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Neruodevelopmental Outcomes in Preschool Children Living With HIV-1 Subtypes A and D in Uganda

Ruiseñor-Escudero, Horacio, PhD, MD, MSc*; Sikorskii, Alla, PhD*; Familiar-Lopez, Itziar, PhD, MPH, MD*; Persaud, Deborah, MD; Ziemniak, Carrie, MS; Nakasujja, Noeline, MD; Opoka, Robert, MD§; Boivin, Michael, PhD, MPH*

The Pediatric Infectious Disease Journal: December 2018 - Volume 37 - Issue 12 - p e298–e303
doi: 10.1097/INF.0000000000002097
HIV Reports

Background: HIV is a neuropathogenic virus that may result in detrimental neurodevelopmental (ND) outcomes early in life. This is the first study to evaluate the effect of HIV-1 subtype on neurodevelopment of Ugandan preschool children.

Methods: Neurodevelopment of 87 HIV-1 infected and 221 HIV exposed uninfected Ugandan children 1.8–4.9 years of age was assessed using 4 scales of the Mullen Scales of Early Learning (MSEL), 2 scales of the Color Object Association Test (COAT), and 1 score of the Early Childhood Vigilance Test. HIV-1 subtype was defined by phylogenetic analyses. General linear models were used to relate test scores to HIV-1 subtype (A versus D) while adjusting for relevant covariates. The scores were benchmarked against HIV exposed uninfected group to facilitate the interpretation.

Results: Seventy-one percentage of children infected with subtype A versus 60% of children with subtype D were currently on antiretroviral therapy (P = 0.49). Children with HIV-1 subtype A infection were older when compared with subtype D (3.29 vs. 2.76 years, respectively, P = 0.03), but similar regarding sex, socioeconomic status, weight-for-age z-score, CD4+ and CD8+ (% and total), viral load. No statistically significant differences by HIV-1 subtype were observed in the MSEL, COAT and Early Childhood Vigilance Test. Differences ≥ 0.33 of the SD were observed for the MSEL Composite Score, Receptive Language (MSEL) and Total Memory (COAT).

Conclusions: In contrast to previously reported differences in ND outcomes of school-age children by HIV-1 subtype, ND scores among preschool children were similar for subtypes A and D, with few potential differences on language production and memory outcomes that favored subtype A. Further investigation with larger sample sizes and longitudinal follow-up is needed.

From the *Department of Psychiatry, College of Osteopathic Medicine, Michigan State University, East Lancing, MI

Departments of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, MD

Makerere University, Department of Psychiatry, Kampala, Uganda

§Makerere University, Department of Pediatrics, Kampala, Uganda.

Accepted for publication April 7, 2018.

Clinical Trial Registration: Identifier NCT01640561.

All phases of this study were supported by the National Institutes of Health (NIH) grant# RO1 HD070723. HIV subtyping was supported by the Department of Psychiatry at Michigan State University.

The authors have no conflicts of interest to disclose.

Address for correspondence: Horacio Ruisenor-Escudero, PhD, MD, MSc, Department of Psychiatry, College of Osteopathic Medicine, Michigan State University, West Fee Hall, 909 Fee Rd., A322, East Lansing, MI 48824. E-mail:

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