Systemic inflammation and risk of age-associated diseases in people living with HIV on long term suppressive antiretroviral therapy

2018 ◽  
Author(s):  
Hemalatha Babu ◽  
Anoop T Ambikan ◽  
Erin E Gabriel ◽  
Sara Svensson Akusjärvi ◽  
Alangudi Natarajan Palaniapan ◽  
...  
Keyword(s):  
Linear Regression ◽  
Telomere Length ◽  
Systemic Inflammation ◽  
Immune Activation ◽  
People Living With Hiv ◽  
Associated Diseases ◽  
Markers Of Inflammation ◽  
Age Related ◽  
Living With Hiv

AbstractThe ART program in low- and middle-income countries (LMIC) like India, has a public health approach with the standardized regimen for all people living with HIV (PLHIV). Based on the evidence from high-income countries (HIC), the successful implication and scale-up of ART in India, the risk of an enhanced and accentuated onset of premature-aging or age-related diseases could be observed in PLHIV. However, very limited data is available on residual inflammation and immune activation in the populations who are on first-generation anti-HIV drugs like zidovudine and lamivudine that had more toxic side effects. Therefore, the aim of the present study was to evaluate the levels of systemic inflammation and understand the risk of age-associated diseases in PLHIV on long-term suppressive ART using a large number of biomarkers of the inflammation and immune activation. Blood samples were obtained from therapy naïve PLHIV (Pre-ART, n=43), PLHIV on ART for >5 years (ART, n=53), and HIV-negative healthy controls (HIVNC, n=41). Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, and telomere length. Several statistical tests were performed to compare the groups under study. Multivariate linear regression was used to investigate the associations. Despite a median duration of eight years of successful ART, sCD14 (p<0.001) and sCD163 (p=0.04) levels continued to be significantly elevated in ART group as compared to HIVNC. Eleven inflammatory markers, including 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL and TRANCE, were found to be significantly different (p<0.05) between the groups. Many of these markers are associated with age-related co-morbidities including cardiovascular disease, neurocognitive decline and some of these markers are being reported for the first time in the context of HIV-induced inflammation. Linear regression analysis showed a significant negative association between HIV-1-positivity and telomere length (p<0.0001). In ART-group CXCL1 (p=0.048) and TGF-α (p=0.026) have a significant association with increased telomere length and IL-10RA was significantly associated with decreased telomere length (p=0.042). This observation warrants further mechanistic studies to generate evidence to highlight the need for enhanced treatment monitoring and special interventions in HIV-infected individuals.

scholarly journals Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 200 ◽  
Author(s):  
Sonia Zicari ◽  
Libera Sessa ◽  
Nicola Cotugno ◽  
Alessandra Ruggiero ◽  
Elena Morrocchi ◽  
...  
Keyword(s):  
Immune Activation ◽  
People Living With Hiv ◽  
Residual Viremia ◽  
Immune Exhaustion ◽  
Full Control ◽  
Increased Risk ◽  
Persistent Antigen ◽  
Gut Mucosa ◽  
Living With Hiv

Despite effective antiretroviral therapy (ART), people living with HIV (PLWH) still present persistent chronic immune activation and inflammation. This condition is the result of several factors including thymic dysfunction, persistent antigen stimulation due to low residual viremia, microbial translocation and dysbiosis, caused by the disruption of the gut mucosa, co-infections, and cumulative ART toxicity. All of these factors can create a vicious cycle that does not allow the full control of immune activation and inflammation, leading to an increased risk of developing non-AIDS co-morbidities such as metabolic syndrome and cardiovascular diseases. This review aims to provide an overview of the most recent data about HIV-associated inflammation and chronic immune exhaustion in PLWH under effective ART. Furthermore, we discuss new therapy approaches that are currently being tested to reduce the risk of developing inflammation, ART toxicity, and non-AIDS co-morbidities.

scholarly journals Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1266
Author(s):  
Léna Royston ◽  
Stéphane Isnard ◽  
John Lin ◽  
Jean-Pierre Routy
Keyword(s):  
Immune Activation ◽  
Rapid Development ◽  
People Living With Hiv ◽  
Virologic Suppression ◽  
Vaccine Response ◽  
Comprehensive Overview ◽  
Immunodeficiency Virus ◽  
Living With Hiv ◽  
Cd4 T Cell Count

In stark contrast to the rapid development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective human immunodeficiency virus (HIV) vaccine is still lacking. Furthermore, despite virologic suppression and CD4 T-cell count normalization with antiretroviral therapy (ART), people living with HIV (PLWH) still exhibit increased morbidity and mortality compared to the general population. Such differences in health outcomes are related to higher risk behaviors, but also to HIV-related immune activation and viral coinfections. Among these coinfections, cytomegalovirus (CMV) latent infection is a well-known inducer of long-term immune dysregulation. Cytomegalovirus contributes to the persistent immune activation in PLWH receiving ART by directly skewing immune response toward itself, and by increasing immune activation through modification of the gut microbiota and microbial translocation. In addition, through induction of immunosenescence, CMV has been associated with a decreased response to infections and vaccines. This review provides a comprehensive overview of the influence of CMV on the immune system, the mechanisms underlying a reduced response to vaccines, and discuss new therapeutic advances targeting CMV that could be used to improve vaccine response in PLWH.

scholarly journals The Dietary Inflammatory Index Is Not Associated With Gut Permeability or Biomarkers of Systemic Inflammation in HIV Immunologic Non-responders

2021 ◽  
Vol 8 ◽  
Author(s):  
Fat Malazogu ◽  
Rodney K. Rousseau ◽  
Nitin Shivappa ◽  
Sanja Huibner ◽  
Sharon L. Walmsley ◽  
...  
Keyword(s):  
T Cell ◽  
Systemic Inflammation ◽  
Immune Activation ◽  
Cd4 T Cell ◽  
Gut Permeability ◽  
Inflammatory Index ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Persons Living With Hiv ◽  
Living With Hiv

Immunologic non-responders (INRs) are a subset of individuals living with HIV who have suboptimal blood CD4+ T cell recovery despite effective antiretroviral therapy (ART). They are at an increased risk of serious non-AIDS co-morbidities and death, and demonstrate enhanced systemic immune activation. In other populations diet has been correlated with markers of systemic inflammation through the Diet Inflammatory Index (DII), but this association has not been studied in persons living with HIV (PLWH). Blood was collected from 28 INR PLWH with a blood CD4+ T cell count &lt;350/μL despite ≥2 years of effective ART. Participants completed a Canadian Diet History Questionnaire, and their responses were used to calculate the DII. Plasma inflammatory markers (IFNγ, TNF, IL-6, sVCAM, D-dimer, sCD14 and CRP) were assayed by ELISA, cellular immune activation (HLA-DR and CD38 on CD4+ and CD8+ T cells) was quantified using flow cytometry, and small bowel permeability assessed by calculation of the urine LacMan ratio after drinking a mix of lactulose and mannitol. Participants were a median age of 57 years, had been on effective ART for 15 years, and the median DII was −1.91 (range of −3.78 to +2.23). No correlation was observed between DII and plasma markers of inflammation, levels of T cell activation, gut permeability, or the biomarker of bacterial translocation sCD14. Self-reported alcohol intake, a potential confounder of the relationship between diet and inflammatory biomarkers, was also not associated with systemic inflammation or gut permeability. Our findings suggest that other mechanisms, rather than diet, are likely to be the major driver of systemic inflammation in INR individuals.

scholarly journals Adjunct Therapy for CD4+ T-Cell Recovery, Inflammation and Immune Activation in People Living With HIV: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Zhang ◽  
Taiyi Jiang ◽  
Aixin Li ◽  
Zhen Li ◽  
Jianhua Hou ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cell ◽  
Cell Count ◽  
Immune Activation ◽  
Meta Analysis ◽  
People Living With Hiv ◽  
Cell Recovery ◽  
Cell Counts ◽  
Living With Hiv

