Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection

Abstract

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.

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

“…Additionally, Cho and Cho/Cr levels increased initially in all three ROIs at peak viremia, indicating macrophage infiltration, but then decreased below baseline by the fourth week. Another 2009 study [75] of patients with early HIV infection confirmed some of the findings of the Westmorland study [62], including a sharp decline of NAA in the frontal cortex that was significantly correlated with expansion of CD8+ T cells. Thus, neuronal injury occurs in the frontal cortex as early as 2 weeks following the initial infection with HIV, suggesting that an increase in NAA may serve as a surrogate marker for therapy effectiveness in early stage treatment regimens.…”

“…For example, Lentz et al [75] recently used factor analysis to analyze the metabolic variance in seven different regions of the brain as well as immunologic measures and cognitive dysfunction. As a result, several statistically significant surrogate markers emerged for prognosis and for therapeutic monitoring of patients with HIV infection.…”

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes

“…Proton ( 1 H) magnetic resonance spectroscopy (MRS) provides measures of specific metabolites that reflect different pathological processes. Numerous MRS studies of HIV have demonstrated abnormalities of the cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), and glutamate/glutamine (Glx) Schifitto et al, 2009a;Schweinsburg et al, 2005;Paul et al, 2007;Lentz et al, 2009). Decreased NAA is known to reflect neuronal injury or loss, whereas increased Cho and MI have been linked to proinflammatory processes, and a breakdown of cell membranes (Ross and Bluml, 2001).…”

Application of brain multi-b-value diffusion-weighted imaging (DWI) in adolescent orphans from AIDS families

“…Moreover, asymptomatic HIV infection, a group which is often neglected, is hardly taken into consideration in scientific research. 6,9,14,19 In this study, asymptomatic HIV-positive adolescent orphans, who were born with HIV owing to mother-to-child transmission, were scanned using DWI with multi-b-value. The immune system of infants was immature and immune system function was poor.…”

“…Although they are in the asymptomatic stage, their nervous system may have been attacked by HIV. Some scholars 6,14,[19][20][21] indicated that central nervous system has been involved in the course of HIV infection in the early stage of the disease. We hope to identify the damaged parts of the nervous system and make a prediction of opportunistic infections by analyzing apparent diffusion coefficient (ADC), distribution diffusion coefficient (DDC) and heterogeneity index (a) values.…”