Maternal HIV status and risk of infant M. tuberculosis infection


BACKGROUND: The effect of maternal HIV on infant M. tuberculosis(Mtb) infection risk is not well-characterized. Young children with Mtb infection are at high risk of developing active tuberculosis (TB).
METHODS: Pregnant women with and without HIV and their children were enrolled in a longitudinal cohort in western Kenya. Mothers had interferon gamma-release assays (IGRA, QFT-Plus) and tuberculin skin tests (TST) during enrollment in pregnancy; children underwent TST at 12 and 24 months of age (TST+ = '¥5mm for HIV+, '¥10mm for HIV-). We estimated incidence and correlates of 24-month cumulative infant Mtb infection (TST positivity) using Cox proportional hazards regression.
RESULTS: Among 322 infants with TST, 170 (53%) were HIV-exposed and 152 (47%) were HIV-unexposed. Median infant age at enrollment was 6.6 weeks (IQR 6.1-10.0); most received BCG vaccination (320, 99%). Thirty-nine (12%) mothers were TST+ and 102 (32%) were QFT-Plus+. Among 170 HIV-exposed infants, 154 (95%) received ARVs for PMTCT and 141 (83%) of their mothers had ever received isoniazid preventive therapy (IPT).
Twenty-two (6.8%) infants had at least one positive TST for a 24-month cumulative Mtb infection incidence of 3.6/100 PY (95%CI 2.4-5.4/100 PY). Ten percent (17/170) of HIV-exposed and 3.3% (5/152) HIV-unexposed children had at least one positive TST for a 24-month cumulative incidence of 5.3 among HIV-exposed vs. 1.7/100PY for unexposed children (HR 3.1 [95%CI 1.2-8.5], p=0.024). The majority of TST conversions occurred in the first year of life (12 months 5.1 vs. 12-24 months 2.0/100 PY, HR 2.5 [95%CI 0.9-8.8], p=0.06). Infant Mtb infection was associated with maternal TST positivity (HR 2.9 [95%CI 1.1-7.4], p=0.03), but not QFT-Plus positivity (HR 1.2 [95%CI 0.5-2.7], p=0.74). Among HIV-exposed children, Mtb infection incidence was similar regardless of maternal IPT (IPT 4.5 vs. no IPT 6.3/100PY, HR 0.7 [95%CI 0.2-2.1], p=0.48).
CONCLUSIONS: Infant Mtb infection incidence (as measured by TST) by 24 months of age was ~3.1-fold higher among HIV-exposed children, despite high levels of maternal IPT. Overall, there was a trend for higher incident TST conversions in the first compared to the second year of life, which was similar among both HIV-exposed and unexposed infants.

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