Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine

• Published in: Clinical infectious diseases 2022-09, Vol.75 (4), p.560-566
• Main Authors: Podany, Anthony T, Pham, Michelle, Sizemore, Erin, Martinson, Neil, Samaneka, Wadzanai, Mohapi, Lerato, Badal-Faesen, Sharlaa, Dawson, Rod, Johnson, John L, Mayanja, Harriet, Lalloo, Umesh, Whitworth, William C, Pettit, April, Campbell, Kayla, Phillips, Patrick P J, Bryant, Kia, Scott, Nigel, Vernon, Andrew, Kurbatova, Ekaterina V, Chaisson, Richard E, Dorman, Susan E, Nahid, Payam, Swindells, Susan, Dooley, Kelly E, Fletcher, Courtney V
• Format: Article
• Language: English
• Subjects: Alkynes; Anti-HIV Agents; Antitubercular Agents; Benzoxazines; Cyclopropanes; HIV Infections - drug therapy; HIV-1; Humans; Major; Moxifloxacin - therapeutic use; Rifampin - analogs & derivatives; Tuberculosis - complications; Tuberculosis - drug therapy
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/ciab1037

A 4-month regimen containing rifapentine and moxifloxacin has noninferior efficacy compared to the standard 6-month regimen for drug-sensitive tuberculosis. We evaluated the effect of regimens containing daily, high-dose rifapentine on efavirenz pharmacokinetics and viral suppression in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB). In the context of a Phase 3 randomized controlled trial, HIV-positive individuals already virally suppressed on efavirenz--containing antiretroviral therapy (ART) (EFV1), or newly initiating efavirenz (EFV2) received TB treatment containing rifapentine (1200 mg), isoniazid, pyrazinamide, and either ethambutol or moxifloxacin. Mid-interval efavirenz concentrations were measured (a) during ART and TB cotreatment (Weeks 4, 8, 12, and 17, different by EFV group) and (b) when ART was taken alone (pre- or post-TB treatment, Weeks 0 and 22). Apparent oral clearance (CL/F) was estimated and compared. Target mid-interval efavirenz concentrations were > 1 mg/L. Co-treatment was considered acceptable if > 80% of participants had mid-interval efavirenz concentrations meeting this target. EFV1 and EFV2 included 70 and 41 evaluable participants, respectively. The geometric mean ratio comparing efavirenz CL/F with vs without TB drugs was 0.79 (90% confidence interval [CI] .72-.85) in EFV1 and 0.84 [90% CI .69-.97] in EFV2. The percent of participants with mid-interval efavirenz concentrations > 1mg/L in EFV1 at Weeks 0, 4, 8, and 17 was 96%, 96%, 88%, and 89%, respectively. In EFV2, at approximately 4 and 8 weeks post efavirenz initiation, the value was 98%. TB treatment containing high-dose daily rifapentine modestly decreased (rather than increased) efavirenz clearance and therapeutic targets were met supporting the use of efavirenz with these regimens, without dose adjustment. NCT02410772.