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HIV Viremia During Pregnancy and Neurodevelopment of HIV-Exposed Uninfected Children in the Context of Universal Antiretroviral Therapy and Breastfeeding

A Prospective Study

le Roux, Stanzi M., MBChB, MPH*; Donald, Kirsten A., FCPaed, PhD†,‡; Kroon, Max, FCPaed†,§; Phillips, Tamsin K., MPH*,¶; Lesosky, Maia, PhD*; Esterhuyse, Liza, MA*; Zerbe, Allison, MPH; Brittain, Kirsty, MPH*,¶; Abrams, Elaine J., MD‖,**; Myer, Landon, MBChB, PhD*,¶

The Pediatric Infectious Disease Journal: January 2019 - Volume 38 - Issue 1 - p 70–75
doi: 10.1097/INF.0000000000002193
HIV Reports

Background: Elevated HIV viral load (VL) in pregnancy has been linked to increased risk of mortality, immunologic abnormalities, infectious morbidity and restricted growth among HIV-exposed uninfected (HEU) children, but little is known about effects on child development.

Methods: HIV-infected women initiating lifelong antiretroviral therapy (ART; tenofovir + emtricitabine + efavirenz) antenatally were followed from first antenatal visit through delivery and with their breastfed infants postpartum. Cognitive, motor and expressive language development (Bayley Scales of Infant and Toddler Development-Third Edition; delay defined as score <85) were assessed on a subset of HEU infants. HIV VL was measured at ART initiation, in third trimester and around delivery. Cumulative viremia in pregnancy was expressed as log10 VL copies × year/mL [viremia copy-years (VCY)]. Relationships between VCY and development were examined after adjusting for socioeconomic, behavioral and psychosocial confounders.

Results: Women (median pre-ART log10 VL 4.1, CD4 349 cells/mm3) commonly reported adverse social circumstances (44% informal housing, 63% unemployed, 29% risky drinking). Among 214 infants (median age, 13 months; 53% male; 13% born <37 weeks’ gestation), viremia predicted lower motor and expressive language, but not cognitive, scores in crude and adjusted analysis [per log10 VCY increase, αβ (95% confidence interval [CI]): motor, −2.94 (−5.77 to −0.11); language, −3.71 (−6.73 to −0.69) and cognitive −2.19 (−5.02 to 0.65)]. Increasing VCY also predicted higher relative odds of motor delay [adjusted odds ratio (aOR): 3.32; 95% CI: 1.36–8.14) and expressive language delay (aOR: 2.79; 95% CI: 1.57–4.94), but not cognitive delay (aOR: 1.68; 95% CI: 0.84–3.34).

Conclusions: Cumulative maternal HIV viremia in pregnancy may have adverse implications for HEU child development.

From the *Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine

Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa

Division of Developmental Paediatrics, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa

§Neonatal Service, Mowbray Maternity Hospital, Cape Town, South Africa

Centre for Infectious Disease Epidemiology and Research (CIDER), School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa

ICAP at Columbia, Mailman School of Public Health

**College of Physicians and Surgeons, Columbia University, New York, New York.

Accepted for publication August 23, 2018.

This research was supported by PEPFAR (President's Emergency Plan for AIDS relief) through NICHD Eunice Kennedy Shriver National Institute of Child Health and Human Development under Cooperative Agreement 1R01HD074558. Additional funding comes from the Elizabeth Glaser Pediatric AIDS Foundation, South African Medical Research Council, the Fogarty Foundation (National Institutes of Health Fogarty International Center Grant No. 5R25TW009340) and the Office of AIDS Research.

The authors have no conflicts of interest to disclose.

S.M.l.R. assisted with collection of data, conducted the analysis and wrote the first draft of the manuscript. K.A.D. provided training and supervision of developmental assessments; K.A.D. and M.K. provided supervision for all child health aspects of the study. L.M. and E.J.A. conceived the Maternal and Child Health Antiretroviral Therapy (MCH-ART) study and were responsible for study design, funding, implementation and overall leadership. T.K.P. was the study coordinator. T.K.P. and K.B. were responsible for data management and oversight. L.E. conducted developmental assessments and assisted with data management. M.L. contributed to the data analysis. A.Z. was the senior study manager and provided oversight of all study administration processes. All authors contributed to and approved the final manuscript.

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Address for correspondence: Stanzi M. le Roux, MBChB, MPH, Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, Health Sciences Faculty, University of Cape Town, Falmouth Building Entrance 5 Level 5, Medical Campus, Anzio Road, 7935 Cape Town, South Africa. E-mail:

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