scholarly journals MAVS Genetic Variation Is Associated with Decreased HIV-1 Replication In Vitro and Reduced CD4+ T Cell Infection in HIV-1-Infected Individuals

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 764
Author(s):  
Melissa Stunnenberg ◽  
Lisa van Pul ◽  
Joris K. Sprokholt ◽  
Karel A. van Dort ◽  
Sonja I. Gringhuis ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Viral Load ◽  
T Cell ◽  
Viral Replication ◽  
Mononuclear Cells ◽  
Cd4 T Cell ◽  
Lower Percentage ◽  
Cell Counts ◽  
Hiv 1

The mitochondrial antiviral protein MAVS is a key player in the induction of antiviral responses; however, human immunodeficiency virus 1 (HIV-1) is able to suppress these responses. Two linked single nucleotide polymorphisms (SNPs) in the MAVS gene render MAVS insensitive to HIV-1-dependent suppression, and have been shown to be associated with a lower viral load at set point and delayed increase of viral load during disease progression. Here, we studied the underlying mechanisms involved in the control of viral replication in individuals homozygous for this MAVS genotype. We observed that individuals with the MAVS minor genotype had more stable total CD4+ T cell counts during a 7-year follow up and had lower cell-associated proviral DNA loads. Genetic variation in MAVS did not affect immune activation levels; however, a significantly lower percentage of naïve CD4+ but not CD8+ T cells was observed in the MAVS minor genotype. In vitro HIV-1 infection of peripheral blood mononuclear cells (PBMCs) from healthy donors with the MAVS minor genotype resulted in decreased viral replication. Although the precise underlying mechanism remains unclear, our data suggest that the protective effect of the MAVS minor genotype may be exerted by the initiation of local innate responses affecting viral replication and CD4+ T cell susceptibility.

Distribution of HIV-1 Plasma RNA Viral Load and CD4 + T-Cell Counts Among HIV-Infected Africans Evaluated for Antiretroviral Therapy

2001 ◽  
Vol 28 (1) ◽  
pp. 99-101 ◽  
Author(s):  
John N. Nkengasong ◽  
Marie-Yolande Borget ◽  
Chantal Maurice ◽  
Emmanuel Boateng ◽  
Mireille Kalou ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Plasma Rna ◽  
Hiv 1

scholarly journals Cluster of differentiation 4+ T-cell counts and human immunodeficiency virus-1 viral load in patients coinfected with hepatitis B virus and hepatitis C virus

2018 ◽  
Vol 10 (02) ◽  
pp. 162-167
Author(s):  
Sakshee Gupta ◽  
Bharti Malhotra ◽  
Jitendra Kumar Tiwari ◽  
Prabhu Dayal Khandelwal ◽  
Rakesh Kumar Maheshwari
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Hepatitis B ◽  
Cd4 T Cell ◽  
Hiv Viral Load ◽  
Cell Counts ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Cluster Of Differentiation ◽  
Hiv 1

ABSTRACT BACKGROUND: Coinfections of human immunodeficiency virus (HIV) with hepatitis viruses may affect the progress of disease and response to therapy. OBJECTIVES: To study the incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfections in HIV–positive patients and their influence on HIV–1 viral load and cluster of differentiation 4+ (CD4+) T–cell counts. MATERIALS AND METHODS: This pilot study was done on 179 HIV–positive patients attending antiretroviral therapy (ART) centre. Their blood samples were tested for HIV-1 viral load, CD4+ T–cell counts, hepatitis B surface antigen, anti–HCV antibodies, HBV DNA and HCV RNA polymerase chain reaction. RESULTS: Among the 179 patients, 7.82% (14/179) were coinfected with HBV and 4.46% (8/179) with HCV. Median CD4+ T–cell count of HIV monoinfected patients was 200 cells/µl and viral load was 1.67 log10 copies/µl. Median CD4+ T–cell counts of 193 cells/µl for HBV (P = 0.230) and 197 cells/µl for HCV (P = 0.610) coinfected patients were similar to that of HIV monoinfected patients. Viral load was higher in both HBV and HCV infected patients but statistically significant only for HCV (P = 0.017). Increase in CD4+ T–cell counts and decrease in HIV–1 viral load in coinfected patients on 2 years of ART were lower than that in HIV monoinfected patients. CONCLUSION: HBV/HCV coinfected HIV patients had similar CD4+ T–cell counts as in HIV monoinfected patients, higher HIV viral load both in chemo–naive patients and in those on ART as compared to HIV monoinfected patients. However, this study needs to be done on a large scale to assess the impact of coinfection on CD4 count and HIV viral load with proper follow–up of patients every 6 months till at least 2 years.

