Inflammation and Arterial Injury in Individuals With Human Immunodeficiency Virus Infection.
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ABSTRACT:
SUBMITTER: Stein JH
PROVIDER: S-EPMC5761652 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Publications
Inflammation and Arterial Injury in Individuals With Human Immunodeficiency Virus Infection.
Stein James H JH Hsue Priscilla Y PY
JAMA cardiology 20160701 4
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Project description:ImportanceHuman immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals.ObjectiveTo test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs).Design, setting, and participantsFor this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center. Arterial and LN inflammation were measured using 18F-fluorodeoxyglucose positron emission tomography. Detailed immunophenotyping was performed, along with measurement of viral activity/persistence and of circulating inflammatory biomarkers.Main outcomes and measuresArterial and LN inflammation.ResultsA total of 74 men were studied (45 HIV-infected men with a median age of 53 years [interquartile range, 49-59 years] and 29 uninfected male controls with a median age of 52 years [interquartile range, 46-56 years]). Lymph node inflammation was higher in HIV-infected individuals and correlated with markers of viral disease activity (viral load, CD8+ T cells, and CD4/CD8 ratio) and CD4+ T-cell activation. Uninfected controls had the lowest LN activity (mean [SD] maximum axillary LN standardized uptake value, 1.53 [0.56]), the elite controller and ART-suppressed groups had intermediate levels of LN (mean [SD] maximum axillary LN standardized uptake value, 2.12 [0.87] and 2.32 [1.79], respectively), and the noncontrollers had the highest activity (mean [SD] maximum axillary LN standardized uptake value, 8.82 [3.08]). Arterial inflammation was modestly increased in HIV-infected individuals and was positively correlated with circulating inflammatory biomarkers (high-sensitivity C-reactive protein and IL-6) and activated monocytes (CD14dimCD16+; nonclassical) but not with markers of HIV. While LN and arterial inflammation were increased in HIV, inflammatory activity in these tissues was not related (r = 0.09, P = .56).Conclusions and relevanceWhile LNs and, to a lesser degree, the arterial wall are inflamed in HIV, inflammation in these tissues is not closely linked. Namely, measures of HIV disease activity are strongly associated with LN inflammation but not with arterial inflammation. These data suggest that LN and arterial inflammation do not share underlying pathways of immune activation and also that therapeutic interventions that reduce viral disease activity may not predictably reduce arterial inflammation in HIV or its downstream consequence (ie, cardiovascular disease).
| S-EPMC5310978 | biostudies-literature
Project description:ImportanceIndividuals with human immunodeficiency virus (HIV) infection receiving combined antiretroviral therapy (ART) have an increased risk of myocardial infarction. Effects of ART on arterial inflammation among treatment-naive individuals with HIV are unknown.ObjectiveTo determine the effects of newly initiated ART on arterial inflammation and other immune/inflammatory indices in ART-naive patients with HIV infection.Design, setting, participantsTwelve treatment-naive HIV-infected individuals underwent fludeoxyglucose F 18 ([18F]-FDG) positron emission tomographic scanning for assessment of arterial inflammation, coronary computed tomographic angiography for assessment of subclinical atherosclerosis, and systemic immune and metabolic phenotyping before and 6 months after the initiation of therapy with elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (combined ART). Systemic immune and metabolic factors were also assessed in 12 prospectively recruited individuals without HIV serving as controls. The study began July 24, 2012, and was completed May 7, 2015.InterventionsCombined ART in the HIV-infected cohort.Main outcomes and measuresThe primary outcome was change in aortic target-background ratio (TBR) on [18F]-FDG-PET with combined ART in the HIV-infected group.ResultsFor the 12 participants with HIV infection (mean (SD) age, 35 [11] years), combined ART suppressed viral load (mean [SD] log viral load, from 4.3 [0.6] to 1.3 [0] copies/mL; P < .001), increased the CD4+ T-cell count (median [IQR], from 461 [332-663] to 687 [533-882] cells/mm3; P < .001), and markedly reduced percentages of circulating activated CD4+ T cells (human leukocyte antigen-D related [HLA-DR]+CD38+CD4+) (from 3.7 [1.8-5.0] to 1.3 [0.3-2.0]; P = .008) and CD8+ T cells (HLA-DR+CD38+CD8+) (from 18.3 [8.1-27.0] to 4.0 [1.5-7.8]; P = .008), increased the percentage of circulating classical CD14+CD16- monocytes (from 85.8 [83.7-90.8] to 91.8 [87.5-93.2]; P = .04), and reduced levels of CXCL10 (mean [SD] log CXCL10, from 2.4 [0.4] to 2.2 [0.4] pg/mL; P = .03). With combined ART, uptake of [18F]-FDG in the axillary lymph nodes, as measured by TBR, decreased from a median (IQR) of 3.7 (1.3-7.0) at baseline to 1.4 (0.9-1.9; P = .01) at study end. In contrast, no significant decrease was seen in aortic TBR in response to combined ART (mean [SD], 1.9 [0.2]; median [IQR], 2.0 [1.8-2.1] at baseline to 2.2 [0.4]; 2.1 [1.9-2.6], respectively, at study end; P = .04 by 2-way test, P = .98 for test of decrease by 1-way test). Changes in aortic TBR during combined ART were significantly associated with changes in lipoprotein-associated phospholipase A2 (n = 10; r = 0.67; P = .03). Coronary plaque increased among 3 participants with HIV infection with baseline plaque and developed de novo in 1 participant during combined ART.Conclusions and relevanceNewly initiated combined ART in treatment-naive individuals with HIV infection had discordant effects to restore immune function without reducing arterial inflammation. Complementary strategies to reduce arterial inflammation among ART-treated HIV-infected individuals may be needed.
| S-EPMC5944348 | biostudies-literature
Project description:BackgroundThis study was conducted to explore the associations between serum albumin and markers of inflammation and cardiovascular disease in treated human immunodeficiency virus (HIV)-infected adults.MethodsWe conducted a nested study within in the SATURN-HIV trial in which 147 HIV+ adults on stable antiretroviral therapy were (1) virally suppressed, (2) had a low-density lipoprotein (LDL)-cholesterol level <130 mg/dL, and (3) were randomized to 10 mg daily rosuvastatin or placebo. Measures of serum albumin, carotid intima media thickness ([cIMT] surrogate marker of atherosclerosis), inflammation, T cells, monocyte activation, and gut integrity were assessed at baseline, 48 and 96 weeks later. Spearman correlations and linear mixed-effect models were used to assess associations with serum albumin.ResultsMean age was 45 years, 80% of participants were male, and 69% were African American. Mean serum albumin was similar between the groups at all time points (4.01-4.09 g/dL in statin arm vs 4.02-4.11 g/dL in placebo arm; P = .08-0.35). Lower baseline serum albumin significantly predicted larger changes in cIMT, interleukin 6, D-dimer, tumor necrosis factor α receptor 1, fibrinogen, and high-sensitivity C-reactive protein (P ≤ .03) over 96 weeks independently of statin therapy. After adjusting for age, gender, smoking, body mass index, creatinine clearance, and LDL cholesterol, every 1 g/dL decrease in serum albumin at baseline remained associated with a 0.05-mm increase in cIMT over 96 weeks (P = .05).ConclusionsLower serum albumin in controlled HIV is associated with higher markers of chronic inflammation and hypercoagulation, which could explain the prior observation that serum albumin predicts nonacquired immune deficiency syndrome events in HIV. Serum albumin may predict progression of carotid atherosclerosis independent of traditional risk factors.
| S-EPMC6262118 | biostudies-literature
Project description:Human immunodeficiency virus (HIV) infection is associated with increased systemic microbial translocation, neuroinflammation, and occasionally, neuronal injury. Whether systemic lipopolysaccharide (LPS) penetrates into the brain and contributes to neuroinflammation remain unknown in HIV. Here, we measured plasma and cerebrospinal fluid (CSF) LPS levels along with biomarkers of neuroinflammation (white blood cell counts and 40 soluble markers) and neurofilament light chain (NfL). Notably, CSF LPS was undetectable in all samples, including 3 HIV-infected individuals with dementia. Increased plasma LPS, neuroinflammation, and blood-brain barrier (BBB) dysfunction were found in untreated HIV-infected individuals, but not in healthy or treated HIV-infected individuals. Plasma LPS levels were directly correlated with various markers of inflammation in both plasma and CSF, as well as with degree of BBB permeability but not with CSF NfL in HIV-infected subjects. These results suggest that the magnitude of microbial translocation associates with neuroinflammation and BBB permeability in HIV without direct penetration into the central nervous system.
