We investigated the interactions between human immunodeficiency virus (HIV) infection and aging and their effects on brain function demands by means of functional magnetic resonance imaging (fMRI). A multiple-regression model was used to study the association and interaction between fMRI measures, HIV serostatus, and age for 26 HIV-infected subjects and 25 seronegative subjects. Although HIV serostatus and age independently affected fMRI measures, no interaction occurred. Functional brain demands in HIV-positive subjects were equivalent to those of HIV-negative subjects who were 15-20 years older. Frailty parallels between HIV infection and aging could result from continued immunological challenges depleting resources and triggering increased metabolic demands. In the future, fMRI could be a noninvasive biomarker to assess HIV infection in the brain.
Biological similarities exist between aging and human immunodeficiency virus (HIV) infection. Both cause a frailty phenotype characterized by generalized decreased physical function caused by enhanced vulnerability to immunological stressors and inflammatory dysregulation. The introduction of highly active antiretroviral therapy (HAART) has increased the population of older HIV-infected individuals (>50 years old). The physiological impacts of aging and HIV infection have been characterized within multiple organs but not within the brain.
Functional magnetic resonance imaging (fMRI) provides a noninvasive method to study brain metabolic demands. In control participants without HIV infection, aging decreases functional activity within certain brain regions while causing recruitment of additional structures. Statistically significant differences in functional brain activity occur in younger (<40 years old) HIV-infected subjects, compared with HIV-negative subjects. To date, no fMRI studies have investigated the possible interaction between HIV infection and aging. If fMRI is potentially to be used as a preclinical biomarker to assess HIV infection in the brain, then a broader spectrum of ages is required for studying both HIV-positive and HIV-negative subjects. Methods. HIV-negative (n=25) and HIV-positive (n=26) subjects (age, 20–62 years) provided written consent approved by the University of California, San Diego, institutional review board. A detailed medical history was obtained, and individuals were excluded if they had a previous history of other neurological illness or infections, cerebrovascular disease or strokes, major psychiatric disorders, or substance abuse 3 months prior to imaging. Subjects underwent imaging if reported substance abstinence was confirmed by negative urine toxicology test results. HIV-positive subjects either were not receiving HAART or had been receiving a stable regimen for >3 months. All HIV-positive patients had hematocrit levels, CD4 cell counts, and plasma HIV loads measured. The plasma HIV load was determined by reverse-transcription polymerase chain reaction (Amplicor; Roche Diagnostic Systems) using an ultrasensitive assay (lower quantification limit, <50 copies/mL). CD4 cell count nadir values were obtained by self-report or by direct measurement if the measured CD4 cell count was lower than the self-report measure.