Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine
| العنوان: | Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine |
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| المؤلفون: | Anthony T Podany, Michelle Pham, Erin Sizemore, Neil Martinson, Wadzanai Samaneka, Lerato Mohapi, Sharlaa Badal-Faesen, Rod Dawson, John L Johnson, Harriet Mayanja, Umesh Lalloo, William C Whitworth, April Pettit, Kayla Campbell, Patrick P J Phillips, Kia Bryant, Nigel Scott, Andrew Vernon, Ekaterina V Kurbatova, Richard E Chaisson, Susan E Dorman, Payam Nahid, Susan Swindells, Kelly E Dooley, Courtney V Fletcher |
| المصدر: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol 75, iss 4 Clin Infect Dis |
| بيانات النشر: | eScholarship, University of California, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Microbiology (medical), Cyclopropanes, Anti-HIV Agents, Moxifloxacin, Clinical Trials and Supportive Activities, Antitubercular Agents, HIV Infections, Medical and Health Sciences, Microbiology, Rare Diseases, Clinical Research, Major Article, Humans, Tuberculosis, Evaluation of treatments and therapeutic interventions, HIV, efavirenz, Biological Sciences, Benzoxazines, AIDS, rifapentine, Orphan Drug, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, Alkynes, 6.1 Pharmaceuticals, HIV-1, HIV/AIDS, Rifampin, Infection, pharmacokinetics |
| الوصف: | Background 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). Methods 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. Results 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%. Conclusions 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. Clinical Trials Registration NCT 02410772. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::17723c114dd6de4698d163d6fbb7ee29 https://escholarship.org/uc/item/4694p0w3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....17723c114dd6de4698d163d6fbb7ee29 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |