# Differences in growth trajectories in breastfed HIV-exposed uninfected and HIV-unexposed infants in Kenya: An observational cohort study

## TL;DR

Breastfed HIV-exposed uninfected infants in Kenya show slower growth compared to unexposed infants, even with modern HIV treatments.

## Contribution

This study is one of the few to compare growth in breastfed HIV-exposed uninfected infants under updated ART and breastfeeding guidelines.

## Key findings

- CHEU had significantly slower weight-for-length and head circumference growth in the first two years.
- CHEU were more likely to be underweight from 9 to 24 months compared to CHU.
- Stunting prevalence increased with age, with nearly one-third of children stunted by 24 months.

## Abstract

Children who are HIV-exposed and uninfected (CHEU) are at increased risk for poor growth compared to children who are HIV-unexposed (CHU). There are limited data on growth among CHEU in the era of preferred dolutegravir-based antiretroviral therapy (ART) for pregnant and breastfeeding women living with HIV (WLWH). We aimed to compare child growth outcomes in the first two years of life between breastfed CHEU and CHU, and to examine maternal HIV factors associated with growth in CHEU.

We enrolled pregnant women in Kenya and followed them with their child to age 24 months. We measured anthropometry within 7 days of birth, at 3 and 6 weeks, and months 3, 6, 9, 12, 18, and 24. We compared length-for-age Z-scores (LAZ), weight-for-age Z-scores (WAZ), weight-for-length Z-scores (WLZ), head circumference-for-age Z-scores (HCZ), and mid-upper arm circumference-for-age Z-scores (MUAC), and stunting (LAZ < −2), underweight (WAZ < −2), and wasting (WLZ < −2) between groups using linear mixed effects or modified Poisson regression models adjusted for maternal age, education, depression, anemia, household wealth index, time-varying breastfeeding, time-varying food insecurity, parity, and child sex. Among 333 mother-child pairs with at least two child visits (CHEU = 171; CHU = 162), mothers of CHEU were older, less educated, and had lower wealth than mothers of CHU. Birth characteristics were similar between groups, with 9% preterm births and 6% low birthweight. All WLWH were on ART, 89.5% on dolutegravir–lamivudine–tenofovir, 76.6% initiating ART preconception, and 91.2% virally suppressed. The duration of breastfeeding was significantly shorter for CHEU than CHU (median 15 versus 17 months). CHEU had significantly lower LAZ at birth, 18- and 24-months than CHU. In multivariable analysis, growth trajectories for WLZ and HCZ were lower among CHEU than CHU in the first 24 months (interaction p = 0.001 and p = 0.009, respectively). There was no difference in trajectory in LAZ, WAZ, and MUACZ between groups. By 24 months, 31.5% of CHEU were stunted, 9.3% underweight, and 2.4% wasted, versus 27.2%, 3.2%, and 0.6% of CHU, respectively; only the difference in underweight prevalence was statistically significant. CHEU had a higher risk of being underweight from 9- to 24 months than CHU (adjusted Relative Risk at 24 months, 2.99 [95% CI: 1.08, 8.30]; p = 0.034). Growth was associated with maternal education, wealth, and breastfeeding and was lower among male infants. Among CHEU, maternal preconception ART was not associated with growth. Important limitations of this study include the possibility of unmeasured confounding and limited generalizability to contexts with differing prevalence of malnutrition, access to and uptake of ART, or breastfeeding practices.

Despite breastfeeding and optimal maternal dolutegravir-based ART, CHEU experienced growth deficits compared to CHU in the first two years of life. Continued monitoring of the expanding CHEU population is essential in the context of rapidly evolving guidelines and policies to optimize their health and to identify and prevent future health disparities and disease risks.

Children who are HIV-exposed and uninfected (CHEU) are at increased risk for poor growth compared to children who are HIV-unexposed (CHU).

In 2016, WHO extended the continued breastfeeding duration guidance for lactating women living with HIV (WLWH) adherent to antiretroviral therapy (ART) from 12 months to at least 24 months for those residing in countries that promote and support breastfeeding with ART.

The WHO now recommends dolutegravir (DTG)-based ART as the preferred first-line treatment for pregnant WLWH. However, few studies compare growth between CHEU and CHU in the context of updated ART guidelines and safer, sustained breastfeeding practices among WLWH.

We compared growth trajectories of breastfed Kenyan CHEU and CHU in the first two years of life. This is one of the few studies conducted in the context of universal ART and sustained breastfeeding, where most WLWH (90%) were on the WHO preferred first-line ART, DTG–lamivudine–tenofovir, during pregnancy.

Our findings show that CHEU had significantly slower weight-for-length and head circumference-for-age growth in the first 2 years, and were more likely to be underweight from 9 to 24 months than CHU. Stunting prevalence increased with age in this population, and by 24 months, nearly one-third of all children were stunted.

Our study highlights growth deficits, particularly poorer weight gain and slower weight-for-length growth among breastfed CHEU. These findings may reflect lasting metabolic or epigenetic effects from in utero exposure to ART. They underscore the need for further mechanistic research to elucidate biological pathways underlying poor growth outcomes among CHEU and to help guide the selection of the safest ARV regimens during pregnancy.

Continued growth monitoring is critical as HIV and ART guidelines evolve.

The main limitation of our study is its limited representativeness of the broader CHEU population, due to differences in access to ART during pregnancy and postpartum, duration of exclusive and sustained breastfeeding, and prevalence of child malnutrition. Consequently, additional population-based studies in diverse settings are needed to validate these findings.