Isoniazid preventive therapy during infancy does not adversely effect growth among HIV-exposed uninfected children: secondary analysis of data from a randomized controlled trial

BackgroundIsoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure. MethodsThe infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight [≥]2.5 kg, and gestation [≥]37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms. ResultsAmong 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ ({beta}=0.04 [95% CI:-0.14, 0.22]), HAZ ({beta}=0.14 [95% CI:-0.06, 0.34]), and WHZ [{beta}=-0.07 [95% CI:-0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase ({beta} to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm. ConclusionIPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.