Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity

Objective: Determine whether HIV and combination antiretroviral therapy (cART) affect resting-state functional connectivity (rs-fc) between the striatum and the cortical regions. Methods: Forty-nine HIV-uninfected (HIV-) and 132 HIV-infected (HIV+) (65% receiving cART) patients underwent laboratory studies (current and nadir CD4⁺ T-cell counts, and plasma HIV viral load), neuropsychological performance testing, and neuroimaging. Rs-fc, which examines the coordination of neural activity in distant brain regions, was used to investigate the cortico-striatal functional connections. The effect of cART was assessed comparing HIV+ individuals on cART (HIV+/cART+), and HIV+ individuals not currently receiving cART (HIV+/cART+). Relationships between laboratory tests, cognitive performance, and cART on subcortical-cortical rs-fc were assessed by an analysis of variance. Results: HIV+ individuals had lower cortico-striatal functional connectivity than HIV-controls, specifically between the striatum and the default mode network (P<0.001) and ventral attention network (P<0.001). HIV+/cART+ individuals had higher functional connectivity between the striatum, and default mode network (P=0.02) and ventral attention network (P=0.01), compared to the HIV+/cART- patients. Laboratory (current and nadir CD4⁺ T-cell counts, plasma viral load) and neuropsychological performance was not correlated with cortico-striatal rs-fc. Conclusions: HIV was associated with disrupted cortico-striatal networks, consistent with HIV's known impact on the subcortical areas. Interestingly, within certain networks, HIV+/cART+ individuals had similar rs-fc compared to HIV- controls, suggesting possible improvements in HIV-related neural dysfunction due to medications. Rs-fc may be a sensitive biomarker of neural insult and its recovery following cART. Additional studies may show rs-fc has utility in measuring acute inflammation caused by HIV.