TY - JOUR
T1 - Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection
AU - Sailasuta, Napapon
AU - Ross, William
AU - Ananworanich, Jintanat
AU - Chalermchai, Thep
AU - DeGruttola, Victor
AU - Lerdlum, Sukalaya
AU - Pothisri, Mantana
AU - Busovaca, Edgar
AU - Ratto-Kim, Silvia
AU - Jagodzinski, Linda
AU - Spudich, Serena
AU - Michael, Nelson
AU - Kim, Jerome H.
AU - Valcour, Victor
AU - Phanuphak, Nittaya
AU - Teeratakulpisarn, Nipat
AU - Fletcher, James L.K.
AU - Suttichom, Duanghathai
AU - Pinyakorn, Suteeraporn
AU - Rattanamanee, Somprartthana
AU - Chomchey, Nitiya
AU - Mangum, Peeriya
AU - Ubolyam, Sasiwimol
AU - Suwanwela, Nijasri C.
AU - Chaisinanunkul, Napasri
AU - Suthiponpaisan, Udom
AU - Sutthapas, Chumpita
AU - deSouza, Mark
AU - Ngauy, Viseth
AU - Trichavaroj, Rapee
AU - Akapirat, Siriwat
AU - Marovich, Mary
AU - Wendelken, Lauren
AU - Busovaca, Edgar
AU - Liu, Carol
AU - Mun, Elijah
AU - Miller, Bruce
N1 - Funding Information:
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.
PY - 2012/11/16
Y1 - 2012/11/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84869226441&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0049272
DO - 10.1371/journal.pone.0049272
M3 - Article
C2 - 23229129
AN - SCOPUS:84869226441
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e49272
ER -