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Clinical Trial
. 2024 Oct 15;79(4):983-989.
doi: 10.1093/cid/ciae183.

Twice-Daily Dolutegravir-Based Antiretroviral Therapy With 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis Prevention

Anthony T Podany  1 , Yoninah Cramer  2 , Marjorie Imperial  3 , Susan L Rosenkranz  2 , Anchalee Avihingsanon  4 , Roberto Arduino  5 , Wadzanai Samaneka  6 , Irina Gelmanova  7 , Rada Savic  3 , Susan Swindells  8 , Rodney Dawson  9 , Anne F Luetkemeyer  10
Affiliations
Clinical Trial

Twice-Daily Dolutegravir-Based Antiretroviral Therapy With 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis Prevention

Anthony T Podany et al. Clin Infect Dis. .

Abstract

Background: One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashort option for tuberculosis prevention in people with human immunodeficiency virus (HIV). However, rifapentine may decrease antiretroviral drug concentrations and increase the risk of virologic failure. AIDS Clinical Trials Group A5372 evaluated the effect of 1HP on the pharmacokinetics of twice-daily dolutegravir.

Methods: A5372 was a multicenter, pharmacokinetic study in people with HIV (≥18 years) already on dolutegravir-containing antiretroviral therapy with HIV RNA <50 copies/mL. Participants received daily rifapentine/isoniazid (600 mg/300 mg) for 28 days as part of 1HP. Dolutegravir was increased to 50 mg twice daily during 1HP, and intensive pharmacokinetic sampling was performed on day 0 (before 1HP) and on the final day of 1HP treatment.

Results: Thirty-two participants (41% female; 66% Black/African; median [Q1, Q3] age, 42 [34, 49] years) were included in the pharmacokinetic analysis; 31 had HIV RNA <50 copies/mL at the end of 1HP dosing. One participant had an HIV RNA of 160 copies/mL at day 28, with HIV RNA <50 copies/mL upon repeat testing on day 42. The median (Q1, Q3) dolutegravir trough concentration was 1751 ng/mL (1195, 2542) on day 0 versus 1987 ng/mL (1331, 2278) on day 28 (day 28:day 0 geometric mean ratio, 1.05 [90% confidence interval, .93-1.2]; P = .43). No serious adverse events were reported.

Conclusions: Dolutegravir trough concentrations with 50 mg twice-daily dosing during 1HP treatment were greater than those with standard-dose dolutegravir once daily without 1HP. These pharmacokinetic, virologic, and safety data provide support for twice-daily dolutegravir use in combination with 1HP for tuberculosis prevention.

Clinical trials registration: NCT04272242.

Keywords: HIV/AIDS; pharmacodynamics; pharmacokinetics; rifapentine; tuberculosis.

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Conflict of interest statement

Potential conflicts of interest. A.F.L. has contracts for clinical research unrelated to this work from Gilead, ViiV, and Merck; consulting fees from ViiV. A.A. reports grants from Gilead, ViiV, Roche, GSK and MSD unrelated to this work. S.S. reports grants from ViiV unrelated to the present work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Figure 1.
Figure 1.
Sampling scheme of human immunodeficiency virus RNA evaluations and pharmacokinetic (PK) sampling in A5372. Intensive dolutegravir (DTG) PK sampling occurred on day 0 (DTG dosed once daily) and day 28 (DTG dosed twice daily); sparse sampling occurred on days 3, 14, and 21. Abbreviations: BID, twice daily; D, day; DTG, dolutegravir; HIV, human immunodeficiency virus; INH, isoniazid; QD, once daily; RPT, rifapentine.
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