Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era
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Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system [CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART.
KeywordsCD4 nadir cortical volume duration of infection HAART HIV subcortical volume viral load
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- Alemán-Gómez Y. Melie-García L, Valdés-Hernández P. IBASPM: Toolbox for automatic parcellation of brain structures. In: Presented at the 12th Annual Meeting of the Organization for Human Brain Mapping. Florence, Italy: Available on CD-Rom in NeuroImage. June 11–15, 2006, Vol. 27, No.1.Google Scholar
- Burnham K, Anderson DR (2002). Model selection and multimodel inference: a practical-theoretic approach, 2nd ed. New York: Springer-Verlag.Google Scholar
- Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Yeni PG, Volberding PA (2000). Antiretroviral therapy in adults: updated recommendations of the International AIDS Society—USA Panel. JAMA 283: 381–390.PubMedCrossRefGoogle Scholar
- Gongvatana A, Schweinsburg BC, Taylor MJ, Theilmann RJ, Letendre SL, Alhassoon OM, Jacobus J, Woods SP, Jernigan TL, Ellis RJ, Frank LR, Grant I (2009). White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J NeuroVirol 15: 187–195.PubMedCrossRefGoogle Scholar
- Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ (2008). Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65: 65–70.PubMedCrossRefGoogle Scholar
- Paul RH, Ernst T, Brickman AM, Yiannoutsos CT, Tate DF, Cohen RA, Navia BA (2008). Relative sensitivity of magnetic resonance spectroscopy and quantitative magnetic resonance imaging to cognitive function among nondemented individuals infected with HIV. J Int Neuropsychol Soc 14: 725–733.PubMedCrossRefGoogle Scholar
- Paul RH, Yiannoutsos CT, Miller EN, Chang L, Marra CM, Schifitto G, Ernst T, Singer E, Richards T, Jarvik GJ, Price R, Meyerhoff DJ, Kolson D, Ellis RJ, Gonzalez G, Lenkinski RE, Cohen RA, Navia BA (2007). Proton MRS and neuropsychological correlates in AIDS dementia complex: evidence of subcortical specificity. J Neuropsychiatry Clin Neurosci 19: 283–292.PubMedCrossRefGoogle Scholar
- Valcour V, Sacktor N (2002). HIV-associated dementia and aging. J Ment Health Aging 8: 295–306.Google Scholar