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 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.

HIV and Bone Health

2017 ◽  
Author(s):  
Linda A. Battalora ◽  
Benjamin Young
Keyword(s):  
Bone Disease ◽  
Assessment Tool ◽  
People Living With Hiv ◽  
Neurocognitive Deficits ◽  
Term Survival ◽  
Metabolic Bone ◽  
Increased Risk ◽  
Fracture Risk Assessment Tool ◽  
Living With Hiv

With improved long-term survival among populations of people living with HIV, it has been suggested that HIV/AIDS may hasten the aging process. There is increasing evidence that cardiovascular, renal, and bone disease and neurocognitive deficits may be more common among long-term survivors of HIV infection. Findings from cohort and prospective randomized studies suggest that people living with HIV are at increased risk of metabolic bone disease and related fractures. There are limited HIV-specific evidence-based recommendations regarding screening for bone disease. Several organizations recommend using dual-energy X-ray absorptiometry and/or the Fracture Risk Assessment Tool for screening of HIV-infected persons at risk of fractures.

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 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.

Kept clinical visits, as scheduled in the first 6 months of antiretroviral treatment, determine long-term treatment outcomes in people living with HIV: a large retrospective cohort study in China

Sexual Health ◽  
2018 ◽  
Vol 15 (1) ◽  
pp. 20
Author(s):  
Shu Su ◽  
Limin Mao ◽  
Jianmei He ◽  
Xiuqing Wei ◽  
Jun Jing ◽  
...  
Keyword(s):  
Term Treatment ◽  
Clinical Monitoring ◽  
Observational Research ◽  
People Living With Hiv ◽  
Research Database ◽  
Increased Risk ◽  
Long Term Treatment ◽  
Living With Hiv ◽  
Related Mortality

Background Routine HIV clinical monitoring is vital for people living with HIV (PLHIV) after treatment initiation. The relationship between clinical visits during the first 6 months after initial antiretroviral therapy (ART) and long-term, HIV-related mortality and service retention was investigated. Methods: A retrospective ART observational research database was established based on de-identified data extracted from 6959 records of adult HIV-positive registrants held by Hunan CDC (Center for Disease Control and Prevention) between 2003 and 2013. Results: During the first 6 months of initiation into ART, 2364 (34.0%) of PLHIV had completed four scheduled visits, meeting the Chinese ART clinical monitoring standards. From 6 months onwards (up to 36 months), this group had the lowest HIV-related mortality (4.4%) compared with those who had more or less than four kept visits in the first 6 months [one visit only: adjusted hazards ratio (AHR) = 3.15, 95% CI 2.24–3.88; two visits: AHR = 2.24, 95% CI 1.80–3.01; three visits: AHR = 1.86, 95% CI 1.69–2.05; and >4 visits: AHR = 1.37, 95% CI 1.11–1.72]. Those with less than three kept visits were also at increased risk of cohort loss to follow up (ART discontinuation, prolonged service disengagement or death). A myriad of personal, clinical and social factors are identified to be associated with increased HIV-related mortality and clinical retention. Conclusions: Enabling PLHIV to complete four scheduled clinical visits during the first 6 months of ART initiation, as recommended by the Chinese CDC, is critical.

Living with HIV in the Time of COVID-19

2020 ◽  
Vol 10 (1) ◽  
pp. 5-7
Author(s):  
Muhammad Naveed Noor
Keyword(s):  
Medical Care ◽  
Developing Country ◽  
People Living With Hiv ◽  
Evidence Based ◽  
Comorbid Conditions ◽  
Increased Risk ◽  
Associated Conditions ◽  
Living With Hiv

This commentary foregrounds the need to examine how the coronavirus disease 2019 (COVID-19) pandemic and associated conditions may be affecting the lives of people living with HIV (PLWH) in a developing country context like Pakistan. It raises some important questions on medical care and updated information regarding PLWH in the time of COVID-19. Since PLWH are at an increased risk of developing comorbid conditions – something that makes them more vulnerable to COVID-19 – it is critical that timely research and evidence-based actions are undertaken to protect their health.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India – A Prospective Cohort Study

2020 ◽  
Vol 18 ◽  
Author(s):  
Rajendra Bhati ◽  
Pramendra Sirohi ◽  
Bharat Sejoo ◽  
Deepak Kumar ◽  
Gopal K Bohra ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Morbidity And Mortality ◽  
People Living With Hiv ◽  
Cryptococcal Antigen ◽  
North West ◽  
Cryptococcal Disease ◽  
Increased Risk ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and pre-emptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. Method and material: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. Results: A total of 116 patients were analysed. Asymptomatic cryptococcal antigenemia was detected in 5.17% patients and it correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Conclusion: Serum cryptococcal positivity is correlated with increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

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