Additive Effects of HIV and Chronic Methamphetamine Use on Brain Metabolite Abnormalities

Abstract

Objective-Proton magnetic resonance spectroscopy ( 1 H-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-1 H-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.Address correspondence and reprint requests to Dr. Chang, Department of Medicine, John A. Burns School of Medicine, University of Hawaii, 1356 Lusitana St., 7th Floor, Honolulu, HI 96813; LChang@hawaii.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptMethamphetamine, a psychostimulant with reinforcing effects similar to those of cocaine (1), has re-emerged as a major drug of abuse worldwide and is commonly used among HIVinfected individuals. In Thailand, both inhalation and injection of methamphetamine are associated with higher risk for HIV infection (2). Similarly, studies and large surveys in the United States (California and New York) consistently found that even noninjection methamphetamine use contributes to higher rates of unprotected sexual activity in both men and wo...

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