scholarly journals Reconstitution of Peripheral T Cells by Tissue-Derived CCR4+ Central Memory Cells Following HIV-1 Antiretroviral Therapy

2016 ◽  
Vol 1 (2) ◽  
pp. 260 ◽  
Author(s):  
Yolanda D. Mahnke ◽  
Kipper Fletez-Brant ◽  
Irini Sereti ◽  
Mario Roederer
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd8 T Cells ◽  
Plasma Viral Load ◽  
Cd4 T Cell ◽  
Cell Numbers ◽  
Cell Counts ◽  
Hiv 1

Background. Highly active antiretroviral therapy induces clinical benefits to HIV-1 infected individuals, which can be striking in those with progressive disease. Improved survival and decreased incidence of opportunistic infections go hand in hand with a suppression of the plasma viral load, an increase in peripheral CD4+ T-cell counts, as well as a reduction in the activation status of both CD4+ and CD8+ T cells.Methods. We investigated T-cell dynamics during ART by polychromatic flow cytometry in total as well as in HIV-1-specific CD4+ and CD8+ T cells. We also measured gene expression by single cell transcriptomics to assess functional state.Results. The cytokine pattern of HIV-specific CD8+ T cells was not altered after ART, though their magnitude decreased significantly as the plasma viral load was suppressed to undetectable levels. Importantly, while CD4+ T cell numbers increased substantially during the first year, the population did not normalize: the increases were largely due to expansion of mucosal-derived CCR4+ CD4+ TCM; transcriptomic analysis revealed that these are not classical Th2-type cells.Conclusion. The apparent long-term normalization of CD4+ T-cell numbers following ART does not comprise a normal balance of functionally distinct cells, but results in a dramatic Th2 shift of the reconstituting immune system.

scholarly journals Distribution of HIV-1 Plasma RNA Viral Load and CD4 + T-Cell Counts Among HIV-Infected Africans Evaluated for Antiretroviral Therapy

2001 ◽  
Vol 28 (1) ◽  
pp. 99-101
Author(s):  
John N. Nkengasong ◽  
Marie-Yolande Borget ◽  
Chantal Maurice ◽  
Emmanuel Boateng ◽  
Mireille Kalou ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Plasma Rna ◽  
Hiv 1

scholarly journals In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Omalla A. Olwenyi ◽  
Bannet Asingura ◽  
Prossy Naluyima ◽  
Godwin Upoki Anywar ◽  
Justine Nalunga ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
T Cell Activation ◽  
Azadirachta Indica ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Hla Dr ◽  
Hiv 1 ◽  
Hiv Negative

Abstract Background In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation. Methods Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated. Results Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups. Conclusion A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.

scholarly journals Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals

2018 ◽  
Vol 34 (10) ◽  
Author(s):  
Ingridt Hildegard Vogler ◽  
Daniela Frizon Alfieri ◽  
Heloisa Damazio Bruna Gianjacomo ◽  
Elaine Regina Delicato de Almeida ◽  
Edna Maria Vissoci Reiche
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Abstract: The latest Brazilian guideline recommended the reduction of routine CD4+ T cell counts for the monitoring of patients with human immunodeficiency virus type 1 (HIV-1) under combination antiretroviral therapy (cART). The aim of this study was to evaluate the safety of monitoring response to cART in HIV-1 infection using routine viral load at shorter intervals and CD4+ T cell count at longer intervals. CD4+ T cell counts and HIV-1 viral load were evaluated in 1,906 HIV-1-infected patients under cART during a three-year follow-up. Patients were stratified as sustained, non-sustained and non-responders. The proportion of patients who showed a CD4+ T > 350cells/µL at study entry among those with sustained, non-sustained and non-responders to cART and who remained with values above this threshold during follow-up was 94.1%, 81.8% and 71.9%, respectively. HIV-1-infected patients who are sustained virologic responders and have initial CD4+ T cell counts > 350cells/µL showed a higher chance of maintaining the counts of these cells above this threshold during follow-up than those presenting CD4+ T ≤ 350cells/µL (OR = 39.9; 95%CI: 26.5-60.2; p < 0.001). This study showed that HIV-1-infected patients who had sustained virologic response and initial CD4+ T > 350cells/µL were more likely to maintain CD4+ T cell counts above this threshold during the next three-year follow-up. This result underscores that the evaluation of CD4+ T cell counts in longer intervals does not impair the safety of monitoring cART response when routine viral load assessment is performed in HIV-1-infected patients with sustained virologic response.

