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.

Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia

“…In these high prevalence settings, more than 95% of pregnant WLHIV receive ART in pregnancy, resulting in the majority of infants who are HEU having dual exposure to HIV and ARVs. While not all studies show the same early adverse outcomes of in-utero exposures, some have found alterations in growth [ 8 , 9 , 16 – 20 ]. In particular, infants who are HEU may experience a higher risk of suboptimal growth in infancy [ 4 , 5 , 8 , 13 , 16 – 18 , 20 – 22 ] with these effects persisting through to school-going age [ 7 , 23 ].…”

“…While not all studies show the same early adverse outcomes of in-utero exposures, some have found alterations in growth [ 8 , 9 , 16 – 20 ]. In particular, infants who are HEU may experience a higher risk of suboptimal growth in infancy [ 4 , 5 , 8 , 13 , 16 – 18 , 20 – 22 ] with these effects persisting through to school-going age [ 7 , 23 ]. Many studies however, (1) lack comparison with children who are HU.…”

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“…These findings are an important addition to the literature in that our analysis from a multi-site randomized clinical trial in resource limited multinational settings examines the effect on growth attributable to maternal ART alone versus extended NVP prophylaxis without added exposure to advanced maternal HIV disease or truncated breastfeeding-a notable gap not addressed in publications before antiretroviral treatment became available [1] and pre-dating the era of universal ART [22,23] when ART was reserved for women with advanced HIV disease. These data are aligned with current literature in the era of universal ART and extended breastfeeding which document suboptimal postnatal growth despite high HIV-free survival when compared to WHO population norms [2] and to HIV unexposed infants [2,5,24].…”

“…Prior research suggests that HIV-exposed uninfected infants (HEUs) have diminished somatic growth compared to unexposed infants [1][2][3][4][5]. Wasting, stunting and underweight more than double the hazard of childhood mortality [6][7][8] while their early life effect on neurocognition diminishes developmental potential in adult life [9].…”

Association of serum PUFA and linear growth over 12 months among 6–10 years old Ugandan children with or without HIV

“…Access to antiretroviral therapy (ART) contributes to improved growth among CPHIV (5) , but immune restoration is seldom complete (6) and growth disadvantages persist in early childhood (5) . Through 24 months of life, even children exposed to HIV but uninfected (CHEU) have worse growth outcomes compared to children who are HIV unexposed and uninfected (CHUU, control children) (7) . Monitoring of long-term growth in HIV-affected children remains important to understand growth trajectory and to identify modifiable intervention.Stunting, a form of malnutrition that represents poor growth secondary to chronic protein-energy malnutrition (PEM), affects an estimated 144 million African children (8,9) .…”