scholarly journals Raltegravir Inclusion Decreases CD4 T-Cells Intra-Cellular Viral Load and Increases CD4 and CD28 Positive T-Cells in Selected HIV Patients

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 208
Author(s):  
Gaurav Kumar ◽  
Jacqueline Cottalorda-Dufayard ◽  
Rodolphe Garraffo ◽  
Francine De Salvador-Guillouët ◽  
Eric Cua ◽  
...  

Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and <500/mL were selected to receive RLT for 3 months from M0 to M3. Patients had 7 sequential viro-immunological determinations from M-1 to M5. Immune phenotypes were determined by flow cytometry and TID quantification was performed using PCR assay on purified cells. TID (median values) at the initiation of RLT in CD4 T-cells was 117 copies/millions of cells, decreased to 27.5 on M3, and remained thereafter permanently under the cut-off (<10 copies/millions of cells) in 4 out of 6 patients. This was associated with an increase of CD4 and CD4 + CD28+ T-cells and a decrease of HLA-DR expression and apoptosis of CD4 T-cells. RLT inclusion led to decreases in the viral load along with positive immune reconstitution, mainly for CD4 T-cells in HIV patients.

2017 ◽  
Vol 4 (2) ◽  
pp. 155-158
Author(s):  
Yanis Meddour ◽  
◽  
Imène Zerrouk ◽  
Fatma Zohra Souid ◽  
Mohamed Amine ◽  
...  

Introduction. HIV infection is characterized by an enhanced synthesis of cytokines and chemokines, a quantitative T cells disequilibrium and increased Turn over that signs a chronic activation of the immune system. Phenotype change in CD4+ T cells by over-expression of activation antigens CD38 and HLA-DR are suggested as markers of this process. Materials and methods. We investigated by four-color flow cytometry the expression of both activation markers on peripheral CD4+ T cells in 106 HIV-1 Algerian infected patients and 34 uninfected controls. Percentage’s expression of CD4+CD38+HLA-DR+ cells was compared with clinical stages, viral load and anti-retroviral treatment (ARV). Results. The proportion of CD4+ T cells coexpressing HLA-DR and CD38 was higher in infected patients than in controls (respectively, 14.2 % ± 3.6 vs. 5.8 % ± 4.1, P=0.01), in symptomatic HIV patients than asymptomatic (13 % ± 3 vs. 15.9 % ± 4.6, P=0.01) and followed viral load kinetics. In matched treated and untreated patients, activated CD4+T proportion does not show any statical difference (respectively, 13 % and 14 %, p=0.09). Conclusion. In our cohort, CD4+ T cells expressing CD38 and HLA-DR were associated with HIV infection and correlated with disease progression, regardless of ARV treatment. As CD4+ count and viral load, this lymphocyte subset may be an interesting disease evolution marker; its value remains to be determined in prognostic or as therapy response indicator.


Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 101 ◽  
Author(s):  
Mohamed Ahmed El-Mokhtar ◽  
Sherein G. Elgendy ◽  
Abeer Sharaf Eldin ◽  
Elham Ahmed Hassan ◽  
Ali Abdel Azeem Hasan ◽  
...  

The occurrence of tuberculosis (TB) and hepatitis C virus (HCV) infections in the same patient presents a unique clinical challenge. The impact of HCV infection on the immune response to TB remains poorly investigated in TB+/HCV+ patients. This study was conducted to evaluate the impact of HCV on the T-cell-mediated immune response to TB in coinfected patients. Sixty-four patients with active TB infections were screened for coinfection with HCV. The expression of immune activation markers IFN-γ, CD38, and HLA-DR on TB-specific CD4+ T cells was evaluated by flow cytometry in TB-monoinfected patients, TB/HCV-coinfected patients, and healthy controls. IL-2, IL-4, IFN-γ, TNF-α, and IL-10 levels were measured using ELISA. The end-of-treatment response to anti-TB therapy was recorded for both patient groups. Significantly lower levels of CD4+IFN-γ+CD38+ and CD4+IFN-γ+HLA-DR+ T cells were detected in TB/HCV-coinfected patients compared to TB monoinfected patients and controls. TB+/HCV+-coinfected patients showed higher serum levels of IL-10. The baseline frequencies of TB-specific activated T-cell subsets did not predict the response to antituberculous therapy in TB+/HCV+ patients. We concluded that different subsets of TB-specific CD4+ T cells in TB/HCV-infected individuals are partially impaired in early-stage HCV infection. This was combined with increased serum IL-10 level. Such immune modulations may represent a powerful risk factor for disease progression in patients with HCV/TB coinfection.


