Objective: To determine if changes in brain metabolites are observed during early HIV infection and correlate these changes with immunologic alterations.Methods: Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10 chronically HIV-infected subjects without neurologic impairment underwent 1 H magnetic resonance spectroscopy. Subjects with early stage infection were identified near the time of HIV seroconversion and imaged within 60 days of an evolving Western blot, while still having detectable plasma virus. Subjects had blood drawn for viral RNA and T cell quantification.Results: Both N-acetylaspartate (NAA) and Glx (glutamate ϩ glutamine) were decreased in the frontal cortical gray matter of seropositive subjects. NAA levels were found to be decreased in the centrum semiovale white matter of chronically HIV-infected subjects, but not in those with early infection. Both HIV-infected cohorts demonstrated a lower number of CD4 ϩ T lymphocytes and a higher number of CD8 ϩ T lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects with early infection were associated with an expansion of CD8 ϩ T cells, especially effector CD8 ϩ T cells. Conclusions: These results verify metabolism changes occurring in the brain early during HIVinfection. Lower NAA and Glx levels in the cortical gray matter suggests that HIV causes neuronal dysfunction soon after infection, which correlates to the expansion of CD8 ϩ T cells, specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy to track NAA levels may provide important information on brain metabolic health while allowing better understanding of the virus-host interactions involved in CNS functional deficits. Neurology ® 2009;72:1465-1472 GLOSSARY APC ϭ allophycocyanin; Cho ϭ choline; Cr ϭ creatine; CTL ϭ cytotoxic T lymphocyte; Cy5.5 ϭ cyanin 5.5; FITC ϭ fluorescein isothiocyanate; FOV ϭ field of view; Glx ϭ glutamate ϩ glutamine; MI ϭ myoinositol; MRS ϭ magnetic resonance spectroscopy; NAA ϭ N-acetylaspartate; NRTI ϭ nucleoside reverse transcriptase inhibitors; PE ϭ phycoerythrin; PerCP ϭ peridinium chlorophyll protein; PHI ϭ primary HIV infection; SIV ϭ simian immunodeficiency virus; TE ϭ echo time; TI ϭ inversion time; TR ϭ repetition time.