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Immune activation and cardiovascular disease in chronic HIV infection.

ABSTRACT: This article describes the potential contribution of immune activation in the pathogenesis of HIV-associated cardiovascular disease (CVD) - a leading cause of morbidity and mortality among HIV-positive persons with access to antiretroviral therapy (ART).We review recent literature that suggests abnormalities in both adaptive and innate immunity contributes to CVD risk among persons with HIV infection. In particular, potentially atherogenic T-cell mechanisms include persistent high-level T-cell activation (and associated proinflammatory mechanisms), as well as the presence of copathogens (e.g., cytomegalovirus) providing an ongoing stimulus for cytotoxic T-cell responses. More recent data have then emphasized the potential impact of monocyte-/macrophage-mediated inflammation and injury within atherosclerotic lesions. The abnormality driving innate immune activation many not fully reverse with antiretroviral therapy, highlighting the need for interventions that target inflammation as a CVD prevention strategy.Premature CVD among persons with HIV infection is due, in part, to persistent abnormalities in immune activation and systemic inflammation despite viral suppression. Prevention strategies for persons with HIV infection include those that target traditional CVD risk factors, as well as newer candidate treatments with potential immunomodulatory benefits.

SUBMITTER: Longenecker CT

PROVIDER: S-EPMC4745252 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Immune activation and cardiovascular disease in chronic HIV infection.

Longenecker Chris T CT Sullivan Claire C Baker Jason V JV

Current opinion in HIV and AIDS 20160301 2

<h4>Purpose of review</h4>This article describes the potential contribution of immune activation in the pathogenesis of HIV-associated cardiovascular disease (CVD) - a leading cause of morbidity and mortality among HIV-positive persons with access to antiretroviral therapy (ART).<h4>Recent findings</h4>We review recent literature that suggests abnormalities in both adaptive and innate immunity contributes to CVD risk among persons with HIV infection. In particular, potentially atherogenic T-cell ...[more]

PMID: 26599166

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Project description:BackgroundConcern about costs and antiretroviral therapy (ART)-associated toxicities led to the consideration of CD4 driven strategies for the management of HIV. That approach was evaluated in the SMART trial that reported an unexpected increase of cardiovascular events after treatment interruption (TI). Our goal was to evaluate fasting metabolic changes associated with interruption of antiretroviral therapy and relate them to changes of immune activation markers and cardiovascular risk.MethodologyACTG 5102 enrolled 47 HIV-1-infected subjects on stable ART, with <200 HIV RNA copies/mL and CD4 cell count >or=500 cells/microL. Subjects were randomly assigned to continue ART for 18 weeks with or without 3 cycles of interleukin-2 (IL-2) (cycle = 4.5 million IU sc BID x 5 days every 8 weeks). After 18 weeks ART was discontinued in all subjects until the CD4 cell count dropped below 350 cells/microL. Glucose and lipid parameters were evaluated every 8 weeks initially and at weeks 2, 4, 8 and every 8 weeks after TI. Immune activation was evaluated by flow-cytometry and soluble TNFR2 levels.Principal findingsBy week 8 of TI, levels of total cholesterol (TC) (median (Q1, Q3) (-0.73 (-1.19, -0.18) mmol/L, p<0.0001), LDL, HDL cholesterol (-0.36(-0.73,-0.03)mmol/L, p = 0.0007 and -0.05(-0.26,0.03), p = 0.0033, respectively) and triglycerides decreased (-0.40 (-0.84, 0.07) mmol/L, p = 0.005). However the TC/HDL ratio remained unchanged (-0.09 (-1.2, 0.5), p = 0.2). Glucose and insulin levels did not change (p = 0.6 and 0.8, respectively). After TI there was marked increase in immune activation (CD8+/HLA-DR+/CD38+ cells, 34% (13, 43), p<0.0001) and soluble TNFR2 (1089 ng/L (-189, 1655), p = 0.0008) coinciding with the rebound of HIV viremia.ConclusionsOur data suggests that interrupting antiretroviral therapy does not reduce cardiovascular disease (CVD) risk, as the improvements in lipid parameters are modest and overshadowed by the decreased HDL levels. Increased immune cell activation and systemic inflammatory responses associated with recrudescent HIV viremia may provide a more cogent explanation for the increased cardiovascular risk associated with treatment interruption and HIV infection.Trial registrationClinicalTrials.gov NCT00015704.

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Immune activation and cardiovascular disease in chronic HIV infection.

Publications

Immune activation and cardiovascular disease in chronic HIV infection.

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