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.

Trial registration: ClinicalTrials.gov NCT00197587 NCT00270296.

Figures

Fig. 1. Study consort diagram

Fig. 2. Mean anthropometric measures over time by exposure group ZDV exposure group n = 303; cART exposure group n = 516

Horizontal dotted value line represents a z-score value of zero.