scholarly journals Increased Plasma Levels of the TH2 chemokine CCL18 associated with low CD4+ T cell counts in HIV-1-infected Patients with a Suppressed Viral Load

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Prashant Malhotra ◽  
Patrick Haslett ◽  
Barbara Sherry ◽  
David H. Shepp ◽  
Paul Barber ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Plasma Levels ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv 1

scholarly journals Chronic Immune Activation and CD4+ T Cell Lymphopenia in Healthy African Individuals: Perspectives for SARS-CoV-2 Vaccine Efficacy

2021 ◽  
Vol 12 ◽  
Author(s):  
Dawit Wolday ◽  
Francis M. Ndungu ◽  
Gloria P. Gómez-Pérez ◽  
Tobias F. Rinke de Wit
Keyword(s):  
T Cell ◽  
Immune Activation ◽  
Mononuclear Cells ◽  
Parasitic Infections ◽  
Chronic Immune Activation ◽  
Activation Markers ◽  
Cell Counts ◽  
Hla Dr ◽  
Hiv 1

Chronic immune activation has been considered as the driving force for CD4+ T cell depletion in people infected with HIV-1. Interestingly, the normal immune profile of adult HIV-negative individuals living in Africa also exhibit chronic immune activation, reminiscent of that observed in HIV-1 infected individuals. It is characterized by increased levels of soluble immune activation markers, such as the cytokines interleukin (IL)-4, IL-10, TNF-α, and cellular activation markers including HLA-DR, CD-38, CCR5, coupled with reduced naïve and increased memory cells in CD4+ and CD8+ subsets. In addition, it is accompanied by low CD4+ T cell counts when compared to Europeans. There is also evidence that mononuclear cells from African infants secrete less innate cytokines than South and North Americans and Europeans in vitro. Chronic immune activation in Africans is linked to environmental factors such as parasitic infections and could be responsible for previously observed immune hypo-responsiveness to infections and vaccines. It is unclear whether the immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines will also be reduced by similar mechanisms. A review of studies investigating this phenomenon is urgently required as they should inform the design and delivery for vaccines to be used in African populations.

scholarly journals Association of -308 TNF-alpha promoter polymorphism with viral load and CD4 T-helper cell apoptosis in HIV-1 infected black South Africans

2012 ◽  
Vol 13 (2) ◽  
Author(s):  
Shivona Gounden ◽  
Devapregasan Moodley ◽  
Anil Chuturgoon ◽  
Leshern Karamchand ◽  
Halima Dawood
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Cell Apoptosis ◽  
Promoter Polymorphism ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv Progression ◽  
Increased Risk ◽  
Tnf Α ◽  
Hiv 1

Objective. To determine whether the -308 TNF-α promoter polymorphism is associated with markers of HIV progression in the South African population. Methods. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the -308 TNF-α polymorphism in 75 patients and 76 healthy controls. Serum TNF-α concentrations were measured using ELISA in each cohort. CD4+ T cell apoptosis and HIV-1 RNA viral load were determined using Annexin-V-FITC assay and Nuclisens Easy Q HIV-1 assay respectively. CD4 + T cell counts were measured flow cytometrically. Results. The frequency of -308 G allele was similar in the HIV-1 and control cohorts. The -308GG genotype was associated with lower TNF-α concentrations and markers of increased HIV progression indicated by higher TH lymphocyte apoptosis, lower TH lymphocyte count and higher plasma viral load, irrespective of treatment. Conclusion. The presence of the TNF-α -308 G allele in HIV-1 patients may be associated with increased risk of HIV-1 progression. Further research is required to investigate the nature of this association. S Afr J HIV Med 2012;13(2):72-77.

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