Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention

A. T. Podany, J. Leon-Cruz, J. Hakim, K. Supparatpinyo, A. Omoz-Oarhe, D. Langat, N. Mwelase, C. Kanyama, A. Gupta, C. A. Benson, R. E. Chaisson, S. Swindells, C. V. Fletcher, Peter Kim, Daniel Johnson, Laura Moran, Janet Andersen, Yajing Bao, Shirley Wu, Christina Blanchard-HoranAnn Walawander, Katherine Shin, Ruth Ebiasah, David Holland, Marc Antoine Jeanjuste, Eric Nuermberger, Sandy Pillay, Ian Sanne, Janet Nicotera, David Shugarts, Amina Shali, Jimi Tutko, Brigitte Demers, Marilyn Maroni, Jorge L. Sanchez, David Iglesias, Javier Lama, Mitch Matoga, Guilherme Do Amaral Calvet, Ronald Kibet Tonui, Taolo Modise, Margaret Kasaro, Kogieleum Naidoo, Deelip Kadam, William Burman

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Background: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. Objectives: To 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. Methods: Participants 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. Results: Seventy-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). Conclusions: The 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.

Original languageEnglish (US)
Pages (from-to)718-721
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume76
Issue number3
DOIs
StatePublished - Mar 1 2021

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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