2012 ◽  
Vol 6 (09) ◽  
pp. 660-663 ◽  
Author(s):  
Daniel Nii Aryee Tagoe ◽  
Joseph Boachie

Introduction: The human immunodeficiency virus (HIV) and malaria destroy important cells required for proper immunological and haematological functioning of the body. This research therefore aimed to assess the effect of malaria on CD4+ and haemoglobin (Hb) levels of HIV-malaria co-infected patients. Methodology: The study was performed by sampling 220 adult HIV patients on highly active anti retroviral therapy (HAART) who routinely visited the Tema General Hospital in Ghana. Blood samples were obtained for both blood film microscopy identification of malaria parasites and analysis using rapid diagnostic test kits. A BD Facscount Analyzer was used in the quantification of CD4+ levels. Results: Of the 220 patients sampled, 34 (15.5%) were HIV-malaria co-infected, all of whom (34; 100%) had CD4+ counts below the normal range, while 23 (12.9%) of the HIV mono-infected patients had normal CD4+ counts. Almost all HIV-malaria co-infected patients (33; 97.1%) had low Hb levels, whereas 79 (42.5%) of the HIV mono-infected patients had normal Hb. Malaria infection strongly correlated positively and significantly with both low CD4+ count (χ2 = 0.828, P = 0.003) and Hb (χ2 = 0.817, P = 0.004) levels. Conclusion: Malaria co-infection with HIV decreases CD4+ T cells and Hb levels in patients. It is therefore recommended that HIV patients in malaria endemic areas should adhere to malaria preventive measures.


Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 119-131
Author(s):  
Jana Palmowski ◽  
Kristina Gebhardt ◽  
Thomas Reichel ◽  
Torsten Frech ◽  
Robert Ringseis ◽  
...  

CD4+ T cells are sensitive to peripheral changes of cytokine levels and metabolic substrates such as glucose and lactate. This study aimed to analyze whether factors released after exercise alter parameters of human T cell metabolism, specifically glycolysis and oxidative phosphorylation. We used primary human CD4+ T cells activated in the presence of autologous serum, which was collected before (CO) and after a 30-min exercise intervention (EX). In the course of activation, cells and supernatants were analyzed for cell viability and diameter, real-time oxygen consumption by using PreSens Technology, mRNA expression of glycolytic enzymes and complexes of the electron transport chain by real-time PCR, glucose, and lactate levels in supernatants, and in vitro differentiation by flow cytometry. EX did not alter T cell phenotype, viability, or on-blast formation. Similarly, no difference between CO and EX were found for CD4+ T cell activation and cellular oxygen consumption. In contrast, higher levels of glucose were found after 48 h activation in EX conditions. T cells activated in autologous exercise serum expressed lower HK1 mRNA and higher IFN-γ receptor 1. We suggest that the exercise protocol used was not sufficient to destabilize the immune metabolism of T cells. Therefore, more intense and prolonged exercise should be used in future studies.


2016 ◽  
Vol 29 (3) ◽  
pp. 176-183 ◽  
Author(s):  
Sara Tanaskovic ◽  
Sonia Fernandez ◽  
Henny Saraswati ◽  
Evy Yunihastuti ◽  
Rino A. Gani ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e19607 ◽  
Author(s):  
Hong He ◽  
Pramod N. Nehete ◽  
Bharti Nehete ◽  
Eric Wieder ◽  
Guojun Yang ◽  
...  

2020 ◽  
Author(s):  
Meropi Aravantinou ◽  
Olga Mizenina ◽  
Thilo Brill ◽  
Jessica Kenney ◽  
Christine Timmons ◽  
...  

ABSTRACTDevelopment of an effective human immunodeficiency virus (HIV) vaccine is among the highest priorities in the biomedical research agenda. Adjuvants enhance vaccine efficacy, but in the case of HIV, strong or inappropriate immune activation may undermine protection by increasing HIV susceptibility. Co-infection with immunomodulatory pathogens may also impact vaccine efficacy. In the rhesus macaque rectal SIVΔNef live attenuated vaccine model, we utilized a low virulence HSV-2 infection and the double-stranded RNA viral mimic polyICLC as tools to probe the effects of distinct types of immune activation on HIV vaccine efficacy and explore novel correlates of protection from wild type SIV. Rectally administered HSV-2 and polyICLC impacted the protection conferred by mucosal SIVΔNef vaccination by favoring partial protection in animals with breakthrough infection following virulent SIV challenge (“Controllers”). However, SIVΔNef persistence in blood and tissues did not predict protection in this rectal immunization and challenge model. Non-controllers had similar SIVΔNef viremia as completely protected macaques, and while they tended to have less replication competent SIVΔNef in lymph nodes, controllers had no recoverable virus in the lymph nodes. Non-controllers differed from protected macaques immunologically by having a greater frequency of pro-inflammatory CXCR3+CCR6+ CD4 T cells in blood and a monofunctional IFNγ-dominant CD8 T cell response in lymph nodes. Controller phenotype was associated with heightened IFNα production during acute SIV infection and a greater frequency of CXCR5+ CD4 T cells in blood pre-challenge despite a lower frequency of cells with the T follicular helper (Tfh) cell phenotype in blood and lymph nodes. Our results establish novel correlates of immunological control of SIV infection while reinforcing the potential importance of T cell functionality and location in SIVΔNef efficacy. Moreover, this work highlights that triggering of mucosal immunity can aid mucosal vaccine strategies rather than undermine protection.AUTHOR SUMMARYAn efficacious HIV vaccine is essential to contain the HIV pandemic. Vaccine-mediated protection from HIV may be either enhanced or obstructed by mucosal immune activation; thus, the impact of adjuvants and underlying co-infections that lead to immune activation needs to be evaluated. Using the SIV macaque model, we set out to study the impact of underlying infection with HSV-2 or treatment with the adjuvant polyICLC on rectal immunization with the live attenuated vaccine SIVΔNef. We found that neither stimulus impacted complete protection from SIV; however, the combination of HSV-2 and polyICLC improved control of infection in animals that were not completely protected. Compared with non-controller macaques, controllers had less inflammatory T cells before SIV challenge as well as greater gene expression of IFNα and more functional SIV-specific T cells after infection. The results add to our understanding of the mechanisms of SIVΔNef protection and demonstrate that mucosal immune activation does not necessarily undermine protection in mucosal vaccination against HIV.


