The investigators want to know if ultra-short, effective treatment for latent tuberculosis (TB) infection (LTBI) could dramatically reduce the global incidence of active TB or not. The investigators hypothesize that short-course (4-week) daily isoniazid/rifapentine (INH/RPT) (1HP) is not inferior to standard -course (12 weeks) INH/RPT weekly regimen (3HP) for the prevention of TB in human immunodeficiency virus (HIV)-infected individuals.
This study is a multicenter, randomized, open-label, phase III clinical trial comparing a 4-week daily INH/RPT regimen (1HP) to a 12-weekly INH/RPT (3HP) for the treatment of LTBI in HIV-infected participants without evidence of active TB. The primary objective will be efficacy of active TB prevention. The study will also assess safety and tolerability of the regimens, adherence to the treatments, and patterns of antibiotic resistance among Mycobacterium tuberculosis (MTB) isolates in participants who fail on these prophylactic regimens. Under this study, there is one substudy entitled, "Pharmacokinetic study of rifapentine, dolutegravir, and tenofovir alafenamide in HIV-infected individual with latent tubersulosis infection". There will be a subgroup of patients who will participate in this pharmacokinetic study of rifapentine and dolutegravir (DTG) / tenofovir alafenamide (TAF). Randomization is based on cluster of differentiation 4 (CD4) categories : \< 200, 200-350, \> 500 cells/mm3 and VL \<50 or \>50 copies/ml.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
2,500
Isoniazid/Rifapentine daily (4 weeks) plus pyridoxine (vitamin B6)
Isoniazid/Rifapentine 12-weekly plus pyridoxine (vitamin B6)
Klang Hospital
Bangkok, Thailand
Bhumibol Adulyadej Hospital
Bangkok, Thailand
HIV-NAT, Thai Red Cross AIDS Research Centre
Bangkok, Thailand
King Chulalongkorn Memorial Hospital
Bangkok, Thailand
Police General Hospital
Bangkok, Thailand
Taksin Hospital
Bangkok, Thailand
the Public Health Centre 28 Krung thon buri
Bangkok, Thailand
Sanpatong Hospital
Chiang Mai, Thailand
Chiangrai Prachanukroh Hospital
Chiang Rai, Thailand
Queen Savang Vadhana Memorial Hospital
Chon Buri, Thailand
...and 6 more locations
efficacy in preventing active TB (proportion of participants that do not have active TB by the end of the study)
proportion of participants that do not have active TB by the end of the study
Time frame: 3 years
safety of the regimens (proportion of participants that do not have any side effects throughout the study period)
proportion of participants that do not have any side effects throughout the study period
Time frame: 3 years
tolerability to the regimens (proportion of participants that can complete the treatment course)
proportion of participants that can complete the treatment course
Time frame: 3 years
prevalence of drug resistance of MTB
proportion of participants with drug resistance to MTB
Time frame: 3 years
severity of the condition
proportion of participants that have side effects of grade more than or equal to 3 signs
Time frame: 3 years
presence of symptoms
proportion of participants that have symptoms during the study period
Time frame: 3 years
level of CBC
assess the level of CBC
Time frame: 3 years
level of ALT
assess the level of ALT
Time frame: 3 years
level of AST
assess the level of AST
Time frame: 3 years
level of total bilirubin
assess the level of total bilirubin
Time frame: 3 years
level of ALK
assess the level of ALK
Time frame: 3 years
level of creatinine
assess the level of creatinine
Time frame: 3 years
death
time from randomization to death from any cause (TB and non TB events)
Time frame: 3 years
when TB culture becomes positive
how much time does it take to have positive TB culture
Time frame: 3 years
when TB is confirmed by clinical examination
how much time does it take to have TB diagnosed via clinical examination
Time frame: 3 years
adherence to LTBI treatment
proportion of pills missed during treatment period based on self report
Time frame: 3 years
consistency of taking LTBI treatment
proportion of pills missed during treatment period based on clinical assessment
Time frame: 3 years
treatment discontinuation
proportion of participants with permanent LTBI treatment discontinuation due to all causes
Time frame: 3 years
discontinuation of study due to adverse drug reactions
Proportion of participants that have discontinued the study because of adverse drug reactions
Time frame: 3 years
CD4 count
CD4 count at baseline
Time frame: 3 years
CD4 count to confirmed or probable TB
CD4 count at time from randomization to culture-confirmed or probable TB
Time frame: 3 years
time it takes for TB to be confirmed by IGRA
how much time does it take to confirm TB diagnosis via IGRA
Time frame: 3 years
TST result at baseline
TST result at day 0
Time frame: day 0
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