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

Abstract

Objective: To determine whether cerebral metabolite abnormalities normalize with highly active antiretroviral therapy (HAART).

Background: Patients with HIV-cognitive motor complex (HIV-CMC) show cerebral metabolite abnormalities in the early stages of dementia.

Methods: 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).

Results: 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).

Conclusions: 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].