Purpose: To determine whether isoniazid (INH) reduces the risk of Mycobacterium tuberculosis (MTB) infection in HIV-exposed but uninfected (HEU) children. To determine the epidemiologic and immunologic correlates of MTB infection in HEU.

Study Population: HIV-exposed uninfected (HEU) infants and their mothers

Study Size: 300 infants, 150 per arm 

Treatment Regimen: Isoniazid (INH) ~10 mg/kg (7-15 mg/kg), will be administered once daily to infants in INH arm for 12 months. 

Study Duration: 3 years (12 months of follow-up for each participant)

Primary Objectives:

AIM: 1 Among HEU infants enrolled at approximately 6 weeks of age, compare the risk of acquiring MTB infection during 1 year of follow-up in infants randomized to receive INH vs. no INH using an IGRA assay to determine MTB infection status.

Secondary Objectives:

AIM 2: Determine epidemiologic correlates of MTB infection among infants enrolled in the RCT.

AIM 3: Determine immune correlates of risk of primary MTB infection and their potential interactions with INH. Assays will include infant peripheral blood BCG-specific T-cell responses at approximately 6 weeks post BCG vaccination, and maternal breast milk MTB-specific T-cell responses at approximately 6 weeks postpartum.

Exploratory Objectives:

Investigate the impact of IPT on a combined endpoint of MTB infection, TB disease, and death among HEU infants

Study Sites:                Maternal Child Health (MCH) clinics in Western Kenya (Kisumu, Ahero and Bondo).