Twice-Daily Dolutegravir Based Antiretroviral Therapy with One Month of Daily Rifapentine and Isoniazid (1HP) for TB Prevention.

BACKGROUND: One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashort option for TB prevention in people with HIV (PWH). However, rifapentine may decrease antiretroviral drug concentrations and increase the risk of virologic failure. ACTG A5372 evaluated the effect of 1HP on the pharmacokinetics of twice daily dolutegravir.

METHODS: A5372 was a multicenter, pharmacokinetic study in PWH (≥18 years) already on dolutegravir-containing antiretroviral therapy with HIV RNA < 50 copies/mL. Participants received daily rifapentine/isoniazid (600mg/300mg) for 28 days as part of 1HP. Dolutegravir was increased to 50mg 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. Thirty-one of 32 had HIV RNA levels <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 vs. 1987ng/mL (1331, 2278) on day 28 (day 28:day 0 GMR 1.05, [90% CI 0.93-1.2]; p = 0.43). No serious adverse events were reported.

CONCLUSION: Dolutegravir trough concentrations with 50mg 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 TB prevention.