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High Rates of Asymptomatic Neurocognitive Impairment in Vertically Acquired HIV-1-Infected Adolescents Surviving to Adulthood
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JAIDS Journal of Acquired Immune Deficiency Syndromes:
1 September 2010
Paramesparan, Yasotharan BSC; Garvey, Lucy J MBChB, MRCP; Ashby, Jane MBBS, MRCP; Foster, Caroline J BA, MBBS, MRCPCH; Fidler, Sarah BSc, MBBS, MRCP, PhD; Winston, Alan MBChB, MRCP, MD
*Division of Medicine, Imperial College London, W2 1PG, UK; Department of HIV Medicine, Imperial College Healthcare NHS Trust, London W2 1NY, UK; and à900 Clinic, Imperial College Healthcare NHS Trust, London W2 1NY, UK.
"This pilot study reveals high rates of asymptomatic NCI in perinatally infected HIV-positive young adults (67%) when compared with older subjects (19%). Such rates greatly exceed those observed in the cohorts of horizontally infected young adults, which we and others have assessed previously.10-12 Furthermore, these results may be an underestimation of true NCI prevalence in perinatally infected young adults..........our findings illustrate an area which requires urgent further research to evaluate and implement effective strategies to reduce NCI in chil dhood, adolescence, and young adulthood. HIV-associated NCI can adve rsely impact on ability to work or gain employment,13 adherence to medication, and quality of life.14-15 Clinicians should be aware of the presence of asymptomatic NCI in adolescents and young adults, regardless of disease stage."
To the Editors:
High rates of HIV encephalopathy and cognitive impairment are well described in infants and children with vertically acquired HIV infection. Despite reductions in incidence due to the availability and wider use of combination antiretroviral therapy, learning, behavioral, and motor deficits commonly persist.1-4 A high prevalence of neurocognitive and psychiatric morbidity in adolescents with a history of prior AIDS was recently reported,5 however, little is known regarding the cognitive function of neurologically asymptomatic, vertically infected children, surviving into adulthood without prior advanced disease. Such individuals will have undergone all stages of neurodevelopment and maturation in the presence of HIV infection and increasingly in the presence of antiretroviral agents with potential cerebral toxicities. We, therefore, undertook a pilot study to examine neurocognitive function in age-targeted c ohorts of younger and older HIV-infected adults to assess the frequency of neurocognitive impairment (NCI).
After obtaining informed consent from subjects, a detailed neurocognitive computerized assessment (Cogstate) was performed which tests multiple cognitive domains (including psychomotor function, executive function, memory, and attention) and has a high positive predictive value for detection of HIV-associated NCI.6 The International HIV Dementia Scale was also administered-a validated tool that incorporates timed finger tapping, sequential movement, and verbal recall.7 Subjects were required to be aged between 16 and 25 years (younger group), or greater than 60 years (older group). Exclusion criteria included a history of recreational drug misuse, active opportunistic infection, hepatitis C coinfection, or any neurological disease or symptoms. Demographic data including sex, age, education level (years), current and nadir plasma CD4+ cell count, time elapsed since HIV diagnosis, current antiretroviral drugs , and cerebrospinal fluid penetration effectiveness score8 were collected. Univariate linear regression modelling was used to investigate the presence of associations between computerized battery results and demographic data. The P values of <0.05 were considered statistically significant and parameters with a P value <0.1 entered into a multivariate model in a step-wise forward fashion using SPSS (Chicago, IL) version 16.0. NCI was defined as a score greater than 1 standard deviation poorer than an age-matched population dataset (data provided by the manufacturer) in at least 2 cognitive tasks.9 For subjects below 25 years, no age-matched population data exist and, therefore, results were compared with nearest-age matched controls (25-30 years).
Thirty-seven (6 younger and 31 older) HIV-infected individuals were recruited. The mean age of younger subjects was 18.8 years (range 17-23) and of older subjects was 65 years (range 60-77). Patient demographics are shown in Table 1. All subjects in the younger group had a history of vertically acquired HIV infection. All except 2 subjects (in the younger group) were receiving combination antiretroviral therapy and had an undetectable plasma HIV RNA level for a minimum of 3 months. Current mean plasma CD4+ cell count in the younger and older groups were 618 (SD 229) and 575 (SD 240) cells per microliter, respectively.
When compared with population data, 4 of 6 (66.7%) of younger subjects and 6 of 31 (19.4%) of older subjects met the diagnostic criteria for NCI. Using linear regression analysis, the presence of NCI was statistically significantly associated with younger age (P = 0.048, r = 0.33, 95%CI: -0.02 to -0.00) and younger versus older study group (P = 0.016, r = 0.39, 95%CI: 0.09 to 0.85). A trend toward higher rates of NCI and female gender was also observed although this did not reach statistical significance (P = 0.08, r = 0.293, 95%CI: -0.81 to 0.05). In a multivariate model, only younger study group remained statistically significantly associated with the presence of NCI. No other statistically significant associations were observed (P > 0.160 all cases, data not shown).
This pilot study reveals high rates of asymptomatic NCI in perinatally infected HIV-positive young adults (67%) when compared with older subjects (19%). Such rates greatly exceed those observed in the cohorts of horizontally infected young adults, which we and others have assessed previously.10-12 Furthermore, these results may be an underestimation of true NCI prevalence in perinatally infected young adults. Of approximately 57 young adults attending this dedicated adolescent HIV clinic, only 6 subjects were neurologically asymptomatic and elected to participate in the study. All had plasma CD4+ cell counts greater than 200 cells per microliter, and none had a history of prior AIDS events. It is likely these represent a motivated subgroup of patients, with an interest in their chronic disease and, therefore, by selection, are less likely to have gross NCI. Second, as no exact age-matched control data were available for the younger adults, an older (25-30 years) data reference group was utilized. Cognitive performance diminishes with age and therefore may also contribute to underestimation of NCI. Limitations of this study include the small sample size and incomplete virological suppression in 2 young subjects. Despite this, our findings illustrate an area which requires urgent further research to evaluate and implement effective strategies to reduce NCI in childhood, adolescence, and young adulthood. HIV-associated NCI can adversely impact on ability to work or gain employment,13 adherence to medication, and quality of life.14-15 Clinicians should be aware of the presence of asymptomatic NCI in adolescents and young adults, regardless of disease stage.
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