Preventing Mycobacterium tuberculosis infection in HIV-exposed infants
Grace John-Stewart, M.D., Ph.D.
BACKGROUND: No intervention with proven efficacy to prevent MTB infection in HIV-exposed uninfected (HEU) infants is currently available; it is important to develop such an intervention due to high rates of MTB infection and TB disease in this population. Both isoniazid preventive treatment (IPT) and BCG vaccine are used to prevent active TB disease and these interventions may also play a role in preventing MTB infection. Immune mechanisms for their preventive effect are unknown and can be efficiently examined among HEU infants in order to inform new strategies for chemoprophylaxis or TB vaccines for prevention of MTB infection.
GAP: This study will determine whether IPT, BCG-specific immune responses, or maternal breast milk immune responses are associated with protection from MTB infection in HEU children.
1. HEU children who receive IPT will have a decreased risk of MTB infection compared to those who receive no IPT.
2. Lower maternal CD4 count, shorter breastfeeding duration, slower infant growth, and positive paternal HIV status will be associated with infant MTB infection.
3. Infant BCG-specific and maternal breast milk MTB-specific T-cell responses will be associated with decreased infant MTB infection.
METHODS: This randomized trial will involve HIV-exposed uninfected infants born to HIV-infected mothers. Infants will be enrolled at 6 weeks of age and randomized to IPT vs. no IPT and followed for 1 year. MTB infection rates will be compared between RCT arms and cofactors for infant MTB infection will be determined.
IMPACT: Infant IPT could be an important component of TB prophylaxis strategies for HEU and immune mechanisms of protection that are identified by the project could be used for developing new TB drugs and vaccines.