Additive and Synergistic Cardiovascular Disease Risk Factors and HIV Disease Markers' Effects on White Matter Microstructure in Virally Suppressed HIV

Background: It is unclear whether intermediate to high cardiovascular disease (CVD) risk and HIV disease status may have additive (ie, independent statistical effects concomitantly tested) or synergistic effects on white matter microstructure and cognition in virally suppressed HIV-infected (HIV+) men relative to sex and age-matched controls. Setting: Tertiary health care observational cohort. Methods: Eighty-two HIV+ men (mean age 55 +/- 6 years, 10%-30% on various CVD drugs; 20% with previous CVD) and 40 HIV-uninfected (HIV-) men (none with previous CVD; 10%-20% on various CVD drugs) underwent diffusion tensor imaging and neuropsychological testing. A standard classification of intermediate to high CVD risk (CVD+ group) was based on the Framingham score >= 15% cutoff and/or a history of CVD. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified in 11 white matter tracts. Results: Within the HIV- group, the CVD+ group had lower FA (P= 0.03) and higher MD (P= 0.003) in the corona radiata and higher MD in the corpus callosum (P= 0.02) and superior fasciculi (P= 0.03) than the CVD- group. Within the HIV+ group, the CVD+ group had lower FA in the superior fasciculi (P= 0.04) and higher MD in the uncinate fasciculus (P= 0.04), and lower FA (P= 0.01) and higher MD (P= 0.03) in the fornix than the CVD- group. The fornix alterations were also abnormal compared with the HIV- groups. The HIV+ CVD+ was more likely to have HIV-associated dementia. Older age, antihypertensive use, longer HIV duration, and higher C-reactive protein associated with lower FA and higher MD. Higher blood CD4(+)lymphocyte count and CD4/CD8 ratio associated with higher FA and lower MD. Conclusions: In virally suppressed HIV, CVD risk factors have a mostly additive contribution to white matter microstructural alterations, leading to a different distribution of injury in HIV- and HIV+ persons with CVD. There was also evidence of a synergistic effect of CVD and HIV factors on the fornix white matter injury.