In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana

Abstract

Objective To assess associations between in-utero triple antiretrovirals (cART) versus zidovudine (ZDV) monotherapy exposure and growth among HIV-uninfected children of HIV-infected women in Botswana. Design Secondary retrospective data analysis from two randomized intervention trials of mother-to-child HIV transmission prevention. Methods The Mashi and Mma Bana studies enrolled HIV-infected pregnant women, following their children through 24 months of age. This analysis includes singleton, full-term, HIV-exposed uninfected children. Mothers received cART or ZDV at least 2 weeks predelivery, and breastfed up to 6 months. Weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) z-scores were derived. Mean z-scores were compared by exposure group at 24 months (t-test, linear regression). Results Of 819 children, 303 were ZDV- and 516 cART-exposed in utero. Maternal median enrolment CD4+ was higher among ZDV versus cART-treated mothers (393 versus 324 cells/µl; P < 0.0001). Median duration of antepartum antiretroviral use was shorter among ZDV-treated women (5.7 versus 12.0 weeks; P < 0.0001). Median months breastfed were similar (5.9 and 6.0; P = 0.43). At 24 months, mean LAZ and WAZ were significantly lower among cART-exposed children (LAZ −1.01 versus −0.74; P = 0.003) (WAZ −0.53 versus −0.30; P = 0.002) in unadjusted analyses. Adjusting for maternal CD4+, viral load, enrolment site and maternal anthropometric measures, cART-exposed children had significantly lower LAZ and WAZ at 24 months (P = 0.0004 for both). Conclusion At 24 months, in-utero cART-exposed children had significantly lower LAZ and WAZ. Poor growth impacts childhood and adult mortality. These findings raise concerns for potential lasting health impacts among HIV-exposed uninfected children with in-utero cART exposure.

Linear Growth Faltering Among HIV-Exposed Uninfected Children

“…In a previous study we found HEU children exposed to cART in utero had lower length at birth compared with zidovudine monotherapy-exposed children. 30,31 The cross-sectional nature of the study has some limitations but we also note that the children sampled in this survey are likely more representative of the general HEU child population than other studies using secondary analyses of clinical trials and follow-up studies which often provide improved medical care and growth monitoring.…”

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

“…Recent evidence raises concerns about the safety of certain antiretroviral drugs used in pregnancy, including increased risk for adverse birth outcomes [3,7–16], problems with pediatric growth and neurodevelopment [17] and future risk of cancer [6, 18–20]. Also, HIV-exposed, uninfected (HEU) children have increased morbidity and mortality when compared with HIV unexposed, uninfected (HUU) children.…”

Optimizing Research Methods to Understand HIV-Exposed Uninfected Infant and Child Morbidity: Report of the Second HEU Infant and Child Workshop

“…Most ARVs currently used are considered non-teratogenic; however, short-, medium-, and long-term effects of ARV exposure beyond congenital anomalies are not well understood. Findings from Botswana shared at the workshop indicate that compared to HEU infants with in utero exposure to zidovudine monotherapy, HEU infants with triple ARV in utero exposure had significantly lower length-for-age at 24 months, even after adjusting for maternal disease severity (13). This is just one example of recent findings highlighting the urgent need for large scale pharmacovigilance and ARV safety surveillance that can accommodate the pace of expanding universal ART and inevitably changing regimens.…”