Population Pharmacokinetic Modeling and Simulation of Rifapentine Supports Concomitant Antiretroviral Therapy with Efavirenz and Non-Weight Based Dosing

Author:

Pham Michelle M.1,Podany Anthony T.1,Mwelase Noluthando2,Supparatpinyo Khuanchai3,Mohapi Lerato4,Gupta Amita5,Samaneka Wadzanai6,Omoz-Oarhe Ayotunde7,Langat Deborah8,Benson Constance A.9,Chaisson Richard E.10,Swindells Susan11,Fletcher Courtney V.111ORCID

Affiliation:

1. Antiviral Pharmacology Laboratory, UNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha, Nebraska, USA

2. University of the Witwatersrand Helen Joseph CRS, Johannesburg, South Africa

3. Chiang Mai University, Chiang Mai, Thailand

4. Soweto ACTG CRS, Perinatal HIV Research Unit, Johannesburg, South Africa

5. Johns Hopkins Hospital, Baltimore, Maryland, USA

6. Milton Park CRS, Harare, Zimbabwe

7. Molepolole Clinical Research Site, Molepolole, Botswana

8. Kenya Medical Research Institute/Walter Reed Project Clinical Research Center CRS, Kericho, Kenya

9. University of California San Diego, San Diego, California, USA

10. Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland, USA

11. Division of Infectious Diseases, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA

Abstract

The Brief Rifapentine–Isoniazid Efficacy for TB Prevention/A5279 trial demonstrated a 1-month daily regimen of rifapentine and isoniazid was noninferior to 9 months of isoniazid alone for preventing TB in persons living with HIV (PLWH). Our objective was to evaluate rifapentine pharmacokinetics in trial participants receiving antiretroviral therapy (ART) and perform simulations to compare weight-based rifapentine dosing with a standard, fixed dose.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference23 articles.

1. TB & HIV Coinfection. Basic TB Facts | TB | CDC. https://www.cdc.gov/tb/topic/basics/tbhivcoinfection.htm.

2. WHO. 2019.Tuberculosis and HIV. WHO. http://www.who.int/hiv/topics/tb/en/.

3. WHO. 2008. Three I’s meeting: intensified case finding (ICF), isoniazid preventive therapy (IPT), and TB infection control (IC) for people living with HIV.

4. Isoniazid preventive therapy for HIV-infected people: evidence to support implementation

5. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis

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