Five year neurodevelopment outcomes of perinatally HIV-infected children on early limited or deferred continuous antiretroviral therapy.

Journal: Journal of the International AIDS Society

Volume: 21

Issue: 5

Year of Publication: 2019

Affiliated Institutions:  Family Clinical Research Unit, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa. Centre for Infectious Disease Epidemiology and Research, and Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, University of Stellenbosch, Matieland, South Africa. Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom.

Abstract summary 

Early antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV-infected (HIV-positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long-term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV-infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART-Def); immediate time-limited ART for 40 weeks (ART-40W) or 96 weeks (ART-96W). ART was restarted in the time-limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants.A prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery-Buktenica developmental tests for visual motor integration at 60 months. HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms.In this study, 28 ART-Def, 35 ART-40W, 33 ART-96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART-Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV-infected children (mean standard scores: 75.8 ART-Def, 79.8 ART-40W, 75.9 ART-96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)).Early locomotor delay in the ART-Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV-infected children on early time-limited ART were similar to uninfected controls, apart from visual perception where HIV-infected children scored lower. Poorer visual perception performance warrants further investigation.

Authors & Co-authors:  Laughton Barbara B Cornell Morna M Kidd Martin M Springer Priscilla Estelle PE Dobbels Els Françoise Marie-Thérèse EFM Rensburg Anita Janse Van AJV Otwombe Kennedy K Babiker Abdel A Gibb Diana M DM Violari Avy A Kruger Mariana M Cotton Mark Fredric MF

Study Outcome 

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Statistics
Citations :  Patel K, Ming X, Williams PL, Robertson KR, Oleske JM, Seage GR III, et al. Impact of HAART and CNS‐penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents. AIDS. 2009;23(14):1893–901.
Authors :  12
Identifiers
Doi : e25106
SSN : 1758-2652
Study Population
Male,Female
Mesh Terms
Anti-HIV Agents
Other Terms
ARV;CHER trial;Children;Early time-limited antiretroviral therapy;Griffiths mental development scales;HIV care continuum;Neurodevelopment;Treatment interruption;Visual perception
Study Design
Randomized Control Trial,Longitudinal Study,Cross Sectional Study
Study Approach
Mixed Methods
Country of Study
Publication Country
Switzerland