Effects of in utero antiretroviral exposure on longitudinal growth of HIV-exposed uninfected infants in Botswana

Abstract

Background: The impact of in utero exposure to highly active antiretroviral therapy (HAART) on longitudinal growth of HIV-uninfected infants is unknown.

Methods: The Mashi and Mma Bana PMTCT intervention trials enrolled HIV-infected pregnant women at four sites in Botswana. Breast-fed (BF), HIV-uninfected infants born at 37 weeks or greater were included in this analysis. Weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) z-scores were calculated using World Health Organization Child Growth Standards. Mean z-scores were compared between in utero antiretroviral exposure groups using Student t test, response profiles analysis, and general linear mixed effects modeling.

Results: Growth of 619 HAART-exposed and 440 zidovudine-exposed, HIV-uninfected infants was evaluated. Mean birth weights were 3.01 kg for HAART and 3.15 kg for zidovudine-exposed infants (P < 0.001) with lower mean birth WAZ, length-for-age (LAZ), and weight-for-length (WLZ) among HAART-exposed infants (all P < 0.001). HAART-exposed infants had greater improvement in WAZ and weight-for-length (WLZ) from birth through 2 months (P = 0.03, P < 0.001, respectively). The WAZ did not differ between groups from 3 through 6 months (P = 0.26). Length-for-age (LAZ) remained lower in HAART-exposed infants but the incidence of wasting or stunting did not differ between exposure groups.

Conclusions: Lower weights in HAART-exposed uninfected infants at birth were rapidly corrected during the first 6 months of life.

Trial registration: ClinicalTrials.gov NCT00197587 NCT00270296.

Conflict of interest statement

Potential conflicts of interest: No authors have a commercial or other association that might pose a conflict of interest (e.g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

Figures

Figure 1. Mashi and Mma Bana Mother-Infant Pair Antiretroviral Exposures for Breast Fed Infants

1 Beginning in Oct 2002, HAART became available through the national program. Women enrolled in the Mashi Study with CD4+ counts < 200 cells/mm3 were offered HAART. 2 In Aug 2002, as a result of efficacy data from a trial in Thailand, the peripartum intervention was revised to eliminate infant placebo and provide open label nevirapine to all infants to be given as a single dose within 72 hours of birth. 3 Infants in the ZDV exposure group remained on oral prophylactic ZDV up to a maximum of six months throughout the period of breast feeding. sdNVP = single dose nevirapine, ZDV = zidovudine, BF= breast feeding, 3TC = lamivudine, rtv = ritonavir

Figure 2

Study Eligibility

Figure 3

Response profile analysis modeling for mean infant z-scores by ARV exposure status