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  22nd Conference on Retroviruses and
Opportunistic Infections
Seattle Washington Feb 23 - 26, 2015
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Poor kidney function predicts neurocognitive
decline with undetectable viral load
  CROI 2015, February 23-26, 2015, Seattle, Washington
Mark Mascolini
An estimated glomerular filtration rate (eGFR) at or below 50 mL/min raised the odds of neurocognitive decline in a CHARTER cohort analysis of people with a 3-year undetectable plasma viral load [1]. Only 12% of study participants had falling cognitive function through 3 years of observation, and usually on only 1 of 15 tests.
Cognitive function may wane in HIV-positive people, even those taking suppressive antiretroviral therapy. One aim of the ongoing longitudinal CHARTER cohort study is to track rates of flagging cognitive function and to pinpoint risk factors by having cohort members complete 15 standard neuropsychological tests every 6 months. A recent analysis of 436 CHARTER members over an average 35 months recorded declines in 23%, stable function in 61%, and improved function in 17% [2].
The analysis presented at CROI focused on neurocognitive decline in all cohort members and in those with an undetectable plasma viral load through 3 years of follow-up. The CHARTER team defined neurocognitive deterioration as a drop of 0.5 standard deviation (SD) or more on at least 1 of the 15 tests in the first 36 months of follow-up. They used multiple logistic regression analysis to identify baseline sociodemographic, clinical, biological, and lifestyle factors associated with decline in people with a consistently undetectable viral load.
In the entire 701-person cohort, 1% or more cohort members had at least a 0.5 SD decline in only 5 of the 15 neuropsychological tests: grooved pegboard dominant (8% of participants), trail-making test B (5%), Wisconsin card-sorting test (2%), grooved pegboard nondominant (2%), and HVLT total learning (1%).
Of these 701 people, 191 (27%) maintained an undetectable plasma load through 3 years of follow-up. Twenty-three of those 191 people (12%) had evidence of cognitive decline during the 3 years, usually on only 1 neurocognitive test. Multivariate analysis identified four independent predictors of neurocognitive decline at the following adjusted odds ratios (aOR) (and wide 95% confidence intervals):
-- eGFR at or below 50 mL/min: aOR 6.80 (1.35 to 34.23)
-- HIV for 15 or more years: aOR 5.45 (1.19 to 25.02)
-- Education 12 years or fewer: aOR 4.25 (1.45 to 12.42)
-- Cerebrospinal fluid (CSF) protein above 45 mg/dL: aOR 3.25 (1.13 to 9.35)
The CHARTER team noted that the strongest predictor of ebbing cognitive function, low eGFR, is a known predictor of atherosclerotic vascular disease. But a history of cerebrovascular disease predicted waning cognitive function only in univariable analysis. Still, the researchers suggested that controlling cardiovascular risk factors such as falling kidney function--and notably smoking and obesity--"could be a useful strategy for minimizing cognitive decline." They observed that up to 80% of their study group reported either smoking or a body mass index at or above the obesity cutoff of 25 kg/m2.
The investigators called the association with high CSF protein an unexpected finding. Normal CSF protein stands between 15 and 45 mg/dL [3]. High CSF protein indicates inflammation and possibly inflammatory diseases such as meningitis or encephalitis [3]. The researchers also suggested it could reflect a more permeable blood-brain barrier.
Factors that predicted cognitive decline in previous studies but not in this analysis of people with an undetectable viral load include older age, current and nadir CD4 count, antiretroviral central nervous system penetration effectiveness score, hepatitis C coinfection, diabetes, hypertension, and an AIDS diagnosis.
In the 436-person published CHARTER analysis [2], predictors of neurocognitive decline were non-HIV-related comorbidities, lifetime psychiatric diagnoses, estimated premorbid IQ, and current hematocrit, albumin, total protein, aspartate aminotransferase; and depressive symptoms.
1. Brouillette MJ, Yuen T, Scott SC, et al. Predictors of neurocognitive decline among aviremic individuals in the CHARTER cohort. CROI 2015. February 23-26, 2015. Seattle, Washington. Abstract 469.
2. Heaton RK, Franklin DR Jr, Deutsch R, et al. Neurocognitive change in the era of HIV combination antiretroviral therapy: the longitudinal CHARTER study. Clin Infect Dis. 2015;60:473-480. http://cid.oxfordjournals.org/content/60/3/473.long
3. Agamanolis DP. Neuropathology. Chapter 14. Cerebrospinal fluid. http://neuropathology-web.org/chapter14/chapter14CSF.html