Aging, Inflammation and HIV infection

ArticleinTopics in antiviral medicine 20(3):101-5 · August 2012with10 Reads
Source: PubMed
  • 41.69 · Icahn School of Medicine at Mount Sinai
Prolonged survival in HIV infection is accompanied by an increased frequency of non-HIV-related comorbidities. A number of age-related comorbidities occur earlier in HIV-infected patients than in individuals without HIV infection. This "accelerated aging" appears to be largely related to chronic inflammation, chronic immune activation, and immunosenescence in HIV infection. Levels of markers of inflammation and coagulopathy are elevated in HIV-infected patients, and elevations in markers such as high-sensitivity C-reactive protein, D-dimer, and interleukin 6 (IL-6) have been associated with increased risk for cardiovascular disease, opportunistic conditions, or all-cause mortality. In both HIV infection and aging, immunosenescence is marked by an increased proportion of CD28-, CD57+ memory CD8+ T cells with reduced capacity to produce interleukin 2 (IL-2), increased production of IL-6, resistance to apoptosis, and shortened telomeres. A number of AIDS Clinical Trials Group studies are under way to examine treatment aimed at reducing chronic inflammation and immune activation in HIV infection. This article summarizes a presentation by Judith A. Aberg, MD, at the IAS-USA live continuing medical education course held in New York City in October 2011.
    • "[2][3][4]Hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection and tobacco use, together with long exposure to cART and longstanding HIV replication, may further contribute to the diversification of morbidity and mortality. [5][6][7]Studies from several European countries have reported an important excess mortality in HIV/HCV-coinfected patients. [8,9] However, it is essential to determine the contribution of HCV coinfection to an increased cause-specific mortality in HIV-positive patients. "
    [Show abstract] [Hide abstract] ABSTRACT: We aimed to estimate overall and cause-specific excess mortality of HIV-positive patients compared with the general population, and to assess the effect of risk factors.We included patients aged >19 years, recruited from January 1, 2004 to May 31, 2014 in Cohort of the Spanish Network on HIV/AIDS Research. We used generalized linear models with Poisson error structure to model excess mortality rates.In 10,340 patients, 368 deaths occurred. Excess mortality was 0.82 deaths per 100 person-years for all-cause mortality, 0.11 for liver, 0.08 for non-AIDS-defining malignancies (NADMs), 0.08 for non-AIDS infections, and 0.02 for cardiovascular-related causes. Lower CD4 count and higher HIV viral load, lower education, being male, and over 50 years were predictors of overall excess mortality. Short-term (first year follow-up) overall excess hazard ratio (eHR) for subjects with AIDS at entry was 3.71 (95% confidence interval [CI] 2.66, 5.19) and 1.37 (95% CI 0.87, 2.15) for hepatitis C virus (HCV)-coinfected; medium/long-term eHR for AIDS at entry was 0.90 (95% CI 0.58, 1.39) and 3.83 (95% CI 2.37, 6.19) for HCV coinfection. Liver excess mortality was associated with low CD4 counts and HCV coinfection. Patients aged ≥50 years and HCV-coinfected showed higher NADM excess mortality, and HCV-coinfected patients showed increased non-AIDS infections excess mortality.Overall, liver, NADM, non-AIDS infections, and cardiovascular excesses of mortality associated with being HIV-positive were found, and HCV coinfection and immunodeficiency played significant roles. Differential short and medium/long-term effects of AIDS at entry and HCV coinfection were found for overall excess mortality.
