Abstract
Combination antiretroviral therapy (cART) limits human immunodeficiency virus (HIV) replication in the central nervous system (CNS) and prevents progressive neurological dysfunction. We examined if the degree of CNS penetration by cART, as estimated by the CNS penetration effectiveness (CPE) score, affects brain activity as measured by the amplitude of the blood oxygen level–dependent functional magnetic resonance imaging (BOLD fMRI) response. HIV+ patients on low-CPE cART (n=12) had a significantly greater BOLD fMRI response amplitude than HIV+ patients on high-CPE cART (n=12) or seronegative controls (n=10). An increase in the BOLD fMRI response in HIV patients on low-CPE cART may reflect continued HIV replication in the CNS leading to increased oxidative stress and associated metabolic demands.
Acknowledgements
This work was supported by the Center for AIDS Research (AI045008) (A.C.R., D.L.K., B.M.A.), the Center for Functional Neuroimaging (NS045839) (A.C.R., M.K.) at the University of Pennsylvania, the University of Pennsylvania AIDS Clinical Trials Unit (NIH AI 32783) (A.C.R., D.L.K., B.M.A.), a Universitywide AIDS Research Program Grant (CF05-SD-301) (B.M.A.), an American Foundation of AIDS Research (amFAR) (106729-40-RFRL) (B.M.A.), Dana Foundation for Brain and Immuno-Imaging (B.M.A.), and NIH grant (1K23MH081786) (B.M.A.). The authors would like to thank Drs. Ronald Ellis, Scott Letendre, and Richard Buxton for their helpful comments and insights. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.