A5406: Pharmacokinetics and Safety of Double-dose Dolutegravir When Used with Rifapentine for HIV-associated Tuberculosis

A5406 is a study for people with pulmonary drug-sensitive (DS) tuberculosis (TB) without evidence of resistance to the TB drugs isoniazid (INH) or rifampin (RIF) and with HIV. All participants will receive anti-TB treatment (2HPZM: 8 weeks of rifapentine [RPT]-moxifloxacin [MOX] plus INH and pyrazinamide, then 2HPM: 9 weeks of RPT-MOX plus INH). Dolutegravir (DTG)-based anti-HIV therapy (ART) will be taken from week 6 until the end of the study (week 48), with a double-dose of DTG for the first 12 weeks.

• The purpose of this study is to determine if taking a medicine called RPT to treat drug‑sensitive TB affects the levels of DTG in the blood or not.

• Have pulmonary TB with or without history of prior treatment, and without known resistance of INH or RIF.
• Cannot have more than 5 days of treatment for the current TB episode.
• Have HIV and planning to take DTG-based ART.
• ART-naïve or currently not on ART for 12 consecutive weeks prior to TB diagnosis.
• 18 years of age or older.

For this one group study, all participants will receive the following anti-TB therapy:

• 2HPZM (RPT, MOX, INH, and pyrazinamide) daily from day 0 to week 8.
• 2HPM (RPT, MOX, INH) daily from week 9 to week 17.

After 6 weeks of TB therapy, participants will start taking DTG-based ART twice daily. The double‑dose DTG will be continued for 2 weeks after completion of TB therapy, after which DTG will be reduced to standard dose once daily.

Participants will also take pyridoxine (vitamin B6) with each dose of INH.

The anti-TB therapy (2HPZM/2HPM) and ART (DTG plus TDF/3TC [tenofovir disoproxil fumarate/lamivudine]) will be provided by the study, including the extra dose of DTG. Pyridoxine will not be provided by the study.

Participants will be in this study for about 48 weeks. This includes 17 weeks of anti-TB study treatment, and ART from week 6 to week 48.