Background: HIV infection results in immune homeostasis perturbations, which is characterized by CD4+ T-cell depletion, immune activation, and inflammation. Effective antiretroviral therapy (ART) does not fully restore immunologic and clinical health in people living with HIV (PLWH). Various drugs have been used to improve their immune status and CD4+ T-cell counts, but no measures have been tested effective. Here we conduct a systematic review and meta-analysis of existing clinical studies on improving CD4+ T-cell count while decreasing inflammation and immune activation.Methods: We retrieved possible relevant publications from a total of five electronic databases and selected eligible studies, which dealt with outcomes of medical therapy for CD4+ T-cell count recovery, inflammation, and immune activation with or without ART. We paid particular attention to immunologic non-responders with a favorable treatment regimen.Results: Thirty-three articles were included in the systematic review and meta-analysis. However, there were no safe and effective medications specific for improving CD4+ T-cell reconstitution. The immunological benefits or adverse events mainly depend on the safety, dosage, and duration of the candidate medication use, as well as whether it is combined with ART.Conclusion: Under the “safe, combined, adequate and long (SCAL)” principles, alternative approaches are needed to accelerate the recovery of CD4+ T-cells, and to prevent adverse long-term outcomes in PLWH with standard ART treatment.

scholarly journals Antiretroviral Therapy Dampens Mucosal CD4+ T Lamina Propria Lymphocytes Immune Activation in Long-Term Treated People Living with HIV-1

2021 ◽  
Vol 9 (8) ◽  
pp. 1624
Author(s):  
Alessandro Lazzaro ◽  
Giuseppe Pietro Innocenti ◽  
Letizia Santinelli ◽  
Claudia Pinacchio ◽  
Gabriella De Girolamo ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Lamina Propria ◽  
Immune Activation ◽  
Cd4 T Cells ◽  
People Living With Hiv ◽  
Living With Hiv ◽  
Lamina Propria Lymphocytes ◽  
Hiv 1

HIV infection is characterized by a severe deterioration of an immune cell-mediated response due to a progressive loss of CD4+ T cells from gastrointestinal tract, with a preferential loss of IL-17 producing Th cells (Th17), a specific CD4+ T cells subset specialized in maintaining mucosal integrity and antimicrobial inflammatory responses. To address the effectiveness of antiretroviral therapy (ART) in reducing chronic immunological dysfunction and immune activation of intestinal mucosa, we conducted a cross-sectional observational study comparing total IFN-γ-expressing (Th1) and IL-17-expressing (Th17) frequencies of CD4+ T lamina propria lymphocytes (LPLs) and their immune activation status between 11 male ART-naïve and 11 male long-term ART-treated people living with HIV-1 (PLWH) who underwent colonoscopy and retrograde ileoscopy for biopsies collection. Flow cytometry for surface and intracellular staining was performed. Long-term ART-treated PLWH showed lower levels of CD38+ and/or HLA-DR+ LPLs compared to ART-naïve PLWH. Frequencies of Th1 and Th17 LPLs did not differ between the two groups. Despite ART failing to restore the Th1 and Th17 levels within the gut mucosa, it is effective in increasing overall CD4+ T LPLs frequencies and reducing mucosal immune activation.

scholarly journals Stigma mastery in people living with HIV: gender similarities and theory

2021 ◽  
Author(s):  
Charles Patrick Namisi ◽  
John C. Munene ◽  
Rhoda K. Wanyenze ◽  
Anne R. Katahoire ◽  
Rosalinda M. Parkes-Ratanshi ◽  
...  
Keyword(s):  
Older Women ◽  
Social Exclusion ◽  
Theoretical Framework ◽  
People Living With Hiv ◽  
Negative Effects ◽  
Hiv Diagnosis ◽  
Cross Sectional ◽  
Age Related ◽  
Related Stigma ◽  
Living With Hiv

