Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

Abstract

ObjectiveSingle voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART).MethodsBrain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART.ResultsAfter adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months.InterpretationWe detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

Cerebral metabolite changes prior to and after antiretroviral therapy in primary HIV infection

“…A recent acute infection study has identified elevations of Cho/Cr in the basal ganglia at 14 days postexposure and its subsequent reduction to control levels with 6 months of ART. 29 The reduction of basal ganglia Cho/Cr in that study may be related to the earlier initiation of ART than in our study. It is also possible that this is a region-specific observation, as the study also noted a Cho/Cr elevation in the occipital gray matter at baseline that was not reduced upon ART initiation.…”

“…All individuals reported symptoms of acute HIV syndrome and 5 additionally reported severe headaches, numbness in extremities, and difficulty thinking clearly. 30 In predominantly less symptomatic acute infection studies, no significant differences in baseline NAA/Cr were identified, 10,29 though this may be limited by sample size. Similarly, we report no significant differences in baseline NAA/Cr in PHI as compared to HIV-uninfected controls, but low NAA/Cr in parietal gray matter trended toward significance (p 5 0.064).…”

“…30 Evidence for recovery of NAA/Cr is also reported in acute infection studies with increases (greatest in first months post infection) in NAA/Cr in frontal gray matter, frontal white matter, and occipital gray matter despite not detecting significant differences at baseline. 29 Furthermore, baseline NAA/Cr in basal ganglia was significantly elevated in Fiebig III/IV when compared to Fiebig I/II, 29 which provides additional context for a temporal relationship of recovering NAA/Cr. We detected increases of NAA/Cr in the ART-naive condition, which implies that NAA/Cr recovery in early infection may not be dependent on ART, and hypothesize that the lack of significance in ART-initiated slope can be attributable to the later timeframe rather than the effect of therapy.…”

Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline

“…In Table 2 Adjusted relative risk for symptomatic progression: Asymptomatic neurocognitive impairment vs neurocognitively normal addition, neuroimaging studies find detectable structural, functional, and spectroscopic evidence of brain abnormalities even in the acute and early phases of HIV infection. [21][22][23][24][25] Of interest, those with ANI at baseline had evidence of more advanced prior HIV disease, e.g., lower nadir CD4 and greater likelihood of an AIDS diagnosis. This finding supports the concept that ANI is an HIV-driven process that, like more severe forms of HAND, is more likely with greater levels of prior immunosuppression.…”

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy

“…Furthermore, markers of immune activation may reflect the degree of viral load and neurocognitive impairment [16]. Magnetic resonance spectroscopy (MRS), a noninvasive quantitative MR technique that measures alterations in cerebral metabolite levels, demonstrates that inflammatory cerebral metabolites are elevated in acute HIV infection (ie, the period before antibody seroconversion) and longitudinally increased over time in PHI before cART initiation [1,17,18]. Thus, crucial processes during the primary phase of viral infection may underlie the initiation of HIV-associated CNS injury.…”