scholarly journals A Subset of Extreme Human Immunodeficiency Virus (HIV) Controllers Is Characterized by a Small HIV Blood Reservoir and a Weak T-Cell Activation Level

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Etienne Canouï ◽  
Camille Lécuroux ◽  
Véronique Avettand-Fenoël ◽  
Marine Gousset ◽  
Christine Rouzioux ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
T Cell ◽  
Cell Count ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
Cd4 T Cell Count

Abstract Background Human immunodeficiency virus controllers (HICs) form a heterogeneous group of patients with regard to formal definitions, immunologic characteristics, and changes over time in viral load. Patients and Methods The HICs with undetectable viral load ([uHICs] ie, for whom a viral load had never been detected with routine assays; n = 52) were compared with 178 HICs with blips during the follow up (bHICs). Clinical characteristics, ultrasensitive HIV-ribonucleic acid (RNA) and HIV-deoxyribonucleic acid (DNA) loads, HIV1-Western blot profiles, and immune parameters were analyzed. Results Relative to bHICs, uHICs had significantly lower ultrasensitive plasma HIV-RNA loads (P < .0001) and HIV-DNA levels in peripheral blood mononuclear cells (P = .0004), higher CD4+ T-cell count (P = .04) at enrollment, and lower T-cell activation levels. Between diagnosis and inclusion in the cohort, the CD4+ T-cell count had not changed in uHICs but had significantly decreased in bHICs. Twenty-one percent of the uHICs lacked specific anti-HIV immunoglobulin G antibodies, and these individuals also had very low levels of HIV-DNA. Half of the uHICs had a protective human leukocyte antigen (HLA) allele (-B57/58/B27), a weak CD8+ T-cell response, and very small HIV-DNA reservoir. Conclusions We suggest that an interesting HIC phenotype combines protective HLA alleles, low level of HIV blood reservoirs, and reduced immune activation. Prospective studies aimed at evaluating the benefit of combined antiretroviral therapy in HICs might take into account the identification of uHICs and bHICs.

scholarly journals Anti-cytomegalovirus Immunoglobulin G Is Linked to CD4 T-cell Count Decay in Human Immunodeficiency Virus (HIV) Elite Controllers

2020 ◽  
Author(s):  
Stephane Isnard ◽  
Rayoun Ramendra ◽  
John Lin ◽  
Sanket Kant ◽  
Brandon Fombuena ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Cell Count ◽  
Immunoglobulin G ◽  
Human Leukocyte ◽  
Cd4 T Cell ◽  
Elite Controllers ◽  
Leukocyte Antigen ◽  
Immunodeficiency Virus ◽  
Cd4 T Cell Count

Abstract Elite controllers (ECs) are people living with human immunodeficiency virus (HIV) who spontaneously control viral replication without antiretroviral therapy. We observed that elevated anti-cytomegalovirus (CMV) immunoglobulin G (IgG) levels correlated with annual CD4 T-cell count decay in ECs independently of age, sex, and human leukocyte antigen (HLA) type. Elevated anti-CMV titers may favor disease progression in ECs.

scholarly journals Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Ashwin Balagopal ◽  
Nikhil Gupte ◽  
Rupak Shivakoti ◽  
Andrea L. Cox ◽  
Wei-Teng Yang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Interferon Γ ◽  
Cd4 T Cell ◽  
Clinical Failure ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Cd4 T Cell Count

Abstract Background.  We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods.  We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results.  Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27–7.20), sCD14 (IRR, 2.17; 95% CI, 1.02–4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01–0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions.  Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function.

scholarly journals Neutrophils promote T-cell activation through the regulated release of CD44-bound Galectin-9 from the cell surface during HIV infection

PLoS Biology ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. e3001387
Author(s):  
Garett Dunsmore ◽  
Eliana Perez Rosero ◽  
Shima Shahbaz ◽  
Deanna M. Santer ◽  
Juan Jovel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Hiv Infection ◽  
Cell Count ◽  
T Cell Activation ◽  
Cell Activation ◽  
Infected Individual ◽  
Cd4 T Cell ◽  
Cd4 T Cell Count

The interaction of neutrophils with T cells has been the subject of debate and controversies. Previous studies have suggested that neutrophils may suppress or activate T cells. Despite these studies, the interaction between neutrophils and T cells has remained a largely unexplored field. Here, based on our RNA sequencing (RNA-seq) analysis, we found that neutrophils have differential transcriptional and functional profiling depending on the CD4 T-cell count of the HIV-infected individual. In particular, we identified that neutrophils in healthy individuals express surface Galectin-9 (Gal-9), which is down-regulated upon activation, and is consistently down-regulated in HIV-infected individuals. However, down-regulation of Gal-9 was associated with CD4 T-cell count of patients. Unstimulated neutrophils express high levels of surface Gal-9 that is bound to CD44, and, upon stimulation, neutrophils depalmitoylate CD44 and induce its movement out of the lipid raft. This process causes the release of Gal-9 from the surface of neutrophils. In addition, we found that neutrophil-derived exogenous Gal-9 binds to cell surface CD44 on T cells, which promotes LCK activation and subsequently enhances T-cell activation. Furthermore, this process was regulated by glycolysis and can be inhibited by interleukin (IL)-10. Together, our data reveal a novel mechanism of Gal-9 shedding from the surface of neutrophils. This could explain elevated plasma Gal-9 levels in HIV-infected individuals as an underlying mechanism of the well-characterized chronic immune activation in HIV infection. This study provides a novel role for the Gal-9 shedding from neutrophils. We anticipate that our results will spark renewed investigation into the role of neutrophils in T-cell activation in other acute and chronic conditions, as well as improved strategies for modulating Gal-9 shedding.

scholarly journals Relationship between T Cell Activation and CD4+T Cell Count in HIV‐Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of Therapy

2008 ◽  
Vol 197 (1) ◽  
pp. 126-133 ◽  
Author(s):  
Peter W. Hunt ◽  
Jason Brenchley ◽  
Elizabeth Sinclair ◽  
Joseph M. McCune ◽  
Michelle Roland ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Count ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Hiv Rna ◽  
Undetectable Plasma ◽  
Hiv Seropositive ◽  
Cd4 T Cell Count ◽  
Rna Levels

scholarly journals Physician Decisions to Defer Antiretroviral Therapy in Key Populations: Implications for Reducing Human Immunodeficiency Virus Incidence and Mortality in Malaysia

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Enrico G. Ferro ◽  
Gabriel J. Culbert ◽  
Jeffrey A. Wickersham ◽  
Ruthanne Marcus ◽  
Alana D. Steffen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
People Who Inject Drugs ◽  
Cd4 T Cell ◽  
Key Populations ◽  
Incidence And Mortality ◽  
Immunodeficiency Virus ◽  
Cd4 T Cell Count

Abstract Background Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. Methods Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV. Results The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8–36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5–5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44–.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34–.57) were significantly less likely to have ART deferred. Conclusions Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence-based treatment guidelines.

scholarly journals Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion

2019 ◽  
Vol 221 (7) ◽  
pp. 1135-1145 ◽  
Author(s):  
Genevieve E Martin ◽  
Matthew Pace ◽  
Freya M Shearer ◽  
Eva Zilber ◽  
Jacob Hurst ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Hiv Infection ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Hiv Dna ◽  
Art Initiation ◽  
Immunodeficiency Virus

Abstract Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet−Eomes− subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

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