Growing evidence points to persistent neurological injury in chronic HIV infection. It remains unclear whether chronically HIV-infected individuals on combined antiretroviral therapy (cART) develop progressive brain injury and impaired neurocognitive function despite successful viral suppression and immunological restoration. In a longitudinal neuroimaging study for the HIV Neuroimaging Consortium (HIVNC), we used tensor-based morphometry to map the annual rate of change of regional brain volumes (mean time interval 1.0 ± 0.5 yrs), in 155 chronically infected and treated HIV+ participants (mean age 48.0 ± 8.9 years; 83.9% male) . We tested for associations between rates of brain tissue loss and clinical measures of infection severity (nadir or baseline CD4+ cell count and baseline HIV plasma RNA concentration), HIV duration, cART CNS penetration-effectiveness scores, age, as well as change in AIDS Dementia Complex stage. We found significant brain tissue loss across HIV+ participants, including those neuro-asymptomatic with undetectable viral loads, largely localized to subcortical regions. Measures of disease severity, age, and neurocognitive decline were associated with greater atrophy. Chronically HIV-infected and treated individuals may undergo progressive brain tissue loss despite stable and effective cART, which may contribute to neurocognitive decline. Understanding neurological complications of chronic infection and identifying factors associated with atrophy may help inform strategies to maintain brain health in people living with HIV.
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http://dx.doi.org/10.1007/s13365-019-00723-4 | DOI Listing |
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Cyclin-dependent kinase 5 (CDK5), a unique member of the CDK family, is a proline-directed serine/threonine protein kinase with critical roles in various physiological and pathological processes. Widely expressed in the central nervous system, CDK5 is strongly implicated in neurological diseases. Beyond its neurological roles, CDK5 is involved in metabolic disorders, psychiatric conditions, and tumor progression, contributing to processes such as proliferation, migration, immune evasion, genomic stability, and angiogenesis.
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