Decreased growth among antiretroviral drug and HIV-exposed uninfected versus unexposed children in Malawi and Uganda

Abstract

Objective: To compare growth among antiretroviral drug and maternal HIV-exposed uninfected (AHEU) versus age-matched and sex-matched HIV-unexposed uninfected (HUU) children.

Design: Prospective cohort of AHEU children identified from the PROMISE trial (NCT01061151: clinicaltrials.gov registry) and age-matched and sex-matched HUU controls from child-wellness clinics, enrolled (September 2013 to October 2014) in Malawi and Uganda.

Methods: Weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head-circumference-for-age (HCAZ) z-scores were derived at 12 months and 24 months of age. Wilcoxon Rank-Sum and Fisher's exact tests were used for unadjusted exposure group comparisons. Generalized Estimating Equations models estimated adjusted relative risks (aRR) for poor growth outcomes.

Results: Overall, 471 (50.5%) AHEU and 462 (49.5%) HUU children were assessed. Ugandan AHEU compared with HUU children had significantly lower mean LAZ (P < 0.001) and WAZ (P < 0.001) at 12 and 24 months of age and HCAZ (P = 0.016) at 24 months, with similar but not significant differences among Malawian AHEU and HUU children. The risk of stunting (more than two standard deviations below the WHO population LAZ median) was increased among AHEU versus HUU children: aRR = 2.13 (95% confidence interval (CI): 1.36-3.33), P = 0.001 at 12 months, and aRR = 1.67 (95% CI 1.16-2.41), P = 0.006 at 24 months of age in Uganda; and aRR = 1.32 (95% CI 1.10-1.66), P = 0.018, at 24 months of age in Malawi. The risk of HCAZ below WHO median was increased among AHEU versus HUU children at 24 months of age, aRR = 1.35 (95% CI 1.02-1.79), P = 0.038 in Uganda; and aRR = 1.35 (95% CI 0.91-2.02), P = 0.139 in Malawi.

Conclusion: Perinatal exposures to maternal HIV and antiretroviral drugs were associated with lower LAZ (including stunting), WAZ and HCAZ at 24 months of age compared with HUU children.

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.

Figures

Figure 1.

Study flow diagram. Enrolment and study evaluations at the study clinics in Malawi and Uganda, August 2013 – April 2016 Legend: AHEU, Antiretroviral and HIV exposed uninfected children; HUU, HIV Unexposed Uninfected children; CoM-JHU CRS (College of Medicine-Johns Hopkins University Clinical Research Site); MU-JHU CRS (Makerere University – Johns Hopkins University Clinical Research Site).

Figure 2.

Adjusted means of Z-scores and 95% CIs for weight-for-age (A), length-for-age (B), weight-for-height (C), and head circumference-for-age (D) of AHEU and HUU children at 12 and 24 months by site Legend: Depicted data points are Z scores with 95% confidence intervals (CIs), calculated by use of adjusted Generalized Estimation Equations (GEE) linear regression models. All models adjusted for measured potential confounders defined aprior and these included breastfeeding statuses; maternal-age; electricity/gas use and tap-water use. HEU=HIV-exposed uninfected. HUU=HIV-unexposed uninfected. AHEU, Antiretroviral and HIV exposed uninfected children; HUU, HIV Unexposed Uninfected children; CoM-JHU CRS (College of Medicine-Johns Hopkins University Clinical Research Site); MU-JHU CRS (Makerere University – Johns Hopkins University Clinical Research Site).