Additive effects of HIV and chronic methamphetamine use on brain metabolite abnormalities

Objective: Proton magnetic resonance spectroscopy (H-1-MRS) showed decreased neuronal marker N- acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities. Method: H-1-MRS was performed in 68 HIV-positive subjects ( 24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [ SD= 2,788] and last use a mean of 4.9 months earlier [ SD= 6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects ( 36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [ SD= 16,850] and last use a mean of 6.3 months earlier [ SD= 7.8]; 39 with no history of drug abuse). Concentrations of N- acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia. Results: HIV- negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions ( - 9% in the basal ganglia, - 7% in the frontal white matter, and - 6% in the frontal gray matter), on creatine in the basal ganglia ( - 7%), and on myo-inositol in the frontal white matter (+11%). Conclusions: The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.