A5406 hypothesizes that dolutegravir (DTG) 50 mg taken twice daily will provide adequate exposures to maintain viral suppression when dosed with rifapentine (RPT) 1200 mg for HIV-associated TB.
This is an open-label, single arm, phase II, multicenter PK study to investigate the effect of daily RPT 1200 mg on DTG exposure in participants with HIV-associated TB. Adults with HIV with newly diagnosed DS-TB who are not currently on ART will be recruited around the time of DS TB diagnosis. At study entry, the 2HPZM/2HPM regimen will be initiated for anti-tuberculosis (anti-TB) therapy and continued for 17 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Dolutegravir (DTG) 50 mg orally BID (\~12 hours apart) plus TDF/3TC, from study week 6 until 2 weeks after completion of TB treatment: Morning dose DTG 50 mg QD plus TDF/3TC from study-supplied ARV regimen. Evening dose: DTG 50 mg orally QD from study-supplied source.
DTG 50 mg orally QD plus TDF/3TC from two weeks after completion of TB treatment to end of study (week 48).
Daily rifapentine-moxifloxacin plus isoniazid and pyrazinamide regimen
University of Cape Town Lung Institute (UCTLI) CRS (Site # 31792)
Mowbray, Cape Town, Western Cape, South Africa
Durban International CRS (Site # 11201)
Westridge, Durban RSA, South Africa
South African Tuberculosis Vaccine Initiative (SATVI) CRS (Site # 31793)
Worcester, Western Province, South Africa
Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (Site # 31802)
Bangkok, Thailand
Model-simulated 5th percentile and corresponding 95% confidence interval of DTG minimum concentrations (Cmin) at 50 mg BID when co-administered with daily RPT 1200 mg plus HZM
Time frame: 48 Weeks
DTG minimum concentration (Cmin)
Model-derived participant- and week-specific estimate of DTG Cmin
Time frame: 48 Weeks
DTG minimum concentration (Cmax)
Model-derived participant- and week-specific estimate of DTG Cmax
Time frame: 48 Weeks
DTG area under the concentration-time curve (AUC0-24)
Model-derived participant- and week-specific estimate of DTG AUC0-24
Time frame: 48 Weeks
Number of participants who experience Grade 3 or higher AEs
Time frame: Weeks 6-17
Number of participants who have a diagnosis of rifamycin hypersensitivity
Time frame: Weeks 6-17
Number of participants who experience ALT ≥3xULN with symptoms/jaundice or ALT ≥5xULN
Time frame: Weeks 6-17
Number of participants who prematurely discontinue study drugs DTG and/or RPT
Time frame: Weeks 6-17
Proportion of participants with HIV-1 viral load below 50 copies/mL
Time frame: Weeks 10, 14, 21, and 30
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Daily rifapentine-moxifloxacin plus isoniazid regimen