March 29, 2017
HIV-positive men responding well to antiretroviral therapy (ART) had significantly lower cerebral blood flow than a similar group of HIV-negative men, according to results of a cross-sectional comparison. Cerebral blood flow was not associated with cognitive impairment in this Dutch AGEhIV Cohort analysis.
AGEhIV is an ongoing study of middle-aged and older HIV-positive people in the Netherlands and an HIV-negative control group selected to match the HIV group sociodemographically. The AGEhIV investigators who conducted this study note that cognitive impairment persists in HIV populations despite viral control with ART. White matter hyperintensities detected by neuroimaging correlate with cognitive decline, and these white matter changes are associated with declining cerebral blood flow.
To assess possible associations between these variables, AGEhIV investigators conducted this cross-sectional comparison of HIV-positive and sociodemographically similar HIV-negative men 45 years or older. All HIV-positive men had maintained a viral load below 40 copies/mL for at least 12 months on ART. Study participants could not have past or current neurological disorders. All men completed standardized demographic, lifestyle and medical questionnaires and had full neuropsychological assessments covering six cognitive domains. Participants underwent MRI, which allowed calculation of cerebral blood flow.
The analysis included 100 men with HIV and 69 HIV-negative men with respective median ages of 54 and 53 years. Men with HIV smoked more than the comparison group (19.8 versus 8.0 pack-years, P = .01), but a higher proportion of HIV-negative men used ecstasy (12% versus 2%, P = .02). The groups did not differ significantly in prevalence of major comorbid conditions or use of antilipid drugs or psychotropics. Markers of inflammation (C-reactive protein) and immune activation (soluble CD14) were significantly higher in men with HIV. Men with HIV had been diagnosed for a median of 13.4 years and had taken ART for a median of 11.4 years.
Cerebral blood flow was lower in men with than without HIV (44.0 versus 46.4 mL/100 g min, P = .06). Spatial analysis indicated that blood flow was decreased throughout brain gray matter. After adjustment for potential confounders, HIV infection was significantly associated with lower cerebral blood flow (P = .02), as were greater waist circumference (P = .02), ecstasy use (P = .04) and (in men with HIV) prior clinical AIDS (P = .04) and higher triglycerides (P = .005).
Seventeen of 100 men with HIV had cognitive impairment, and HIV infection was significantly associated with worse cognitive function (P = .04). But, after adjustment for age, MRI scanner type, ecstasy use and waist circumference, cerebral blood flow was not associated with cognitive function in men with HIV. Compared with HIV-negative men, HIV-positive men had significantly lower gray matter volume (median 661 versus 693 mL, P = .03). HIV positivity remained associated with lower cerebral blood flow after adjustment for gray matter volume, age, ecstasy use and waist circumference.
The investigators suggest that the association between prior clinical AIDS and decreased cerebral blood flow could reflect vascular injury resulting from compromised immune status or disease severity. "Such vascular insult," they propose, "may have developed particularly in the period between HIV infection and initiation of effective ART, when viral toxicity and immune activation were at their peak[.]" The link between high triglycerides and decreased cerebral blood flow, the authors surmise, suggests that lipid changes (including those induced by ART) may affect cerebral arteries and microcirculation. Lack of an association between cerebral blood flow and cognitive impairment could reflect the low prevalence of cognitive impairment in these men with HIV (17%) or difficulty in detecting a relationship because differences in cerebral blood flow were subtle in this population.
Mark Mascolini writes about HIV infection.
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