Abstract Aims This study aimed to determine the prevalence of, factors associated with, and to build a theoretical framework for understanding Internalsed HIV-related Stigma Mastery (IHSM). Methods A cross-sectional study nested within a 2014 Stigma Reduction Cohort in Uganda was used. The PLHIV Stigma Index version 2008, was used to collect data from a random sample of 666 people living with HIV (PLHIV) stratified by gender and age. SPSS24 with Amos27 softwares were used to build a sequential-mediation model. Results The majority of participants were women (65%), aged ≥ 40 years (57%). Overall, IHSM was 45.5% among PLHIV, that increased with age. Specifically, higher IHSM correlated with men and older women “masculine identities” self-disclosure of HIV-diagnosis to family, sharing experiences with peers. However, lower IHSM correlated with feminine gender, the experience of social exclusion stress, fear of future rejection, and fear of social intimacy. Thus, IHSM social exclusion with its negative effects and age-related cognition are integrated into a multidimensional IHSM theoretical framework with a good model-to-data fit. Conclusion Internalised HIV-related Stigma Mastery is common among men and older women. Specificially, “masculine identities” self-disclose their own HIV-positive diagnosis to their family, share experiences with peers to create good relationships for actualising or empowerment in stigma mastery. However, social exclusion exacerbates series of negative effects that finally undermine stigma mastery by young feminine identities. Thus, stigma mastery is best explained by an integrated empowerment framework, that has implications for future practice, policy, and stigma-related research that we discuss.

scholarly journals DNA methylation is associated with airflow obstruction in patients living with HIV

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215866
Author(s):  
Ana I Hernandez Cordero ◽  
Chen Xi Yang ◽  
Maen Obeidat ◽  
Julia Yang ◽  
Julie MacIsaac ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lung Function ◽  
Viral Infections ◽  
Airflow Obstruction ◽  
Normal Lung ◽  
People Living With Hiv ◽  
Global Methylation ◽  
Age Related ◽  
Impaired Lung Function ◽  
Living With Hiv

IntroductionPeople living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH.MethodsUsing blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV1, FEV1/FVC ratio and FEV1 decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing.ResultsAirflow obstruction as defined by a FEV1/FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV1/FVC<lower limit of normal. These DMPs were enriched for biological pathways associated with chronic viral infections. The airflow obstruction group was globally hypomethylated compared with those without airflow obstruction. 103 and 7112 DMPs were associated with FEV1 and FEV1/FVC, respectively. No positions were associated with FEV1 decline.ConclusionA large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.

scholarly journals Substance use, Unlike Dolutegravir, is Associated with Mood Symptoms in People Living with HIV

2021 ◽  
Author(s):  
Lisa Van de Wijer ◽  
Wouter van der Heijden ◽  
Mike van Verseveld ◽  
Mihai Netea ◽  
Quirijn de Mast ◽  
...  
Keyword(s):  
Substance Use ◽  
Term Treatment ◽  
Assessment Tools ◽  
Self Report ◽  
People Living With Hiv ◽  
Antiretroviral Drug ◽  
Long Term Treatment ◽  
Living With Hiv ◽  
Neuropsychiatric Side Effects

AbstractContradictory data have been reported concerning neuropsychiatric side effects of the first-line antiretroviral drug dolutegravir, which may be partly due to lack of control groups or psychiatric assessment tools. Using validated self-report questionnaires, we compared mood and anxiety (DASS-42), impulsivity (BIS-11), and substance use (MATE-Q) between dolutegravir-treated and dolutegravir-naive people living with HIV (PLHIV). We analyzed 194, mostly male, PLHIV on long-term treatment of whom 82/194 (42.3%) used dolutegravir for a median (IQR) of 280 (258) days. Overall, 51/194 (26.3%) participants reported DASS-42 scores above the normal cut-off, 27/194 (13.5%) were classified as highly impulsive, and 58/194 (29.9%) regularly used recreational drugs. Regular substance use was positively associated with depression (p = 0.012) and stress scores (p = 0.045). We observed no differences between dolutegravir-treated and dolutegravir-naive PLHIV. Our data show that depressed and anxious moods and impulsivity are common in PLHIV and associate with substance use and not with dolutegravir use.

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