TY - JOUR
T1 - HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Naïve Patients
AU - Valcour, Victor G.
AU - Ananworanich, Jintanat
AU - Agsalda, Melissa
AU - Sailasuta, Napapon
AU - Chalermchai, Thep
AU - Schuetz, Alexandra
AU - Shikuma, Cecilia
AU - Liang, Chin Yuan
AU - Jirajariyavej, Supunee
AU - Sithinamsuwan, Pasiri
AU - Tipsuk, Somporn
AU - Clifford, David B.
AU - Paul, Robert
AU - Fletcher, James L.K.
AU - Marovich, Mary A.
AU - Slike, Bonnie M.
AU - DeGruttola, Victor
AU - Shiramizu, Bruce
PY - 2013/7/31
Y1 - 2013/7/31
N2 - Objectives:Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14+ enriched monocytes predicted cognitive impairment and brain injury.Methods:We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14+ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).Results:The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14+ HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14+ HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.Interpretation:Reservoir burden of HIV DNA in monocyte-enriched (CD14+) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.
AB - Objectives:Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14+ enriched monocytes predicted cognitive impairment and brain injury.Methods:We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14+ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).Results:The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14+ HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14+ HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.Interpretation:Reservoir burden of HIV DNA in monocyte-enriched (CD14+) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.
UR - http://www.scopus.com/inward/record.url?scp=84881158407&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0070164
DO - 10.1371/journal.pone.0070164
M3 - Article
C2 - 23936155
AN - SCOPUS:84881158407
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 7
M1 - e70164
ER -