Abstract
HIV-infected individuals (HIV+) have 2-3 times higher prevalence of tobacco smoking than the general U.S. population. This study aims to evaluate the independent and combined effects of tobacco-smoking and HIV-infection on brain microstructure and cognition using a 2 × 2 design. 21 HIV + Smokers, 25 HIV + Nonsmokers, 25 Seronegative (SN)-Smokers and 23 SN-Nonsmokers were evaluated using diffusion tensor imaging. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivity were assessed in 8 major cerebral fiber tracts and 5 subcortical regions. Cognitive performance in 7 neurocognitive domains was also assessed. Compared to SN, HIV+ had higher AD in genu of corpus callosum (GCC, p = 0.002). Smokers also had higher diffusivities in GCC, splenium of corpus callosum (SCC), anterior corona radiata (ACR), sagittal stratum (SS) and superior fronto-occipital fasciculus (SFO), than Nonsmokers (p-values<0.001-0.003). Tobacco-Smoking and HIV-infection showed synergistic effects on AD_SS (p = 0.002) and RD_SFO (p = 0.02), but opposite effects in FA_putamen (p = 0.024). Additive effects from HIV+ and Tobacco-Smoking were observed in 9 other white matter tracts, with highest diffusivities and lowest FA in HIV + Smokers. Higher diffusivities in the GCC, SCC, ACR and SS predicted poorer cognitive performance across all participants (p ≤ 0.001). Higher AD_GCC also predicted slower Speed of information processing and poorer Fluency and Attention only in HIV + Smokers (p = 0.001-0.003). Chronic tobacco smoking and HIV-infection appear to have additive and synergistic adverse effects on brain diffusivities, suggesting greater neuroinflammation, which may contribute to poorer cognition. Therefore, chronic tobacco-smoking may be a risk factor for HIV-associated neurocognitive disorders. Graphical Abstract ᅟ.