2020 ◽  
Author(s):  
Thomas Vollbrecht ◽  
Aaron O. Angerstein ◽  
Bryson Menke ◽  
Nikesh M. Kumar ◽  
Michelli Faria Oliveira ◽  
...  

Abstract BackgroundA reservoir of replication-competent but latent virus is the main obstacle to a cure for HIV-infection. Much of this reservoir resides in memory CD4 T cells. We hypothesized that these cells can be reactivated with antigens from HIV and other common pathogens to reverse latency. ResultsWe obtained mononuclear cells from the peripheral blood of antiretroviral-treated patients with suppressed viremia. We tested pools of peptides and proteins derived from HIV and from other pathogens including CMV for their ability to reverse latency ex vivo by activation of memory responses. We assessed activation of the CD4 T cells by measuring the up-regulation of cell-surface CD69. We assessed HIV-expression using two assays: a real-time PCR assay for virion-associated viral RNA and a droplet digital PCR assay for cell-associated, multiply spliced viral mRNA. Reversal of latency occurred in a minority of cells from some participants, but no single antigen induced HIV-expression ex vivo consistently. When reversal of latency was induced by a specific peptide pool or protein, the extent was proportionally greater than that of T cell activation. ConclusionsIn this group of patients in whom antiretroviral therapy was started during chronic infection, the latent reservoir does not appear to consistently reside in CD4 T cells of a predominant antigen-specificity. Peptide-antigens reversed HIV-latency ex vivo with modest and variable activity. When latency was reversed by specific peptides or proteins, it was proportionally greater than the extent of T cell activation, suggesting partial enrichment of the latent reservoir in cells of specific antigen-reactivity.


2006 ◽  
Vol 119 ◽  
pp. S151
Author(s):  
Cristina Costantino ◽  
Hidde Ploegh ◽  
Clare Baecher-Allan ◽  
David Hafler
Keyword(s):  
T Cells ◽  

Author(s):  
Fahad Al-Majid ◽  
Zahid Shakoor ◽  
Mazin Barry

Background and Objectives. Variations in immune reconstitution following antiretroviral treatment (ART) among HIV patients have previously been observed. This study aims at assessing immune reconstitution after successful ART among HIV-infected Saudi patients.Methods. This retrospective study of 240 HIV-infected patients was performed between May 2010 and June 2015 in the HIV center at King Saud Hospital, Riyadh. Data were extracted for CD4, CD8 cell, and CD3/HLA-DR counts along with the viral load from patient records before and after four years of successful ART. The inclusion criterion was patients with CD4 reconstitution of either equal to or more than 400 cells/mm3with an undetectable HIV viral load following ART. Based on their presentation, the HIV patients were grouped into early treatment (ET) and delayed treatment (DT) groups with CD4 counts of 200–350 cells/mm3and less than 200 cells/mm3, respectively.Findings. The pretreatment CD8+ counts of median 865 cells/mm3(interquartile range (IQR) 774–1072) in the DT group declined to median 753 cells/mm3(IQR 574–987;p<0.0001). Moreover, there was a decline in CD8 counts from 703 cells/mm3(IQR 655–747) to 620 cells/mm3(IQR 563–645;p<0.04) in the ET group after four years of successful ART. Pretreatment activation marker (CD3/HLA-DR+) expression of median 29% in the DT group declined to 22% and in the ET group from a median of 23% to 19% after treatment. The CD4/CD8 ratio in the DT group increased from 0.14 (IQR 0.09–0.88) to 0.71 (IQR 0.54–0.9) and from 0.42 (IQR 0.35–0.55) to 0.87 (IQR 0.71–0.98) in the ET group.Conclusion. Immune reconstitution after successful ART among HIV-infected Saudi patients was associated with a CD8 T-cell population expansion with a suboptimal CD4/CD8 ratio and persistent immune activation. Early initiation of ART appears to favorably influence the CD4/CD8 ratio.


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