HIV/TB coinfected patients (n=28) initiating an efavirenz (600 mg once daily) containing regimen were randomized to receive daily rifapentine (1200 mg), isoniazid, pyrazinamide and either ethambutol or moxifloxacin.  Efavirenz plasma concentration were measured 4 and 8 weeks after efavirenz initiation and after TB treatment completion. Efavirenz apparent oral clearance (CL/F) was modelled using Bayesian estimation; population PK priors were taken from previous efavirenz PK studies.  Median (IQR) efavirenz concentration 4 and 8 weeks post efavirenz initiation were 2.76 (2.12-4.67) mg/L and 2.86 (2.19-4.88) mg/L, respectively. Efavirenz concentrations measured after TB treatment completion were 2.86 (1.93-4.21) mg/L. The number of participants with efavirenz concentrations >1 mg/L at 4 and 8 weeks post efavirenz initiation were 89% and 93% respectively. 90% of participants had efavirenz concentrations >1 mg/L post TB treatment. Median (IQR) efavirenz CL/F were 7.28 (5.47-10.08) and 8.3 (6.17-10.66) L/h during and post TB treatment. The GMR (90% CI) of during to post TB efavirenz CL/F was 0.89 (0.64-1.23). The CL/F of efavirenz decreased slightly during 17 weeks of daily TB treatment as compared to post-TB treatment. The proportion of participants with efavirenz concentrations <1mg/L did not cross below the pre-specified threshold of 20%. 20/23 participants had undetectable HIV-1 RNA at completion of TB treatment. These data support the initiation of efavirenz containing regimens during co-administration of daily high-dose rifapentine for TB treatment.

Coadministration of efavirenz and rifapentine was studied in 87 HIV/TB coinfected subjects stable on efavirenz-containing ART who started rifapentine containing TB treatment. Rifapentine dosing was based on body weight (30–34.9 kg, 300 mg once daily; 35–44.9 kg, 450 mg once daily; ≥45 kg, 600 mg once daily). Median efavirenz apparent oral clearance increased by ~4% during rifapentine treatment. The proportion of participants with midinterval efavirenz concentrations ≥1 mg/L did not cross below the prespecified threshold of >80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression.