIV-1 infection and TB were randomized to receive antiretroviral therapy that included either efavirenz ( 600 mg per day) or nevirapine ( 400 mg per day). Efavirenz and nevirapine concentrations at 12 h after dosing ( C-12) were monitored at weeks 6 and 12. CD4(+) cell counts and HIV-1 RNA levels were assessed every 12 weeks. Results. One hundred forty-two patients were randomized into 2 groups equally. The mean body weight of patients was 53 kg, the mean CD4(+) cell count was 65 cells/mm(3), and the median HIV-1 RNA level was 5.8 log(10) copies/mL. At weeks 6 and 12, the mean C-12 of efavirenz (+/- standard deviation) were 4.27 +/- 4.49 and 3.54 +/- 3.78 mg/L, respectively, and those for nevirapine were and 5.59 +/- 3.48 mg/L and 5.6 +/- 2.65 mg/L, respectively. Interpatient variability in the efavirenz group was 2.3-fold greater than that in the nevirapine group (coefficient of variation, 107% vs. 47%). At week 12, 3.1% of patients in the efavirenz group and 21.3% in the nevirapine group had C-12 values that were less than the recommended minimum concentrations ( odds ratio, 8.396; 95% confidence interval, 1.808-38.993; P = .002). Intention-to-treat analysis revealed that 73.2% and 71.8% of patients in the efavirenz and nevirapine groups, respectively, achieved HIV-1 RNA levels <50 copies/mL at week 48, with respective mean CD4(+) cell counts of 274 and 252 cells/mm(3) (P > .05). Multivariate analysis revealed that patients with low C-12 values and those with a body weight <55 kg were 3.6 and 2.4 times more likely, respectively, to develop all-cause treatment failure (P < .05). Conclusions. Antiretroviral therapy regimens containing efavirenz ( 600 mg per day) were less compromised by concomitant use of rifampicin than were those that contained nevirapine ( 400 mg per day) in patients with concurrent HIV-1 infection and TB. Low drug exposure and low body weight are important predictive factors for treatment failure. Trial registration. ClinicalTrials.govidentifier:NCT00483054.