Effect of High-Dose Rifapentine on Efavirenz Pharmacokinetics in HIV, Tuberculosis Coinfection

Researchers conducted a study to assess the effect of high-dose rifapentine on the pharmacokinetics of efavirenz in patients with HIV and tuberculosis coinfection receiving efavirenz-based antiretroviral therapy.

Results of a phase 3 randomized trial found that daily treatment with high-dose rifapentine for tuberculosis (TB) infection decreased efavirenz clearance and achieved therapeutic targets among among patients coinfected with HIV receiving efavirenz-based antiretroviral therapy (ART). These findings were published in Clinical Infectious Diseases.

This study was an international, multicenter, open-label, phase 3, randomized controlled trial that enrolled patients with either tuberculosis or HIV and TB coinfection. Patients with TB infection were stratified by site, lung cavitation, and HIV status and were randomly assigned in a 1:1:1 fashion to receive either a 4-month regimen of high-dose rifapentine (1200 mg), isoniazid, weight-based pyrazinamide, and weight-based ethambutol; a 4-month regimen of high-dose rifapentine, isoniazid, pyrazinamide, and moxifloxacin; or a 6-month regimen of efavirenz plus 2 nucleoside reverse transcriptase inhibitors. To evaluate the pharmacokinetics (PK) of efavirenz-based ART, the researchers performed a subgroup analysis among patients who were either virally suppressed on efavirenz-based ART (EFV1; n=70) or had recently initiated efavirenz-based ART (EFV2; n=41). Patients included in the subgroup analysis were randomly assigned to 1 of the 4-month treatment arms. The primary outcome was the proportion of patients who maintained mid-interval efavirenz plasma concentrations greater than or equal to 1 mg/L at least twice during the course of treatment

Among patients in the EFV1 and EFV2 cohorts, 55.7% and 65.9% were men, the mean age was 41 (IQR, 36-48) and 37 (IQR, 30-43) years, and 94.3% and 90.2% were Black, respectively. Further analysis between patients in the EFV1 and EFV2 cohorts showed that the median CD4+ cell count was 355 (IQR, 227-446) and 331 (IQR, 210-410) cells/mL3, the median HIV RNA viral load was 54 (IQR, 20-123) and 221,548 (IQR, 714-1,200,684) copies/mL, and 30% and 20% had previously been treated for TB infection, respectively.

Among patients included in the EFV1 cohort, the median mid-interval plasma concentrations of efavirenz were 2.41, 2.99, 2.71, and 2.45 mg/L at weeks 0, 4, 8, and 17, respectively. Patients in the EFV2 cohort had median mid-interval plasma concentrations of efavirenz of 2.98, 2.74, 3.04, 3.17, and 2.99 mg/L at weeks 4, 8, 12, 17, and 22, respectively. Throughout the study, the proportion of patients with plasma efavirenz concentrations greater than1 mg/L ranged between 88% and 96% among those in the EFV1 cohort and between 90% and 100% among those in the EFV2 cohort..

At weeks 17 and 22, 98% of patients in the EFV1 cohort had HIV RNA viral loads greater than 50 copies/mL. Of note, 1 patient in the EFV1 cohort had a significantly increased HIV RNA viral load (365 copies/mL) at week 17. In regard to patients in the EFV2 cohort, although 95% had an undetectable HIV RNA viral load at week 17, there were 2 patients with HIV RNA viral loads of 79 and 85 copies/mL at week 22, respectively.

This study was limited by the exclusion of integrase strand transfer inhibitor-based ART regimens and the large number of patients with either efavirenz concentrations below the level of quantitation or incomplete PK data.

According to the researchers, “The PK, safety, and virologic data described herein provide important support for” the use of high-dose rifapentine in patients with HIV and TB coinfection receiving efavirenz-based ART.

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Podany AT, Pham M, Sizemore E, et al. Efavirenz pharmacokinetics and HIV-1 viral suppression among patients receiving TB treatment containing daily high-dose rifapentine. Clin Infect Dis. 2021;ciab1037. doi:10.1093/cid/ciab1037