Year: 2019
Type: article
Study design: Observational Study
Abstract: Background Persons living with human immunodeficiency virus (HIV) (PLWH) with high cytomegalovirus (CMV)–specific interferon (IFN) γ 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-γ response by means of enzyme-linked immunospot assay, and participants were classified as low responders (LRs) or high responders (HRs) based on IFN-γ production (≤100 or >100 spot-forming units [SFUs]/105 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/106 cells for HRs vs 21/41 SFUs/106 for LRs). A decrease in IFN-γ 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-γ 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-γ 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.
Source: Open Forum Infectious Diseases
DOI: 10.1093/ofid/ofz113
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,053
Funders: International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institutes of Health, Center for AIDS Research, University of Washington, University of California, San Diego, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G2027736814, G2839755957, Role of CMV in Heart Disease of HIV-Infected Women and Perinatally Infected Youth, G3262353703, G3342746445, G342295615, AIDS Clinical Trials Group Network, G3789320706, Primary Infection Resource Consortium (PIRC), G4853082081, G495691247, G5057491120, G5202045387, G7103799864, Role of Myeloid Derived Suppressor Cells in Mycobacterium tuberculosis(Mtb)Reactivation in HIV-Mtb co-infected Individuals, Effect of Declining Sex Hormones on HIV persistence in HIV Infected Women on ART, G8259150102, UC San Diego Clinical and Translational Research Institute, G9000015816, G9000078127, G9000124410, SDMC - IMPAACT Leadership Group, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, International Maternal, Adolescent and Pediatric Therapeutics Clinical Trials Network, San Diego Center for AIDS Research (SD CFAR), CURE CTU, UCSF-Bay Area Center for AIDS Research, IMPAACT Leadership Group
OpenAlex ID: W2921706909