Safety Tolerability DDI Short Course Treatment of LTBI Infection With High-dose Rifapentine and Isoniazid or Standard Isoniazid Preventive Therapy in HIV+ Patients (DOLPHIN & DOLPHIN TOO)

Summary

Single-arm, single-center, Phase I/II clinical trial, in four groups. Individuals with HIV infection taking Efavirenz (EFV) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable (Groups 1 and 2) or detectable (Group 3 and 4) HIV viral load and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (Groups 1 and 2) or lamivudine/tenofovir (Groups 3 and 4). Group 1 and 2 will receive weekly HP for 12 total doses starting 8 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least eight weeks (and have not received efavirenz or nevirapine for at least two months) who have an undetectable HIV viral load may also participate. Individuals with HIV infection who are ART treatment naïve at any HIV viral load level and have an indication for TPT will start DTG and be enrolled to receive standard IPT (Group 3) or HP (Group 4) initiated at the same time as DTG. Group 3 and 4 will be enrolled after follow up of Group 1 and 2 has been completed.

Timeline

Start

2018-01-18

Primary completion

2022-12-07

Completion

2022-12-07

Publications

• Weld ED, Beattie T, Moodley J, Mapendere M, Salles I, Solans BP, Nonyane BAS, Wiesner L, Nielson T, Edward VA, Chihota V, Savic RM, Dooley KE, Chaisson RE, Churchyard GJ; DOLPHIN-TOO Study Team; Unitaid IMPAACT4TB Research Group. Simultaneous initiation of dolutegravir-based antiretroviral therapy and once-weekly rifapentine and isoniazid for tuberculosis prevention in antiretroviral-naive people with HIV: an open-label, non-randomised, phase 1/2 trial. Lancet HIV. 2025 Jun;12(6):e428-e439. doi: 10.1016/S2352-3018(25)00002-5. Epub 2025 May 8.
• Jarrett RT, van der Heijden Y, Shotwell MS, Chihota V, Marzinke MA, Chaisson RE, Dooley KE, Churchyard GJ. High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus. Antimicrob Agents Chemother. 2023 Feb 16;67(2):e0129722. doi: 10.1128/aac.01297-22. Epub 2023 Jan 9.
• Dooley KE, Savic R, Gupte A, Marzinke MA, Zhang N, Edward VA, Wolf L, Sebe M, Likoti M, Fyvie MJ, Shibambo I, Beattie T, Chaisson RE, Churchyard GJ; DOLPHIN Study Team. Once-weekly rifapentine and isoniazid for tuberculosis prevention in patients with HIV taking dolutegravir-based antiretroviral therapy: a phase 1/2 trial. Lancet HIV. 2020 Jun;7(6):e401-e409. doi: 10.1016/S2352-3018(20)30032-1. Epub 2020 Mar 30.

Drugs

Indications