Maternal HIV status and risk of infant M. tuberculosis infection

Title

Maternal HIV status and risk of infant M. tuberculosis infection

Presenter

Jerphason Mecha

Authors

J. Mecha * (1), J.N. Escudero (2), B.A. Richardson (2), E.M. Obimbo (3), D. Matemo (1), J. Kinuthia (1,2,3), G.J. Stewart (2), S.M. LaCourse (2)

Institutions

(1) Kenyatta National Hospital, Nairobi, Kenya, (2) University of Washington, Seattle, WA, United States, (3) University of Nairobi, Nairobi, Kenya

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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