Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia

Abstract

To determine whether cerebral metabolite abnormalities normalize with highly active antiretroviral therapy (HAART). Patients with HIV-cognitive motor complex (HIV-CMC) show cerebral metabolite abnormalities in the early stages of dementia. Sixteen patients with HIV-CMC were evaluated before and after HAART, and compared with 15 HIV-negative healthy volunteers. Cerebral metabolite ratios and concentrations in the frontal lobe and basal ganglia were measured using proton MRS (1H MRS). In 14 of 16 patients who tolerated HAART, CD4 count increased by 133+/-101 cells/mm3 (p = 0.0003), HIV Dementia Scale score increased by 1.8+/-2.4 points (p = 0.02), and AIDS dementia complex (ADC) stage decreased by 0.54+/-0.54 points (p = 0.003). The initially increased choline/creatine (CHO/CR) reversed in the midfrontal cortex (-8.0%; p = 0.02) and in the basal ganglia (-14.7%; p = 0.01). The initially elevated myoinositol (MI)/CR and myoinositol concentration [MI] in the basal ganglia also decreased (MI/CR: -14.1%; p = 0.005; [MI]: 11.8%; p = 0.02), along with normalization of [MI] in the frontal white matter (11.4%; p = 0.05). Furthermore, the change in [MI] in the frontal white matter correlated with the change in CD4 count (r = -0.67, p = 0.03) and with the change in ADC stage (p = 0.04). HAART improves HIV-CMC in addition to systemic measures of HIV infection. 1H MRS detects improvement of brain injury measured by cerebral metabolites, particularly the glial marker [MI], in patients with early HIV-CMC after HAART. In addition, the degree of improvement in clinical severity of HIV-CMC is related to the degree of recovery with [MI].