Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)
Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)
HIV-infected people have an increased risk of developing active tuberculosis (TB). At the
 time the study was designed, the standard course of treatment for TB was 6 to 9 months of
 isoniazid (INH).This study compared the safety and effectiveness of a 4-week regimen of
 rifapentine (RPT) plus INH versus a standard 9-month regimen of INH in HIV-infected people
 who are at risk of developing active TB.
The World Health Organization (WHO) estimated that in 2017 there were 10 million new cases of
 TB, and 1.6 million people died as a result of TB. Among new TB cases, it is estimated that
 920,000 occurred in people who were HIV-coinfected, and 23% of TB deaths were among
 HIV-coinfected individuals. In Africa, TB is the leading AIDS-related opportunistic
 infection. Latent TB infection occurs when people are infected with the bacteria that cause
 TB, but they do not have any symptoms of TB infection. Latent TB can develop into active TB,
 and HIV-infected people have an increased risk of progressing from latent TB to active TB.
 INH is a medication that is prescribed for people with latent TB to help prevent active TB
 from developing. The standard INH treatment regimen is 6 to 9 months; a shorter treatment
 regimen of 3 months of once-weekly RPT plus INH has proven to be as effective and improved
 adherence. The purpose of this study was to compare the safety and effectiveness of a 4-week
 daily regimen of RPT plus INH to a standard 9-month daily INH regimen for TB prevention in
 HIV-infected individuals.

 This study enrolled HIV-infected people who did not have evidence of active TB but who were
 at high risk of developing active TB. Participants were randomly assigned to receive RPT and
 INH once a day for 4 weeks or INH once a day for 9 months. All participants received
 pyridoxine (vitamin B6) with each dose of INH to help prevent possible side effects. Study
 visits occurred at baseline and Weeks 2, 4, 8, 12, 16, 20, 24, and 36. At select study
 visits, participants had a physical exam, clinical assessment, blood collection, and a chest
 radiograph or chest computed tomography (CT) scan (if needed). Some participants had their
 blood stored for future testing. Follow-up study visits occurred every 12 weeks starting at
 Week 48 and continued for 3 years after the last participant enrolled.
Inclusion Criteria:

 -  HIV-1 infection

 -  Tuberculin skin test (TST) reactivity greater than or equal to 5 mm or a positive
 interferon gamma release assay (IGRA) at any time prior to study entry, OR living in a
 high TB burden area. More information on this criterion can be found in the protocol.

 -  Laboratory values obtained within 30 days prior to study entry:

 1. Absolute neutrophil count (ANC) greater than 750 cells/mm^3

 2. Hemoglobin greater than or equal to 7.4 g/dL

 3. Platelet count greater than or equal to 50,000/mm^3

 4. AST (SGOT) and ALT (SGPT) less than or equal to three times the upper limit of
 normal (ULN)

 5. Total bilirubin less than or equal to 2.5 times the ULN

 -  Chest radiograph or chest CT scan without evidence of active tuberculosis, unless one
 has been performed within 30 days prior to entry

 -  Female participants of reproductive potential must have a negative serum or urine
 pregnancy test performed within 7 days prior to study entry. More information on this
 criterion can be found in the protocol.

 -  All participants must agree not to participate in a conception process (e.g., active
 attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization)
 while receiving RPT and for 6 weeks after stopping this drug

 -  Female participants who are participating in sexual activity that could lead to
 pregnancy must agree to use one reliable non-hormonal form of contraceptive while
 receiving RPT and for 6 weeks after stopping this drug. More information on this
 criterion can be found in the protocol.

 -  Weight of greater than or equal to 30 kg

 -  Participant or legal guardian is able and willing to provide informed consent

 Exclusion Criteria:

 -  Treatment for active or latent TB (pulmonary or extrapulmonary) within 2 years prior
 to study entry or, at screening, presence of any confirmed or probable TB based on
 criteria listed in the current ACTG Diagnosis Appendix

 -  History of multi-drug resistant (MDR) or extensively-drug resistant (XDR) TB at any
 time prior to study entry

 -  Known exposure to MDR or XDR TB (e.g., household member of a person with MDR or XDR
 TB) at any time prior to study entry

 -  Treatment for more than 14 consecutive days with a rifamycin or more than 30
 consecutive days with INH at any time during the 2 years prior to enrollment

 -  For participants taking antiretroviral therapy (ART) at study entry, only approved
 nucleoside reverse transcriptase inhibitors (NRTIs) with efavirenz (EFV) or nevirapine
 (NVP) for at least 4 weeks were permitted

 -  History of liver cirrhosis at any time prior to study entry.

 -  Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/or
 light stools within 90 days prior to study entry

 -  Diagnosis of porphyria at any time prior to study entry

 -  Peripheral neuropathy greater than or equal to Grade 2 according to the December 2004
 (Clarification, August 2009) Division of AIDS (DAIDS) Toxicity Table, within 90 days
 prior to study entry

 -  Known allergy/sensitivity or any hypersensitivity to components of study drugs or
 their formulation

 -  Active drug or alcohol use or dependence that, in the opinion of the site
 investigator, would interfere with adherence to study requirements

 -  Serious illness requiring systemic treatment and/or hospitalization within 30 days
 prior to study entry

 -  Breastfeeding