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Older Age, HIV, and Antiretrovirals Linked to Neurodegenerative Marker
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First International Workshop on HIV and Aging, October 4-5, 2010, Baltimore
Mark Mascolini
Older age, HIV infection, antiretroviral therapy, and greater CD4 recovery were all associated with higher levels of phosphorylated Tau (pTau), a marker of neurodegenerative disease, in a small study of people with and without HIV [1]. Higher pTau levels in cerebrospinal fluid (CSF) correlated with worse prospective memory (remembering to do things planned), but not with worse global neurocognitive functioning in people with HIV.
Tau, a microtubule-associated protein, plays an important role in maintaining the integrity of neurons. Abnormalities in Tau, including Tau phosphorylated at threonine 181 (pTau), are regarded as markers of neurodegenerative disease. Researchers from the University of California, San Diego compared pTau levels in 70 people with HIV and 23 people without HIV, all of whom agreed to lumbar puncture, comprehensive neurocognitive testing, standardized neuromedical assessment, and blood sampling. The investigators subdivided the HIV group into 53 people taking antiretrovirals and 17 untreated people.
The HIV group group was older than the HIV-negative group at a median age of 45 years versus 36 years (P = 0.004). Women made up half of the non-HIV group (52%), compared with 18% of the HIV-positive no-antiretroviral group and 11% of the HIV-positive antiretroviral group (P < 0.001). Respective proportions of Caucasian were 48%, 41%, and 74% (P = 0.02). HIV-negative people averaged 15 years of education, compared with 12 to 13 years in the HIV groups (P = 0.06).
People with HIV had been infected for a median of 12.9 years, and 51% had AIDS. Their median nadir CD4 count stood at 209 (352 in the no-antiretroviral group versus 146 in the antiretroviral-treated group, P = 0.01). Median current CD4 count measured 546 and was similar in the two HIV groups. The no-antiretroviral group had a higher plasma viral load (3.9 versus 1.7 log, or 8000 versus 50 copies, P < 0.001) and a higher CSF load (2.9 versus 1.7 log, or about 1000 versus 50 copies, P < 0.001).
The median pTau level for the entire study group was 45.4 pg/mL (interquartile range 32.4 to 60.0), and the HIV group had significantly higher pTau concentrations (P = 0.003). Older age was associated with higher pTau levels in the entire study group (r = 0.25, P = 0.03), and the correlation was strongest in the antiretroviral-treated group. For every year of life, pTau rose 0.5 pg/mL in people without HIV and 0.8 in people with HIV.
In the HIV group, higher pTau was associated with Caucasian race (t = 1.9, P = 0.07), detectable viral load in plasma (t = 2.6, P = 0.01), detectable viral load in CSF (t = 1.9, P = 0.06), and greater CD4-cell recovery (r = 0.31, P = 0.007). Multivariate analysis found associations between higher pTau and older age (P = 0.03), a bigger CD4 gain in people taking antiretrovirals (P = 0.05), and antiretroviral use (P = 0.06). Higher pTau levels correlated with worse prospective memory as measured by the Memory for Intentions Test (MIST) summary score (r = -0.25, P = 0.03), but not with worse global neurocognitive functioning (P > 0.10).
The investigators proposed that "understanding how age, antiretroviral use, and immune recovery damage neuronal microtubules will be important for developing strategies to protect prospective memory, which is strongly associated with worse everyday functioning outcomes."
Reference
1. Letendre S, Rosario D, Ellis RJ, Potter M, Woods SP. Higher levels of phosphorylated tau in CSF are associated with HIV infection, older age, antiretroviral use, and worse prospective memory. First International Workshop on HIV and Aging. October 4-5, 2010. Baltimore. Abstract LB_01.
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