Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention.
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Author list: Podany AT, Leon-Cruz J, Hakim J, Supparatpinyo K, Omoz-Oarhe A, Langat D, Mwelase N, Kanyama C, Gupta A, Benson CA, Chaisson RE, Swindells S, Fletcher CV, AIDS Clinical Trials Group A5279 Team
Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option B
Publication year: 2020
Journal: Journal of Antimicrobial Chemotherapy (0305-7453)
Journal acronym: J Antimicrob Chemother
ISSN: 0305-7453
eISSN: 1460-2091
Languages: English-Great Britain (EN-GB)
Abstract
BACKGROUND\nOBJECTIVES\nMETHODS\nRESULTS\nCONCLUSIONS\nThe use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART.\nTo evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV.\nParticipants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated.\nSeventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33).\nThe CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.
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