https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60555-2.pdf

Inequality in early childhood: risk and protective factors for early child development

BACKGROUND: We reviewed the impact of HIV, HIV exposure, and antiretroviral therapy/prophylaxis on neurodevelopmental outcomes of HIV-infected and HIV-exposed-uninfected infants and children. METHODS: A literature search of Medline, Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990–March 2011) using the search terms, infant, child, HIV, neurodevelopment, cognition, language, and antiretroviral therapy, identified 31 studies of HIV/antiretroviral exposure using standardized tools to evaluate infant/child development as the main outcome. Articles were included if results were reported in children RESULTS: Infants who acquired HIV during fetal and early life tended to display poorer mean developmental scores than HIV-unexposed children. Mean motor and cognitive scores were consistently 1 to 2 SDs below the population mean. Mean scores improved if the infant received treatment before 12 weeks and/or a more complex antiretroviral regimen. Older HIV-infected children treated with highly active antiretroviral therapy demonstrated near normal global mean neurocognitive scores; subtle differences in language, memory, and behavior remained. HIV-exposed-uninfected children treated with antiretrovirals demonstrated subtle speech and language delay, although not universally. CONCLUSIONS: In comparison with resource-rich settings, HIV-infected and HIV-exposed-uninfected infants/children in resource-poor settings demonstrated greater neurodevelopmental delay compared with HIV-unexposed infants. The effects on neurodevelopment in older HIV-infected children commenced on antiretroviral therapy from an early age and HIV-exposed-uninfected children particularly in resource-poor settings remain unclear.

Neurodevelopment in Children Born to HIV-Infected Mothers by Infection and Treatment Status

Globally, an estimated 3.4 million children are living with HIV, yet little is known about the effects of HIV and antiretroviral treatment (ART) on the developing brain, and the neurodevelopmental and behavioural outcomes of perinatally HIV-infected (PHIV+) adolescents. We reviewed the literature on neurodevelopmental outcomes in PHIV+ children and adolescents, and summarized the current evidence on behaviour, general cognition, specific domains, hearing and language, school performance and physical disabilities due to neurological problems. Evidence suggests that PHIV+ children do not perform as well as controls on general cognitive tests, processing speed and visual-spatial tasks, and are at much higher risk for psychiatric and mental health problems. Children with AIDS-defining diagnoses are particularly at risk for poorer outcomes. A striking finding is the lack of published data specific to the adolescent age group (10-25 years), particularly from resource-constrained countries, which have the highest HIV prevalence. In addition, extreme heterogeneity in terms of timing and source of infection, and antiretroviral experience limits our ability to summarize findings of studies and generalize results to other settings. Due to the complex nature of the developing adolescent brain, environmental influences and variation in access to ART, there is an urgent need for research on the longitudinal trajectory of neurodevelopment among children and adolescents perinatally infected with HIV, especially in high burden resource-constrained settings.

https://onlinelibrary.wiley.com/doi/pdf/10.7448/IAS.16.1.18603

Neurodevelopment in perinatally HIV-infected children: a concern for adolescence

OBJECTIVES: To evaluate the effect of early versus deferred antiretroviral therapy (ART) on the neurodevelopment of infants from Cape Town participating in the Children with HIV Early Antiretroviral Therapy (CHER) trial. DESIGN: HIV-infected infants were randomized to early (<3 months) or deferred ART. HIV-uninfected infants (HIV-exposed and HIV-unexposed) provide background data. METHODS: Neurological examination and Griffiths Mental Development Scales (GMDS) were administered between 10-16 months of age by testers blind to HIV status and randomized allocation. Mean quotients were compared using paired Students t-tests. RESULTS: Sixty-four infants on early ART and 26 on deferred ART (of potential 77 and 38 respectively on CHER trial) were assessed at median age 11 months (range 10-16). On the GMDS all scores were lower in the deferred arm and the General Griffiths and Locomotor Scores were significantly lower: mean (SD) =100.1 (13.8) vs. 106.3 (10.6) P=0.02; and 88.9 (16.3) vs. 97.7 (12.5) P<0.01 respectively. Children with HIV who received early ART performed as well as children without HIV except on the Locomotor subscale. Both infected and uninfected mean GMDS scores were within the average range. CONCLUSION: Infants initiated on early ART have significantly better Locomotor and general scores on the GMDS at median age 11 months compared to infants on deferred ART despite careful monitoring and ready access to ART in the latter. (c) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Early antiretroviral therapy improves neurodevelopmental outcomes in infants

OBJECTIVE: Because antiretroviral treatment (ART) fails to improve neurocognitive impairment in children with HIV we completed a pilot study evaluating the feasibility and cognitive benefit of computerized cognitive rehabilitation therapy (CCRT) in Ugandan children with HIV. METHOD: Sixty Ugandan children with HIV (23 on ART) were randomly assigned to 10 sessions of Captains Log CCRT (Sandford 2007) training configured for attention and memory skills or no intervention. Kaufman Assessment Battery for Children (2nd ed. KABC-2; Kaufman & Kaufman 2004) performance at baseline indicated pervasive neurocognitive impairment. Cognitive ability was assessed before and after training using the Cogstate computerized neuropsychological test (Darby Maruff Collie & McStephen 2002). Viral load along with CD4 and CD8 absolute and activation levels also were measured posttest. RESULTS: CCRT was well received with a 95% adherence rate to scheduled training sessions. CCRT intervention children showed greater improvement on a Cogstate card detection task of simple attention (p = .02) and speed of correct moves on a Groton Maze Learning Task (p < .001). These analyses were completed using an analysis of covariance model that adjusted Cogstate performance for the childs age standardized weight for age gender socioeconomic status school grade level and baseline KABC-2 performance. ART treatment was not related to Cogstate performance or improvement as a result of CCRT. CD4 and CD8 activation levels were correlated with Cogstate improvement specifically for the CCRT group. CONCLUSIONS: CCRT was feasible with our study population and improved maze learning and attention on a detection task. This supports previous findings by our group with cerebral malaria survivors (Bangirana Giordani et al. 2009). Copyright 2010 APA all rights reserved.

A pilot study of the neuropsychological benefits of computerized cognitive rehabilitation in Ugandan children with HIV.

Results: At enrolment, the mean (±SD) age was 60±46 months, 17 (44%) and 22 (56%) had Centers for Disease Control (CDC) clinical category B and C disease respectively, and 36 (92%) had severe immunosuppression. At the start of HAART no child had cranial nerve or cerebellar dysfunction, but 13/29 (33.3%) had evidence of motor dysfunction. By 6 months 1 child had developed cerebellar dysfunction, but there was no statistically significant change in the frequency of motor dysfunction. Mean baseline performances on cognitive testing were generally subnormal. Between 33% and 81% of the children recorded subnormal intelligence quotients on various cognitive tests. Mean performances did not change significantly after 6 months of HAART. Conclusion: Neurological and neurocognitive deficits are frequent in HIV-infected children. The prevalence and extent of deficits did not change significantly in response to short-term HAART, indicating neither spontaneous improvement nor deterioration during early treatment.

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Lara Smith

Papers

Neurological and neurocognitive function of HIV-infected children commenced on antiretroviral therapy