Effects of in Utero Antiretroviral Exposure on Longitudinal Growth of HIV-Exposed Uninfected Infants in Botswana

Powis, Kathleen M MD, MPH*‡‖; Smeaton, Laura MS†; Ogwu, Anthony MB, BS‡; Lockman, Shahin MD, MSc‡§‖; Dryden-Peterson, Scott MD‡§‖; van Widenfelt, Erik BS§; Leidner, Jean MS†; Makhema, Joseph MB, ChB, MRCP§; Essex, Max DVM, PhD§‖; Shapiro, Roger L MD, MPH‖¶

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 February 2011 - Volume 56 - Issue 2 - pp 131-138
doi: 10.1097/QAI.0b013e3181ffa4f5
Clinical Science

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.

From the *Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; §Brigham and Women's Hospital, Infectious Disease Unit, Boston, MA; ∥Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA; and ¶Beth Israel Deaconess Medical Center, Boston, MA.

Received for publication July 21, 2010; accepted October 1, 2010.

Presented in part as Powis K, Smeaton L, Ogwu A, Lockman S, Dryden-Peterson S, van Widenfelt E, Leidner J, Makhema J, Essex M, Shapiro R. Impact of Highly Active Antiretroviral Therapy (HAART) and Short Course Zidovudine on Longitudinal Growth of HIV-Exposed Uninfected Breastfed Infants, Botswana at the 17th Conference on Retroviruses and Opportunistic Infections, February 2010, San Francisco, CA; Abstract 928; and Powis K, Smeaton L, Ogwu A, Lockman S, Dryden-Peterson S, van Widenfelt E, Leidner J, Makhema J, Essex M, Shapiro R. Impact of Highly Active Antiretroviral Therapy (HAART) and Short Course Zidovudine on Longitudinal Growth of HIV-Exposed Uninfected Breastfed Infants, Botswana at the NHASORC II-2010, Botswana, Oral Presentation 7.3B.

The Longitudinal Infant Growth Study was supported by a grant from the Harvard University Center for AIDS Research, the Global Infections Diseases Program, and the Global Health Scholars Program at the Harvard Institute for Global Health (K.M.P.). The Mashi study was supported by a grant from the National Institutes of Health, National Institute of Child Health and Human Development (R01 HD37793); a grant from the Oak Foundation; Boehringer Ingelheim (which provided nevirapine); by GlaxoSmithKline (which provided zidovudine); and the United Nations Children's Fund, which provided funds to assist with ongoing mentoring of the study participants. The Mma Bana study was supported by a grant (U01-AI066454) from the National Institute of Allergy and Infectious Diseases. The Fogarty International Center (TW00004) supported several study trainees for both the Mashi and Mma Bana studies. Funding support from Brigham and Women's Global Women's Health Fellowship supported K.M.P.'s salary during the Mma Bana study. Research grants from the National Institutes of Health: National Institute of Allergy and Infectious Diseases (UO1 AI066454) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (RO1 HD37793) support S.D.P.'s salary for the current study. Central CFAR Statistics Grant award #2P30AI060354-06 supported L.S.' salary for the current study.

Clinical Trials.gov Registration Numbers: NCT00197587 (Mashi) and NCT00270296 (Mma Bana).

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

Correspondence to: Kathleen M. Powis, MD, MPH, Department of Internal Medicine and Pediatrics, Massachusetts General Hospital, 175 Cambridge Street 5th Floor, Boston, MA (e-mail: kpowis@partners.org).

© 2011 Lippincott Williams & Wilkins, Inc.