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 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.

Long-term virological effectiveness with darunavir/ritonavir-based salvage therapy in people living with HIV/AIDS from São Paulo, Brazil

2020 ◽  
Vol 31 (10) ◽  
pp. 967-975
Author(s):  
Ariane Melaré Ramos dos Santos ◽  
Amaury Pachione Martins ◽  
Denise Juliato ◽  
Érique José Farias Peixoto de Miranda ◽  
Giselle Ibette Silva Lopez Lopes ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Salvage Therapy ◽  
Sao Paulo ◽  
Poor Adherence ◽  
Cd4 T Cell ◽  
People Living With Hiv ◽  
Living With Hiv ◽  
Cd4 T Cell Count

Even though darunavir/ritonavir (DRV/r) has high potency and a greater genetic barrier, there are few studies on the long-term effectiveness of DRV/r-based salvage therapy in people living with HIV (PLWH) in low and middle-income countries. This retrospective cohort study, from São Paulo, Brazil, included ART-experienced PLWH aged ≥18 years with virological failure (VF) who had started DRV/r plus an optimized background regimen (OBR) between 2008 and 2012. The proportion of patients with viral load (VL) <50 copies/mL, the improved mean CD4+ T cell count and the factors associated with VF during the 144-week follow-up were assessed. The study included 173 patients with the following characteristics [median (interquartile range)]: age 48 (42 -53) years; CD4+ T cell count, 229 (89 -376) cells/mm3; VL, 4.26 (3.70 -4.74) log10; 6 (4 -7) previous regimens; and 100 (38 -156) months of VF. After 144 weeks, 129 (75%) patients had VL< 50 copies/mL and a mean increase in the CD4+ T cell count of 190 cells/mm3. VL>100,000 copies/mL and poor adherence were associated with VF. DRV/r plus an OBR showed high long-term virological suppression and immunological recovery. VL>100,000 copies/mL and poor adherence were associated with VF at 144 weeks.

Mechanisms of immune aging in HIV

2022 ◽  
Vol 136 (1) ◽  
pp. 61-80
Author(s):  
Manon Chauvin ◽  
Delphine Sauce
Keyword(s):  
Immune Activation ◽  
Opportunistic Infections ◽  
People Living With Hiv ◽  
Adaptive Immune ◽  
Hiv Progression ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Living With Hiv ◽  
Hiv 1

Abstract Massive CD4+ T-cell depletion as well as sustained immune activation and inflammation are hallmarks of Human Immunodeficiency Virus (HIV)-1 infection. In recent years, an emerging concept draws an intriguing parallel between HIV-1 infection and aging. Indeed, many of the alterations that affect innate and adaptive immune subsets in HIV-infected individuals are reminiscent of the process of immune aging, characteristic of old age. These changes, of which the presumed cause is the systemic immune activation established in patients, likely participate in the immuno-incompetence described with HIV progression. With the success of antiretroviral therapy (ART), HIV-seropositive patients can now live for many years despite chronic viral infection. However, acquired immunodeficiency syndrome (AIDS)-related opportunistic infections have given way to chronic diseases as the leading cause of death since HIV infection. Therefore, the comparison between HIV-1 infected patients and uninfected elderly individuals goes beyond the sole onset of immunosenescence and extends to the deterioration of several physiological functions related to inflammation and systemic aging. In light of this observation, it is interesting to understand the precise link between immune activation and aging in HIV-1 infection to figure out how to best care for people living with HIV (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.

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.

Lack of virologic suppression is associated with lower HIV-related disclosure stigma in people living with HIV

AIDS Care ◽  
2019 ◽  
Vol 32 (8) ◽  
pp. 1001-1007
Author(s):  
Michelle Matheu ◽  
Thankam Sunil ◽  
Alexandra Castro-Peña ◽  
Camille Elena Spears ◽  
Christopher James Smith ◽  
...  
Keyword(s):  
People Living With Hiv ◽  
Virologic Suppression ◽  
Living With Hiv

scholarly journals Clinical Pharmacology of Hyperammonemia by Sodium Valproate and Carbamazepine in People Living with HIV

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 143-143
Author(s):  
Martin J. Mazzoglio y Nabar ◽  
Santiago Muñoz ◽  
Milagros Muñiz ◽  
Alexis Mejías ◽  
Christian Montivero ◽  
...  
Keyword(s):  
Valproic Acid ◽  
People Living With Hiv ◽  
Preventive Control ◽  
Decompensated Liver Disease ◽  
Viral Loads ◽  
Daily Life Activities ◽  
Psychopharmacological Treatment ◽  
Immunodeficiency Virus ◽  
Cirrhotic Patients ◽  
Living With Hiv

AbstractIntroductionHyperammonaemia (HA) is observed in decompensated liver disease. The picture of hyperammonemic encephalopathy in non-cirrhotic patients was reported mostly associated with valproic acid. There are few reports of hyperammonemia in people living with human immunodeficiency virus (PLHIV) and they are associated with other comorbidities and few with antiretrovirals (HAART), but not as adverse drug reactions associated with psychotropic drugs associated with the virus.ObjectiveReport of cases of PLHIV in HARRT with hyperammonemia, its clinical impact and ammonium levels.Materials and MethodsWe report 67 PLHIV in treatment with HAART, negative viral loads, psychopharmacological treatment with valproic acid (n=45) or carbamazepine (n=22). Exclusion criteria were = HCV, HBV and alcohol consumption disorder (current or recent history) and decompensated liver pathology. We apply scales to evaluate side effects (UKU), subjective adherence (DAI), daily life activities (Barthel Index), liver severity (Child-Pugh Classification) and degrees of hepatic encephalopathy (West Haven Scale). The ethical-legal requirements were met. Results: 26.86% presented hyperammonemia, among which 38.88% was symptomatic. The clinical presentation was heterogeneous with a higher prevalence of gastrointestinal and cognitive alterations; the most severe cases presented alterations of the sensorium and 1 case of convulsions. We recorded a greater symptomatic severity with carbamazepine (average ammonia =104.4 pmol/L), but a higher prevalence of non-symptomatic hyperammonemia with valproic acid (62.3 pmol/L). The time of onset of symptoms was lower with carbamazepine, but the time until its decrease was higher with valproic acid.ConclusionsWe observed a higher prevalence of hyperammonemia and associated symptomatology in PLHIV with HAART medicated with carbamazepine. The significant percentage of this adverse drug reaction suggests a biochemical, perhaps preventive, control.

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