Results. Both groups were comparable in regard to age (mean, 41 years for HIV-negative subjects and 39 years for HIV-positive subjects), sex (male sex, 14 [56%] of 25 HIVnegative subjects and 20 [77%] of 26 HIV-positive subjects), and education level (mean, 15 years for HIV-negative subjects and 16 years for HIV-positive subjects). HIV-positive subjects had a median CD4 cell count of 486 cells/mL and a median CD4 nadir of 278 cells/mL. Approximately 60% (15 of 26) of the HIV-positive subjects were receiving stable HAART regimens.
HIV-positive subjects had a lower baseline cerebral blood flow, compared with HIV-negative subjects. Increasing age and HIV infection caused statistically significant decreases in baseline cerebral blood flow, but no interaction occurred. For a given age, baseline cerebral blood flow values for HIV-positive subjects were equivalent to those for HIV-negative subjects who were 15 years older. Functional cerebral blood flow changes were also greater for HIV-positive subjects than for HIV-negative subjects. Both aging and HIV infection caused statistically significant increases in functional changes in cerebral blood flow, but no interaction was present. HIV infection was equivalent to a 21-year increase in brain age, compared with HIV-negative control subjects. Functional changes in the blood oxygen level-dependent signal were reduced for HIV-positive subjects, compared with HIV-negative subjects. Aging and HIV infection independently caused statistically significant decreases in functional blood oxygen level-dependent signal. Although the age-related regression lines intersected for the 2 groups, no statistically significant interaction was observed (P=.16). For a given age, functional changes in the blood oxygen level- dependent signal of HIV-positive subjects were equivalent to those of HIV-negative control subjects who were 15 years older.
Discussion. As the number of older HIV-positive individuals continues to increase, a growing need exists to understand the potential interactions between HIV and aging within the brain. Our results suggest that HIV infection and aging independently affect brain functional demands that are measurable by fMRI.
The lack of a synergistic interaction between age and HIV infection, although surprising, is comparable to the findings of a larger neuropsychological study that showed that age and HIV serostatus were independent risk factors for the development of HIV-associated neurocognitive disorders. Although our sample size was statistically significantly smaller than that in the previous descriptive study, our cohort included women, which may better reflect the diversity of the disease among the sexes.
Conflicting results concerning the relationship between HIV and aging have been noted in studies using structural neuroimaging. An interaction occurred in HAART-naive HIV-positive subjects observed using magnetic resonance spectroscopy, with a 5-fold increase present in frontal white matter inflammatory and glial metabolites. In contrast, diffusion tensor imaging of tissue water molecules did not show agedependent changes in HIV-positive subjects receiving stable HAART regimens. Discrepancies in these results could reflect differences in neuroimaging techniques or in the effects of HAART.