| S-EPMC8136977 | biostudies-literature
Project description:Previous studies have noted that persons living with human immunodeficiency virus (HIV) experience persistent lung dysfunction after an episode of community-acquired pneumonia (CAP), although the underlying mechanisms remain unclear. We hypothesized that inflammation during pneumonia triggers increased tissue damage and accelerated pulmonary fibrosis, resulting in a gradual loss of lung function. We carried out a prospective cohort study of people diagnosed with CAP and/or HIV between 2016 and 2018 in three clinical institutions in Medellín, Colombia. Clinical data, blood samples, and pulmonary function tests (PFTs) were collected at baseline. Forty-one patients were included, divided into two groups: HIV and CAP (n = 17) and HIV alone (n = 24). We compared the concentrations of 17 molecules and PFT values between the groups. Patients with HIV and pneumonia presented elevated levels of cytokines and chemokines (IL-6, IL-8, IL-18, IL-1RA, IL-10, IP-10, MCP-1, and MIP-1β) compared to those with only HIV. A marked pulmonary dysfunction was evidenced by significant reductions in FEF25, FEF25-75, and FEV1. The correlation between these immune mediators and lung function parameters supports the connection between pneumonia-associated inflammation and end organ lung dysfunction. A low CD4 cell count (<200 cells/μL) predicted inflammation and lung dysfunction. These results underscore the need for targeted clinical approaches to mitigate the adverse impacts of CAP on lung function in this population.
| S-EPMC10820350 | biostudies-literature
Project description:BackgroundPatients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status.MethodsWe conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups.ResultsAmong HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons.ConclusionsRegardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.
| S-EPMC5850026 | biostudies-literature
Project description:CD4(-) epithelial cells covering mucosal surfaces serve as the primary barrier to prevent human immunodeficiency virus type 1 (HIV-1) infection. We used HIV-1 vectors carrying the enhanced green fluorescent protein gene as a reporter gene to demonstrate that HIV-1 can infect some CD4(-) human epithelial cell lines with low but significant efficiencies. Importantly, HIV-1 infection of these cell lines is independent of HIV-1 envelope proteins. The Env-independent infection of CD4(-) cells by HIV-1 suggests an alternative pathway for HIV-1 transmission. Even on virions bearing Env, a neutralizing antibody directed against gp120 is incapable of neutralizing the infection of these cells, thus raising potential implications for HIV-1 vaccine development.
| S-EPMC113179 | biostudies-literature
Project description:BackgroundMycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection.MethodsPlasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication.ResultsWe observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells.ConclusionsPre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.
| S-EPMC7529013 | biostudies-literature
Project description:The incidence of anal cancer is increasing in the general population and especially in high-risk groups. A total of 90% of anal cancers are caused by human papilloma virus (HPV) infection of the anal canal. Similar to cervical cancer, anal cancer progresses through a predictable series of premalignant stages before resulting in invasive cancer; this process begins with persistent HPV infection. The HPV vaccine represents a promising strategy to combat the increasing incidence of anal cancer. Human Immunodeficiency Virus (HIV) predisposes people to persistent HPV infection, dysplasia, and subsequent anal cancer. Patients infected with HIV should be targeted for vaccination against HPV. There are difficulties in targeting this population, the most notable being that the optimal age for vaccination is prior to identification with any high-risk groups. Universal vaccination against HPV represents the best strategy to achieve maximum protection against anal cancer in high-risk groups.
| S-EPMC3967665 | biostudies-literature
Project description:Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and, to a lesser extent, through blood transfusion and blood products. Recently, there has been an increase in HCV infections among men who have sex with men. In the context of effective antiretroviral treatment, liver-related deaths are now more common than Acquired Immune Deficiency Syndrome-related deaths among HIV-HCV coinfected individuals. Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20% of chronically infected individuals. HCV treatment has rapidly changed with the development of new direct-acting antiviral agents; therefore, cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle. In this review, we focus on the epidemiology, diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.
| S-EPMC4161799 | biostudies-literature