TY - JOUR
T1 - Efavirenz Pharmacokinetics and Human Immunodeficiency Virus Type 1 (HIV-1) Viral Suppression Among Patients Receiving Tuberculosis Treatment Containing Daily High-Dose Rifapentine
AU - Podany, Anthony T.
AU - Pham, Michelle
AU - Sizemore, Erin
AU - Martinson, Neil
AU - Samaneka, Wadzanai
AU - Mohapi, Lerato
AU - Badal-Faesen, Sharlaa
AU - Dawson, Rod
AU - Johnson, John L.
AU - Mayanja, Harriet
AU - Lalloo, Umesh
AU - Whitworth, William C.
AU - Pettit, April
AU - Campbell, Kayla
AU - Phillips, Patrick P.J.
AU - Bryant, Kia
AU - Scott, Nigel
AU - Vernon, Andrew
AU - Kurbatova, Ekaterina V.
AU - Chaisson, Richard E.
AU - Dorman, Susan E.
AU - Nahid, Payam
AU - Swindells, Susan
AU - Dooley, Kelly E.
AU - Fletcher, Courtney V.
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2022/8/15
Y1 - 2022/8/15
N2 - 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.
AB - 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.
KW - HIV/AIDS
KW - efavirenz
KW - pharmacokinetics
KW - rifapentine
KW - tuberculosis
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U2 - 10.1093/cid/ciab1037
DO - 10.1093/cid/ciab1037
M3 - Article
C2 - 34918028
AN - SCOPUS:85138126832
SN - 1058-4838
VL - 75
SP - 560
EP - 566
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -