Tuberculosis Preventive Therapy Among Latent Tuberculosis Infection in HIV-infected Individuals

Inclusion Criteria:

1. Documented HIV-1 infection by standard HIV test or plasma HIV-1 RNA viral load andreceived ART within 12 months. Participants received ART more than 12 months wouldbe allowed if CD4 cell counts is less than 350 cells/mm3

2. 18 years and older

3. Evidence of latent TB infection, either by TST ≥5 mm or positive interferon gammarelease assay (IGRA) or history of close contact with active pulmonary TB* within 3months prior entry visit or residing in a high TB burden area** NOTE * close contactis referred to person living/sharing in the same room with active pulmonary TBparticipants for > 4 hours/day

** high TB burden areas are defined as areas with an estimated or reported TBprevalence of 100 to 300/100,000, according to the WHO. Thailand is included in highTB burden areas.

4. Laboratory values obtained within 30 days prior to entry

• Absolute neutrophil count (ANC) >750 cells/mm3

• Hemoglobin >7.4 g/dL

• Platelet count >50,000/mm3

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) <3x upper limit of normal (ULN)

• Total bilirubin <2.5 X ULN

5. Chest radiograph or chest computed tomography (CT) scan without evidence of activetuberculosis, unless one has been performed within 90 days prior to entry.

6. Female participants who are participating in sexual activity that could lead topregnancy must agree to use one reliable non-hormonal form of contraceptive (i.e.,condoms, IUD, diaphragm) during RPT treatment and contraception should be remain to 6 weeks post RPT NOTE Female participants who are not of reproductive potential orwhose male partner(s) have undergone successful vasectomy with documentedazoospermia or have documented azoospermia are eligible without requiring the use ofcontraceptives. Participant-reported history is acceptable documentation ofmenopause, hysterectomy, or bilateral oophorectomy or bilateral tubal ligation.

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

8. Body weight > 40 kg

9. Ability and willingness of participant to provide informed consent

Exclusion Criteria:

1. Treatment for active or latent TB (pulmonary or extrapulmonary) within 2 years priorto study entry or presence of any confirmed or probable active TB at screening.

2. History of Isoniazid (INH) or Rifampicin (RIF)/Rifabutin (RFB) resistant TB at anytime prior to study entry or known exposure to INH or RIF/RFB resistant TB (e.g.,household member of a person with MDR or XDR TB) at any time prior to study entry.

3. Treatment for >14 consecutive days with a rifamycin or >30 consecutive days with INHat any time during the 2 years prior to enrollment.

4. Current or planned use of protease inhibitor-based ART.

5. Currently on a salvage ART regimen, defined as a regimen started due to confirmedHIV virologic failure on a prior ART regimen or due to known HIV drug resistance.

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

7. Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/orlight stools within 90 days prior to entry.

8. Diagnosis of porphyria at any time prior to study entry.

9. Peripheral neuropathy ≥Grade 2 according to the Division of AIDS (DAIDS) ToxicityTable, within 90 days prior to study entry.

10. Known allergy/sensitivity or any hypersensitivity to components of study drug(s) ortheir formulation.

11. Active drug or alcohol use or dependence that, in the opinion of the siteinvestigator, would interfere with adherence to study requirements.

12. Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to entry.

13. Pregnancy or breastfeeding