Journal
OPEN FORUM INFECTIOUS DISEASES
Volume 6, Issue 5, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/ofid/ofz113
Keywords
cardiovascular disease; CX3CR1 memory cells; people living with HIV; sub clinical CMV
Categories
Funding
- National Institute of Health [R56 HL125028, R24 AI106039, R21 AI127132, AI68636, AI027763]
- International Maternal Pediatric Adolescent AIDS Clinical Trials Network
- National Institute of Allergy and Infectious Diseases, National Institutes of Health [UM1AI068632, UM1AI068616, UM1AI106716]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute of Mental Health
- Flow Cytometry Core at the University of California, San Diego, Center for AIDS Research (National Institute of Health grant) [P30 AI036214]
- VA San Diego Health Care System
- San Diego Veterans Medical Research Foundation
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Background. Persons living with human immunodeficiency virus (HIV) (PLWH) with high cytomegalovirus (CMV)-specific interferon (IFN) gamma response have increased numbers of endothelium homing receptor (CX3CR1)(+)-expressing cells that are associated with cardiovascular disease. The current study was performed to investigate the effect of cellular levels of CMV DNA on these markers. Methods. Eighty paired peripheral blood mononuclear cell samples were collected >= 12 months apart from 40 CMV-seropositive PLWH with suppressed HIV RNA, who started antiretroviral therapy at median of 3-months of infection. The samples were assessed for CMV-specific IFN-gamma response by means of enzyme-linked immunospot assay, and participants were classified as low responders (LRs) or high responders (HRs) based on IFN-gamma production (<= 100 or >100 spot-forming units [SFUs]/10(5) cells). Results. Of the 40 participants, 26 (65%) were HRs and 14 (35%) LRs at baseline, which did not change over time or by CMV levels (median at first/second time points, 383/308 SFUs/10(6) cells for HRs vs 21/41 SFUs/10(6) for LRs). A decrease in IFN-gamma over time was associated with higher CMV DNA levels (P < .01). High CMV response was also associated with increased CD28(+)CD27(-)CD4(+) T cells expressing CX3CR1 (P < .001). Similarly, increased IFN-gamma production was associated with increased CMV-specific CX3CR1(+)CD28(+)CD27(-)CD4(+) and CD8(+) T cells (P < .001). Conclusions. These findings demonstrate that levels of CMV-specific IFN-gamma response in PLWH are stable over time, and that HRs have increased circulating T cells expressing CX3CR1 that may put them at increased risk of cardiovascular disease and other inflammatory diseases.
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