Growth deficits in antiretroviral and HIV-exposed uninfected versus unexposed children in Malawi and Uganda persist through 60 months of age

Abstract

Objective:To compare childhood physical growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) compared with HIV-unexposed uninfected (HUU) children.Design:Longitudinal follow-up of PROMISE trial (NCT01061151) AHEU and age-matched and sex-matched HUU children, enrolled (September 2013 to October 2014) in Malawi and Uganda.Method:We compared WHO population standardized z-scores [height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ), head-circumference-for-age (HCAZ) at 12, 24, 36, 48, and 60 months of age]. We evaluated HUU versus AHEU [in-utero combination antiretroviral treatment (cART) versus Zidovudine (ZDV) alone]; stratified by country, using longitudinal linear and generalized linear mixed models.Results:Of 466 Malawian and 477 Ugandan children, median maternal age at enrollment was 24.5 years (Malawi) and 27.8 years (Uganda); more than 90% were breastfed through 12 months except Uganda AHEU (64.0%). HAZ scores (adjusted for maternal age, breastfed, and socioeconomic status) were lower among AHEU versus HUU children at every time point, significant (P < 0.05) among Ugandan but not Malawian children. Similar patterns were seen for WAZ but not for WHZ or HCAZ scores. High stunting was observed in both countries, significantly higher in Malawi; and higher among AHEU versus HUU children through 48 months of age, significantly (P < 0.05) among Ugandan but not Malawian children. We found no differences in childhood growth trajectories with in-utero exposures to ZDV compared with cART.Conclusion:AHEU versus HUU children had lower median LAZ and WAZ scores persisting through 60 months of age. However, proportions of children with stunting or underweight decreased after 24 months of age.

Risk factors for stunting in children who are HIV‐exposed and uninfected after Option B+ implementation in Malawi

“…Stunting typically begins in early infancy and continues throughout the first 2 years of life (Hoddinott et al, 2013 ; Victora et al, 2010 ). Our data highlight that linear growth faltering occurred early, with rates increasing between age 12 and 24 months, similar to findings from other Eastern and Southern African studies (Aizire et al, 2020 ; Evans et al, 2021 ; Fowler et al, 2021 ; Jumare et al, 2019 ; S. M. Le Roux et al, 2019 ; Ndiaye et al, 2021 ; Sudfeld et al, 2016 ). These rates are congruous with that reported in 2015–2016 in the general Malawian population, where stunting peaked at 42%–45% between the ages of 18 and 47 months (The DHS Programme, 2017 ).…”

“…In a longitudinal analysis of ART-exposed Malawian CHEU, median LAZ and WAZ were lower through 60 months of age compared to children HIV-unexposed (Fowler et al, 2021).…”

“…While this has improved maternal health and survival, partially mitigating disparities in morbidity and mortality between CHEU and children HIV-unexposed (Brennan et al, 2016;S. M. Le Roux et al, 2016), available evidence suggests poor growth persists as a problem for CHEU (Aizire et al, 2020;Evans et al, 2021;Fowler et al, 2021;Jumare et al, 2019;S. M. Le Roux et al, 2019;Ndiaye et al, 2021;Sudfeld et al, 2016).…”

“…In South Africa, two large cohort studies demonstrated breastfed ART‐exposed CHEU present with lower length‐for‐age (LAZ) z‐scores and greater prevalence of stunting than children HIV‐unexposed (Evans et al, 2021 ; S. M. Le Roux et al, 2019 ), with similar findings for weight‐for‐age (WAZ) z‐scores and underweight (Evans et al, 2021 ). In a longitudinal analysis of ART‐exposed Malawian CHEU, median LAZ and WAZ were lower through 60 months of age compared to children HIV‐unexposed (Fowler et al, 2021 ).…”

“…With widespread availability of antiretroviral therapy (ART) for prevention of vertical transmission (PVT) and treat‐all policies (i.e., universal treatment of HIV), ART use among pregnant WLHIV has increased substantially. While this has improved maternal health and survival, partially mitigating disparities in morbidity and mortality between CHEU and children HIV‐unexposed (Brennan et al, 2016 ; S. M. Le Roux et al, 2016 ), available evidence suggests poor growth persists as a problem for CHEU (Aizire et al, 2020 ; Evans et al, 2021 ; Fowler et al, 2021 ; Jumare et al, 2019 ; S. M. Le Roux et al, 2019 ; Ndiaye et al, 2021 ; Sudfeld et al, 2016 ). Although ART use during pregnancy is generally safe, specific antiretrovirals have been associated with intrauterine growth restriction and preterm birth (Uthman et al, 2017 ).…”