HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Naïve Patients

• Published in: PloS one Vol. 8; no. 7; p. e70164
• Main Authors: Valcour, Victor G., Ananworanich, Jintanat, Agsalda, Melissa, Sailasuta, Napapon, Chalermchai, Thep, Schuetz, Alexandra, Shikuma, Cecilia, Liang, Chin-Yuan, Jirajariyavej, Supunee, Sithinamsuwan, Pasiri, Tipsuk, Somporn, Clifford, David B., Paul, Robert, Fletcher, James L. K., Marovich, Mary A., Slike, Bonnie M., DeGruttola, Victor, Shiramizu, Bruce
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.07.2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Activation; Adult; AIDS; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; Biology; Blood cells; Brain; Brain - metabolism; Brain - pathology; Brain - virology; Brain injury; Brain research; CD14 antigen; CD4 antigen; Cell number; Cerebrospinal fluid; Cognition Disorders - diagnosis; Cognition Disorders - etiology; Cognitive ability; Consent; Copy number; Cytokines; Cytokines - blood; Cytokines - cerebrospinal fluid; Deoxyribonucleic acid; DNA; DNA, Viral - genetics; DNA, Viral - metabolism; Drug therapy; Enrichment; Female; Head injuries; Health risks; HIV; HIV - drug effects; HIV - genetics; HIV - physiology; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - virology; Hospitals; Host-Pathogen Interactions - drug effects; Human immunodeficiency virus; Humans; Immune response; Impairment; Infections; Lipopolysaccharide Receptors - metabolism; Lymphocytes; Lymphocytes T; Magnetic resonance; Magnetic resonance spectroscopy; Male; Markers; Medicine; Monocytes; Monocytes - metabolism; Monocytes - pathology; Monocytes - virology; Multiplex Polymerase Chain Reaction; Multivariate Analysis; N-Acetylaspartate; Neopterin; Neurology; Neuronal-glial interactions; Peripheral blood; Prospective Studies; Public health; Regression Analysis; Reservoirs; Ribonucleic acid; Risk Factors; RNA; ROC Curve; Spectroscopy; Spectrum analysis; Studies; Viruses; San Francisco California; United States > US; Missouri; Hawaii; California; Thailand; Bangkok Thailand
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0070164

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. 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). 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. 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.