101. Early Antiretroviral Therapy Is Associated with Lower HIV DNA Molecular Diversity and Lower Inflammation in Cerebrospinal Fluid but Does Not Prevent the Establishment of Compartmentalized HIV DNA Populations.
- Author
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Oliveira, Michelli F, Chaillon, Antoine, Nakazawa, Masato, Vargas, Milenka, Letendre, Scott L, Strain, Matthew C, Ellis, Ronald J, Morris, Sheldon, Little, Susan J, Smith, Davey M, and Gianella, Sara
- Subjects
Central Nervous System ,Leukocytes ,Mononuclear ,CD4-Positive T-Lymphocytes ,Humans ,HIV-1 ,HIV Infections ,Inflammation ,DNA ,Viral ,RNA ,Viral ,Antiretroviral Therapy ,Highly Active ,Prospective Studies ,Cognition ,Adult ,Male ,Secondary Prevention ,Biomarkers ,Cognitive Dysfunction ,Neurosciences ,Genetics ,Infectious Diseases ,Pediatric AIDS ,HIV/AIDS ,Pediatric ,Mental Health ,Clinical Research ,2.1 Biological and endogenous factors ,Infection ,Adult Antiretroviral Therapy ,Highly Active/*methods Biomarkers/blood/*cerebrospinal fluid CD4-Positive T-Lymphocytes/virology Central Nervous System/*virology Cognition Cognitive Dysfunction/*virology DNA ,Viral/*blood/*cerebrospinal fluid/genetics HIV Infections/*drug therapy/pathology HIV-1/*genetics/physiology Humans Inflammation/drug therapy Leukocytes ,Mononuclear/cytology Male Prospective Studies RNA ,Viral/cerebrospinal fluid Secondary Prevention ,Virology ,Microbiology ,Immunology ,Medical Microbiology - Abstract
Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood and cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants started ART 14 months after EDI ("late ART"). For each participant, neurocognitive functioning was measured by Global Deficit Score (GDS). HIV DNA levels were measured in peripheral blood mononuclear cells (PBMCs) and CSF cell pellets by droplet digital (dd)PCR. Soluble markers of inflammation (sCD163, IL-6, MCP-1, TNF-α) and neuronal damage (neurofilament light [NFL]) were measured in blood and CSF supernatant by immunoassays. HIV-1 partial C2V3 env deep sequencing data (Roche 454) were obtained for 8 paired PBMC and CSF specimens and used for phylogenetic and compartmentalization analysis. Median exposure to ART at the time of sampling was 2.6 years (IQR: 2.2-3.7) and did not differ between groups. We observed that early ART was significantly associated with lower molecular diversity of HIV DNA in CSF (p more...
- Published
- 2017