In 2010, 330,000 infants were born with HIV, predominantly due to mother-to-child transmission (MTCT), and 90% of these infants were born in Sub-Saharan Africa. The number has dropped considerably due to increasingly successful prevention of MTCT using combination (triple) antiretrovirals (ARVs). The HIV epidemic remains substantial in South Africa, with 30% infection in pregnant women presenting at South African antenatal clinics. The Western Cape Government has adopted the WHO recommended ?Option B+? treatment plan, which has the potential to reduce HIV MTCT to under 1%, and the MTCT rate has fallen considerably. However, it has been reported that HIV-exposed, uninfected infants experience neurodevelopmental delays relative to their unexposed peers. In this study, we propose to measure the effects of in utero and perinatal exposure to ART and HIV on the developing infant brain, using neuroimaging at 38 to 41 weeks gestational age (GA) and neurodevelopmental assessments at 9 and 19 months of age.
We aim to determine whether early clinical indicators, including both infant and maternal health, and neuroimaging of the neonatal brain are predictive of later neurodevelopmental outcomes, whether HIV and ART exposure affect infant neurodevelopment, and whether the duration of in utero ART exposure affects outcomes. We will recruit 210 pregnant women, 140 HIV-infected and 70 uninfected, attending the antenatal clinic at the Michael Mapongwana Community Health Centre in Khayelitsha. Infected mothers and infants are treated according to the ?Option B+? guidelines, so that their infants will have been exposed to ARVs in utero either since conception (70 infants) or after 12 weeks (70 infants), postnatally and longer if breast feeding. Infants will be tested with HIV-1 DNA PCR at birth, and every 3 months if breast feeding. At 38 to 41 weeks GA, the infants will undergo neuroimaging at the Cape Universities Body Imaging Centre, including structural imaging for brain morphometry, diffusion for brain connectivity, and spectroscopy for brain metabolism. Participants will be followed every three months, with general examinations and growth assessments of the infants, and maternal health assessments, including depression, feeding practices and ARV compliance. Comprehensive neurodevelopmental testing with the Griffiths Mental Development Scale will be done at 9 and 19 months at the KID-CRU at Stellenbosch University (SUN). Acquisition and analysis techniques will be developed jointly by the University of Cape Town (UCT) and Massachusetts General Hospital (MGH). This project extends a successful collaboration between Dr. Barbara Laughton (SUN), Dr. Ernesta Meintjes (UCT) and Dr. Andr van der Kouwe (MGH). The project will build leading-edge neonatal brain imaging capacity in Cape Town, with unique imaging sequences and hardware, and infant handling techniques developed locally for ethically imaging neonates without sedation. UCT and SUN students will be involved in developing and applying the imaging, cognitive testing and analysis techniques used in the study.

Public Health Relevance

Successful programs for the prevention of mother-to-child transmission (PMTCT) have resulted in a new population of HIV-exposed, uninfected children. Evidence suggests that neurodevelopment is delayed in these children relative to their unexposed peers and that they may be at increased risk of illness and mortality. In this project, we will evaluate the effects of in utero and perinatal exposure to antiretroviral drugs and HIV on the infant brain, using leading-edge neonatal magnetic resonance neuroimaging techniques and neurodevelopmental assessments. The project builds on existing collaboration between the Universities of Stellenbosch and Cape Town and the Massachusetts General Hospital. We hope that a better understanding of brain development in these infants will help to guide care and treatment strategies.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Russo, Denise
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Massachusetts General Hospital
United States
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Nwosu, Emmanuel C; Robertson, Frances C; Holmes, Martha J et al. (2018) Altered brain morphometry in 7-year old HIV-infected children on early ART. Metab Brain Dis 33:523-535