Combination antiretroviral therapy modulates the blood oxygen level-dependent amplitude in human immunodeficiency virus-seropositive patients

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.