Maternal breastfeeding and education impact infant growth and development more than in-utero HIV/antiretroviral therapy exposure in context of universal antiretroviral therapy.

BACKGROUND: Exposure to HIV and antiretroviral therapy (ART) in utero may influence infant growth and development. Most available evidence predates adoption of universal ART (Option B+ ART regimens). In a recent cohort, we compared growth and development in HIV-exposed uninfected (HEU) to HIV-unexposed (HUU) infants. DESIGN: Prospective cohort study: data from Impact of Maternal HIV on Mycobacterium Tuberculosis Infection among Peripartum Women and their Infants (MiTIPS) in Western Kenya. METHODS: Women were enrolled during pregnancy. Mother-infant pairs were followed until 24 months postpartum. We used multivariable linear mixed-effects models to compare growth rates [weight-for-age z score (WAZ) and height-for-age z score (HAZ)] and multivariable linear regression to compare overall development between HEU and HUU children. RESULTS: About 51.8% (184/355) of the infants were HEU, 3.9% low birthweight (<2.5 kg), and 8.5% preterm (<37 gestational weeks). During pregnancy, all mothers of HEU received ART; 67.9% started ART prepregnancy, and 87.3% received 3TC/FTC, TDF, and EFV. In longitudinal analyses, HEU children did not differ significantly from HUU in growth or development ( P  > 0.05 for all). In the combined HEU/HUU cohort, higher maternal education was associated with significantly better growth and development: WAZ [ ß â€Š= 0.18 (95% CI 0.01-0.34)], HAZ [ ß â€Š= 0.26 (95% CI 0.04-0.48)], and development [ ß â€Š= 0.24 (95% CI 0.02-0.46)]. Breastfeeding was associated with significantly better HAZ [ ß =0.42 (95% CI 0.19-0.66)] and development [ ß â€Š=0.31 (95% CI 0.08-0.53)]. CONCLUSION: HEU children in the setting of universal maternal ART had a similar growth trajectory and development to HUU children. Breastfeeding and maternal education improved children's weight, height, and overall development irrespective of maternal HIV status.

Effect of tuberculosis-HIV co-treatment on clinical and growth outcomes among hospitalized children newly initiating antiretroviral therapy.

OBJECTIVE: Evaluate effects of tuberculosis (TB)-HIV co-treatment on clinical and growth outcomes in children with HIV (CHIV). DESIGN: Longitudinal study among Kenyan hospitalized ART-naive CHIV in the PUSH trial (NCT02063880). METHODS: CHIV started ART within 2 weeks of enrollment; Anti-TB therapy was initiated based on clinical and TB diagnostics. Children were followed for 6 months with serial viral load, CD4%, and growth assessments [weight-for-age z -score (WAZ), height-for-age z -score (HAZ), and weight-for-height z -score (WHZ)]. TB-ART treated and ART-only groups were compared at 6 months post-ART for undetectable viral load (<40 c/ml), CD4% change, and growth using generalized linear models, linear regression, and linear mixed-effects models, respectively. RESULT: Among 152 CHIV, 40.8% (62) were TB-ART treated. Pre-ART, median age was 2.0 years and growth was significantly lower, and viral load significantly higher in the TB-ART versus ART-only group. After 6 months on ART, 37.2% of CHIV had undetectable viral load and median CD4% increased by 7.2% (IQR 2.0-11.6%) with no difference between groups. The TB-ART group had lower WAZ and HAZ over 6 month follow-up [WAZ -0.81 (95% CI: -1.23 to -0.38], P  < 0.001; HAZ -0.15 (95% CI: -0.29 to -0.01), P  = 0.030] and greater rate of WAZ increase in analyses unadjusted and adjusted for baseline WAZ [unadjusted 0.62 (95% CI: 0.18-1.07, P  = 0.006) or adjusted 0.58 (95% CI: 0.12-1.03, P  = 0.013)]. CONCLUSION: TB-HIV co-treatment did not adversely affect early viral suppression and CD4 + recovery post-ART. TB-ART-treated CHIV had more rapid growth reconstitution, but growth deficits persisted, suggesting need for continued growth monitoring.

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

Background: Isoniazid 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. Methods: The 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. Results: Among 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 (ß=0.04 [95% CI:-0.14, 0.22]), HAZ (ß=0.14 [95% CI:-0.06, 0.34]), and WHZ [ß=-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 (ß to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm. Conclusion: IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.

Effect of pregnancy versus postpartum maternal isoniazid preventive therapy on infant growth in HIV-exposed uninfected infants: a post-hoc analysis of the TB APPRISE trial.

Background: Isoniazid preventive therapy (IPT) initiation during pregnancy was associated with increased incidence of adverse pregnancy outcomes in the TB APPRISE trial. Effects of in utero IPT exposure on infant growth are unknown. Methods: This post-hoc analysis used data from the TB APPRISE trial, a multicentre, double-blind, placebo-controlled trial, which randomised women to 28-week IPT starting in pregnancy (pregnancy-IPT) or postpartum week 12 (postpartum-IPT) in eight countries with high tuberculosis prevalence. Participants were enrolled between August 2014 and April 2016. Based on modified intent-to-treat analyses, we analysed only live-born babies who had at least one follow-up after birth and compared time to infant growth faltering between arms to 12 weeks and 48 weeks postpartum in overall and sex-stratified multivariable Cox proportional hazards regression. Factors adjusted in the final models include sex of infant, mother's baseline BMI, age in years, ART regimen, viral load, CD4 count, education, and household food insecurity. Results: Among 898 HIV-exposed uninfected (HEU) infants, 447 (49.8%) were females. Infants in pregnancy-IPT had a 1.47-fold higher risk of becoming underweight by 12 weeks (aHR 1.47 [95% CI: 1.06, 2.03]) than infants in the postpartum-IPT; increased risk persisted to 48 weeks postpartum (aHR 1.34 [95% CI: 1.01, 1.78]). Maternal IPT timing was not associated with stunting or wasting. In sex-stratified analyses, male infants in the pregnancy-IPT arm experienced an increased risk of low birth weight (LBW) (aRR 2.04 [95% CI: 1.16, 3.68), preterm birth (aRR 1.81 [95% CI: 1.04, 3.21]) and becoming underweight by 12 weeks (aHR 2.02 [95% CI: 1.29, 3.18]) and 48 weeks (aHR 1.82 [95% CI: 1.23, 2.69]). Maternal IPT timing did not influence growth in female infants. Interpretation: Maternal IPT during pregnancy was associated with an increased risk of LBW, preterm birth, and becoming underweight among HEU infants, particularly male infants. These data add to prior TB APPRISE data, suggesting that IPT during pregnancy impacts infant growth, which could inform management, and warrants further examination of mechanisms. Funding: The TB APPRISE study Supported by the National Institutes of Health (NIH) (award numbers, UM1AI068632 [IMPAACT LOC], UM1AI068616 [IMPAACT SDMC], and UM1AI106716 [IMPAACT LC]) through the National Institute of Allergy and Infectious Diseases, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number, HHSN275201800001I) and the National Institute of Mental Health.