Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia

Autor: Steven M. Albert, Daniel McClernon, Jeffrey J. Sevigny, Karen Marder, Leon G. Epstein, Michael P. McDermott, Ned Sacktor, G. Riggs, Katherine Conant, Karl Kieburtz, Ola A. Selnes, Donna Palumbo, Bruce A. Cohen, Giovanni Schifitto, Yaakov Stern, Justin C. McArthur
Rok vydání: 2004
Předmět:
Adult
Male
Macrophage colony-stimulating factor
AIDS Dementia Complex
Anti-HIV Agents
Human immunodeficiency virus (HIV)
HIV Infections
Neuropsychological Tests
medicine.disease_cause
Cohort Studies
Cognition
Predictive Value of Tests
Antiretroviral Therapy
Highly Active
medicine
Humans
Dementia
Life Tables
Cumulative incidence
Karnofsky Performance Status
Chemokine CCL2
Proportional Hazards Models
Intelligence Tests
Neurologic Examination
Tumor Necrosis Factor-alpha
business.industry
Incidence
Macrophage Colony-Stimulating Factor
Monocyte
Models
Immunological
Middle Aged
Viral Load
medicine.disease
CD4 Lymphocyte Count
Affect
medicine.anatomical_structure
Immunology
Cohort
HIV-1
Cytokines
Matrix Metalloproteinase 2
RNA
Viral
Female
Tumor necrosis factor alpha
Neurology (clinical)
business
Biomarkers
Immune activation
Zdroj: Neurology. 63:2084-2090
ISSN: 1526-632X
0028-3878
Popis: To evaluate whether baseline levels of plasma and CSF HIV RNA, tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), or macrophage colony stimulating factor (M-CSF) are predictors of incident HIV-associated dementia (HIVD) in a cohort with advanced HIV infection.A total of 203 nondemented subjects with CD4 lymphocyte counts less than 200/muL, or300/microL but with cognitive impairment, underwent semiannual neurologic, cognitive, functional, and laboratory assessments. HIVD and minor cognitive motor disorder (MCMD) were defined using American Academy of Neurology criteria. The cumulative incidence of HIVD was estimated using Kaplan-Meier curves. Cox proportional hazards regression models were used to examine the associations between biologic variables and time to HIVD, adjusting for age, sex, years of education, duration of HIV infection, type of antiretroviral use, premorbid IQ score, and presence of MCMD.After a median follow-up time of 20.7 months, 74 (36%) subjects reached the HIVD endpoint. The dementia was mild in 70% of cases. The cumulative incidence of HIVD was 20% at 1 year and 33% at 2 years. Highly active antiretroviral therapy (HAART) was used by 73% of subjects at baseline. A plasma HIV RNA level was undetectable in 23% of subjects and a CSF HIV RNA level was undetectable in 48% of subjects. In adjusted analyses, neither plasma nor CSF HIV RNA levels (log10) were associated with time to HIVD; log10 levels of plasma TNFalpha (HR 3.07, p = 0.03) and CSF MCP-1 (HR = 3.36, p = 0.06) tended to be associated with time to HIVD.The lack of association between baseline plasma and CSF HIV RNA levels and incident dementia suggests highly active antiretroviral therapy may be affecting CNS viral dynamics, leading to lower HIV RNA levels, and therefore weakening the utility of baseline HIV RNA levels as predictors of HIV-associated dementia.
Databáze: OpenAIRE
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