    Full-text · Article · Sep 2016
    • "In addition, OPG would increase the adhesion and migration of inflammatory cells across the endothelium, the activity of metalloproteinases , the inhibition of apoptosis of inflammatory cells, smooth muscle cells and endothelial cells with increased plaque instability4243. The scenario of multiple comorbidities during HIV infection is complicated: virus, ART, immune activation and immunosenescence with pro-inflammatory cytokines play a predominant role4445. Several hypotheses have been advanced to explain the possible relationship between bone and vascular disease as they recognize both risk factors and common pathophysiological mechanisms. "
    [Show abstract] [Hide abstract] ABSTRACT: HIV-infected patients appear to have a significantly greater risk of non-AIDS comorbidities such as osteoporosis and atherosclerosis. Subjects with osteoporosis are at a higher risk of developing cardiovascular disease than those with normal bone mass, therefore a possible relation between these two conditions can be hypothesized. In the setting of HIV infection, several factors might contribute to bone disease and endothelial dysfunction. The aim of our study was to evaluate the relationship between bone and cardiovascular disease and to investigate the role of traditional factors, T-cell phenotype and osteoprotegerin in HIV positive subjects on effective antiretroviral therapy. We included 94 HIV positive subjects on antiretroviral therapy with virological suppression and 41 healthy subjects matched for age and gender as a control group. Carotid-Intima Media Thickness (c-IMT) and bone mineral density (BMD) were performed by ultrasound and DEXA, respectively. CD4+/CD8+ T-cell activation, senescence and osteoprotegerin plasma levels were measured by flow-cytometry and ELISA, respectively. Among HIV positive patients, 56.4% had osteopenia/osteoporosis and 45.7% had pathological c-IMT (>0.9mm). Subjects with pathological c-IMT and BMD exhibited higher CD4+ and CD8+ activated, CD8+ senescent and osteoprotegerin than subjects with normal c-IMT and BMD. HIV positive subjects with osteopenia/osteoporosis had higher c-IMT than subjects with normal BMD, and linear regression analysis showed a negative correlation between BMD and c-IMT. Several factors are implicated in the pathogenesis of non-AIDS comorbidities in HIV positive patients. Osteoprotegerin together with inflammation and immunosenescence in HIV positive patients could affect bone and vascular system and could be considered as a possible common link between these two diseases.
    Full-text · Article · Feb 2016
    • "Our study is novel in its exploration of the relationship CD4 R /CD8 R ratio, age, and NCDs Castilho et al. 903 between age and CD4 þ /CD8 þ ratio as prior studies have largely used case-control designs that have matched on age. Chronic HIV infection has been observed to cause immunologic changes similar to those observed in natural aging, including decreased naive T-lymphocyte populations , increased T-lymphocyte activation, T-lymphocyte replicative senescence, and increased immune activation, among others252627282930. Previous studies have demonstrated that CD4 þ /CD8 þ ratio correlates with a number of these adaptive immune senescence changes in HIV-infected adults on ART [20,21,31]. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: In virologically suppressed HIV-infected adults, non-communicable diseases (NCDs) have been associated with immune senescence and low CD4/CD8 lymphocyte ratio. Age differences in the relationship between CD4/CD8 ratio and NCDs have not been described. Design: Observational cohort study. Methods: We assessed CD4/CD8 ratio and incident NCDs (cardiovascular, cancer, liver, and renal diseases) in HIV-infected adults started on antiretroviral therapy between 1998-2012. Study inclusion began once patients maintained virologic suppression for 12 months (defined as baseline). We examined age and baseline CD4/CD8 ratio and used Cox proportional hazard models to assess baseline CD4/CD8 ratio and NCDs. Results: This study included 2,006 patients. Low baseline CD4/CD8 ratio was associated with older age, male sex, and low CD4 lymphocyte counts. In models adjusting for CD4 lymphocyte count, CD4/CD8 ratio was inversely associated with age (p < 0.01). Among all patients, 182 had incident NCDs, including 46 with coronary artery disease (CAD) events. CD4/CD8 ratio was inversely associated with risk of CAD events (adjusted HR per 0.1 increase in CD4/CD8 ratio = 0.87, 95% CI: 0.76-0.99, p=0.03). This association was driven by those under age 50 years (adjusted HR 0.83 [0.70-0.97], p = 0.02) versus those over age 50 years (adjusted HR = 0.96 [0.79-1.18], p = 0.71). CD4/CD8 ratio was not significantly associated with incident non-cardiac NCDs. Conclusions: Higher CD4/CD8 ratio after one year of HIV virologic suppression was independently predictive of decreased CAD risk, particularly among younger adults. Advanced immune senescence may contribute to CAD events in younger HIV patients on antiretroviral therapy. Copyright (C) 2016 Wolters Kluwer Health, Inc.
    Article · Dec 2015
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