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Clinical Trial
. 2012;7(11):e49272.
doi: 10.1371/journal.pone.0049272. Epub 2012 Nov 16.

Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection

Napapon Sailasuta  1 , William Ross, Jintanat Ananworanich, Thep Chalermchai, Victor DeGruttola, Sukalaya Lerdlum, Mantana Pothisri, Edgar Busovaca, Silvia Ratto-Kim, Linda Jagodzinski, Serena Spudich, Nelson Michael, Jerome H Kim, Victor Valcour; RV254/SEARCH 010 protocol teams
Collaborators, Affiliations
Clinical Trial

Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection

Napapon Sailasuta et al. PLoS One. 2012.

Abstract

Objective: Single 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).

Methods: Brain 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.

Results: After 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.

Interpretation: We 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.

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Conflict of interest statement

Competing Interests: The authors have read the journal’s policy and have the following conflicts: SEARCH received a grant from Gilead. Antiretroviral therapy was supported by Gilead (Truvada®, Atripla®), Merck (Sustiva®, Isentress®) and Pfizer (Selzentry®). Monogram Biosciences supported the Trofile® test. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1
Figure 1. MRS voxel locations.
A) left frontal white matter; B) basal ganglia; C) midline frontal gray matter; D) occipital gray matter.
Figure 2
Figure 2. Metabolites demonstrating change associated with antiretroviral treatment.
Metabolites demonstrating change associated with antiretroviral treatment included those demonstrating decreased inflammation [Panels A (MI/Cr in Occipital Grey Matter) and B (CHO/Cr in Basal Ganglia)] and those demonstrating increased neuronal integrity [Panels C (NAA/Cr in Frontal Grey Matter), D (NAA/Cr in Frontal White Matter), and E (NAA/Cr in Occipital Grey Matter)].
See this image and copyright information in PMC

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