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IAS 2015: HIV+ People with Asymptomatic Cognitive Impairment More Likely to Develop Symptoms

People with HIV who showed evidence of asymptomatic neurocognitive impairment at study entry were nearly twice as likely to progress to symptomatic HIV-associated neurocognitive disorders than those with initially normal neuropsychological tests, according to research presented at the 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention last month in Vancouver.

While the prevalence of frank AIDS-related dementia has declined dramatically since the advent of effective combination antiretroviral therapy (ART), less severe HIV-associated neurocognitive disorders remain common among people living with HIV.

Sean Rourke from the University of Toronto and colleagues looked at the prevalence and progression of HIV-related neurocognitive problems among participants in the Ontario HIV Treatment Network Cohort Study.

HIV-associated neurocognitive disorder -- dubbed HAND -- includes 3 degrees of severity:

• Asymptomatic neurocognitive impairment: at least mild neuropsychological impairment in 2 or more domains but no decrease in everyday functioning;
• Mild neurocognitive disorder: at least mild neuropsychological impairment in 2 or more domains with at least mildly decreased everyday functioning;
• HIV-associated dementia: overall neuropsychological impairment of at least moderate severity and major decline in everyday functioning.

Studies indicate that approximately half of people living with HIV have some form of HIV-associated neurocognitive disorder, but asymptomatic impairment that can only be detected with specialized tests is most common (70%), the researchers noted as background. A recent study of the U.S. CHARTER cohort found that asymptomatic neurocognitive impairment is associated with a 2- to 6-fold increased risk for developing symptomatic HAND. The present study aimed to replicate and extend these results in a Canadian population.

This analysis included 679 adults receiving HIV care in Toronto who completed at least 2 annual neuropsychological assessments. More than 80% were men, 62% were white, the mean age was 45 years, and the mean education level was 14 years.

Most participants (83%) were taking combination ART and 72% had undetectable HIV viral load. While 45% had a current CD4 T-cell count above 500 cells/mm³, 58% had previously had a nadir or lowest-ever count below 200 cells/mm³ (an indication for an AIDS diagnosis). More than a quarter (27%) were diagnosed with depression, 29% were current cigarette smokers, 16% reported non-medical drug use and 17% reported heavy alcohol use. Medical comorbidities were common, including diabetes (7%), cardiovascular disease (15%), hypertension (17%), and chronic lung disease (21%).

Neuropsychological testing was performed annually using a brief battery that included measures of cognitive processing speed, attention/working memory, and learning/memory (WAIS-R Digit Symbol, Grooved Pegboard, WMS-III Spatial Span, and Hopkins Verbal Learning Test-Revised). Cognitive symptoms or deficits were assessed using the 4-item Medical Outcomes Study HIV Health survey cognitive functioning scale, which assesses difficulties with memory, attention, reasoning, and concentration during the past 4 weeks.

People with a global deficit score less that 0.5 were considered to have normal neurocognitive function, those with score of 0.5 to 2 were considered to have asymptomatic neurocognitive impairment or mild neurocognitive disorder depending on whether they also had self-reported cognitive symptoms, and everyone with a score over 2 was classified as having dementia.

Results

• At baseline 357 participants had normal neuropsychological tests, while 322 showed evidence of asymptomatic neurocognitive impairment.
• Over a median 34 months of follow-up, 143 participants (21%) experienced progression to symptomatic HAND.
• Participants who started with asymptomatic neurocognitive impairment were more likely to progress to symptomatic HAND than those with normal neurocognitive function at baseline (27% vs 15%, respectively).
• Participants with asymptomatic neurocognitive impairment at their first visit had a significantly shorter time to progression than those with normal tests at baseline (relative risk 1.9).
• In a multivariate analysis, participants with asymptomatic neurocognitive impairment at baseline were 1.8 times more likely than those with normal tests to experience earlier progression to symptomatic HAND (hazard ratio [HR] 1.79).
• Female sex (HR 1.58), depression (HR 1.87), current smoking (HR 1.73), and cardiovascular disease (HR 1.67) were also significantly associated with increased risk of progression.
• Higher education level and speaking English at home were significantly associated with lower risk of progression (HR 0.94 and 0.60, respectively), while undetectable plasma HIV viral load showed a trend toward a protective effect (HR 0.72; p=0.089).

"Asymptomatic neurocognitive impairment diagnosis is associated with increased risk of progression to symptomatic HAND (i.e., mild neurocognitive disorder or HIV-associated dementia)," the researchers concluded.

"Regular monitoring (and retesting) of persons with asymptomatic neurocognitive impairment may help to identify those who may progress with neuropsychological impairments," they suggested. "Treatment of cardiovascular risk factors and depression are important avenues for intervention and may delay the onset or progression of HAND."

8/20/15

Reference

SB Rourke, J Gill, A Rachlis, et al. Asymptomatic neurocognitive impairment (ANI) is associated with progression to symptomatic HIV-associated neurocognitive disorders (HAND) in people with HIV: results from The Ontario HIV Treatment Network (OHTN) cohort study. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Vancouver, July 19-22, 2015. Abstract WEPEB326.