Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Clinical infectious diseases, 2022-09, Vol.75 (4), p.560-566

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.