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.

Conflict of interest statement

Conflicts of Interest: The authors have no financial, consultant, institutional or other relationships that might lead to a bias or conflict of interest. This work was presented in part at the 8th International Workshop on HIV Pediatrics (abstract P_111), in Durban, South Africa, 2016.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Figure 1.. Adjusted z-scores means and 95% confidence intervals for length-for-age (a), weight-for-age (b), weight-for-height (c), and head circumference-for-age (d) of AHEU and HUU children at 12, 24, 36, 48 and 60 months of age study visit, by site

Depicted data points are z scores with 95% confidence intervals (CIs), calculated by use of adjusted longitudinal linear mixed models for continuous outcomes. All models adjusted for measured potential confounders defined a priori and these included maternal age, breastfeeding status at 12 months-of-age, and a summary socioeconomic score. AHEU, antiretroviral and HIV-exposed uninfected; CoM-JHU CRS, College of Medicine-Johns Hopkins University Clinical Research Site; HEU, HIV-exposed uninfected; HUU, HIV-unexposed uninfected; HUU, HIV-unexposed uninfected; MU-JHU CRS, Makerere University-Johns Hopkins University Clinical Research Site.

Figure 2a.

Unadjusted Bar and line graphs of stunting

Figure 2b.

Unadjusted Bar and line graphs of underweight