scholarly journals Impact of Antiretroviral Therapy and Changes in Virus Load on Human Immunodeficiency Virus (HIV)–Specific T Cell Responses in Primary HIV Infection

2003 ◽  
Vol 187 (5) ◽  
pp. 748-757 ◽  
Author(s):  
Christine Lacabaratz‐Porret ◽  
Alejandra Urrutia ◽  
Jean‐Marc Doisne ◽  
Cécile Goujard ◽  
Christiane Deveau ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
T Cell Responses ◽  
Primary Hiv Infection ◽  
Virus Load ◽  
Cell Responses ◽  
Immunodeficiency Virus

scholarly journals Maintenance of Viral Suppression in Human Immunodeficiency Virus Controllers Despite Waning T-Cell Responses During Antiretroviral Therapy

2020 ◽  
Vol 222 (11) ◽  
pp. 1837-1842 ◽  
Author(s):  
Nikolaus Jilg ◽  
Pilar Garcia-Broncano ◽  
Michael Peluso ◽  
Florencia P Segal ◽  
Ronald J Bosch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
T Cell Activation ◽  
Cell Activation ◽  
T Cell Responses ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Undetectable Viremia ◽  
Hiv Controllers

Abstract AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in human immunodeficiency virus (HIV) controllers start antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Before ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. During ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.

scholarly journals Differential Pathogen-Specific Immune Reconstitution in Antiretroviral Therapy-Treated Human Immunodeficiency Virus-Infected Children

2019 ◽  
Vol 219 (9) ◽  
pp. 1407-1417 ◽  
Author(s):  
Maximilian Muenchhoff ◽  
Emily Adland ◽  
Julia Roider ◽  
Henrik Kløverpris ◽  
Alasdair Leslie ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
T Cell Responses ◽  
Cell Phenotype ◽  
Memory Phenotype ◽  
Cell Responses ◽  
Immune Exhaustion ◽  
Immunodeficiency Virus

Abstract Background Susceptibility to coinfections in human immunodeficiency virus (HIV)-infected patients remains increased despite antiretroviral therapy (ART). To elucidate mechanisms involved in immune reconstitution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell responses in children before and after ART. Methods We prospectively enrolled 25 HIV-infected children to study HIV-, cytomegalovirus (CMV)-, and tuberculosis (TB)-specific T-cell responses before and 1 year after initiation of ART using intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays after in vitro stimulation. We further measured expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation. Results We observed differential, pathogen-specific changes after 1 year of ART in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased programmed cell death 1 (PD-1) expression. The proliferative capacity of HIV- and PPD-specific responses increased after 1 year of ART. Of note, the recovery of CMV- and TB-specific responses was correlated with a decrease in PD-1 expression (r = 0.83, P = .008 and r = 0.81, P = .0007, respectively). Conclusions Reconstitution of immune responses on ART is associated with alterations in T-cell phenotype, function, and PD-1 expression that are distinct for HIV, TB, and CMV. The PD-1 pathway represents a potential target for immunotherapy in HIV-infected patients on ART with insufficient immune reconstitution.

scholarly journals Analysis of Total Human Immunodeficiency Virus (HIV)-Specific CD4+ and CD8+ T-Cell Responses: Relationship to Viral Load in Untreated HIV Infection

2001 ◽  
Vol 75 (24) ◽  
pp. 11983-11991 ◽  
Author(s):  
Michael R. Betts ◽  
David R. Ambrozak ◽  
Daniel C. Douek ◽  
Sebastian Bonhoeffer ◽  
Jason M. Brenchley ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus (HIV)-specific T-cell responses are thought to play a key role in viral load decline during primary infection and in determining the subsequent viral load set point. The requirements for this effect are unknown, partly because comprehensive analysis of total HIV-specific CD4+ and CD8+T-cell responses to all HIV-encoded epitopes has not been accomplished. To assess these responses, we used cytokine flow cytometry and overlapping peptide pools encompassing all products of the HIV-1 genome to study total HIV-specific T-cell responses in 23 highly active antiretroviral therapy naı̈ve HIV-infected patients. HIV-specific CD8+ T-cell responses were detectable in all patients, ranging between 1.6 and 18.4% of total CD8+ T cells. HIV-specific CD4+ T-cell responses were present in 21 of 23 patients, although the responses were lower (0.2 to 2.94%). Contrary to previous reports, a positive correlation was identified between the plasma viral load and the total HIV-, Env-, and Nef-specific CD8+ T-cell frequency. No correlation was found either between viral load and total or Gag-specific CD4+ T-cell response or between the frequency of HIV-specific CD4+ and CD8+ T cells. These results suggest that overall frequencies of HIV-specific T cells are not the sole determinant of immune-mediated protection in HIV-infection.

scholarly journals Comparisons of CD8+ T Cells Specific for Human Immunodeficiency Virus, Hepatitis C Virus, and Cytomegalovirus Reveal Differences in Frequency, Immunodominance, Phenotype, and Interleukin-2 Responsiveness

2009 ◽  
Vol 83 (6) ◽  
pp. 2728-2742 ◽  
Author(s):  
Prasanna Jagannathan ◽  
Christine M. Osborne ◽  
Cassandra Royce ◽  
Maura M. Manion ◽  
John C. Tilton ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Hiv Infection ◽  
Interleukin 2 ◽  
T Cell Responses ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT To better understand the components of an effective immune response to human immunodeficiency virus (HIV), the CD8+ T-cell responses to HIV, hepatitis C virus (HCV), and cytomegalovirus (CMV) were compared with regard to frequency, immunodominance, phenotype, and interleukin-2 (IL-2) responsiveness. Responses were examined in rare patients exhibiting durable immune-mediated control over HIV, termed long-term nonprogressors (LTNP) or elite controllers, and patients with progressive HIV infection (progressors). The magnitude of the virus-specific CD8+ T-cell response targeting HIV, CMV, and HCV was not significantly different between LTNP and progressors, even though their capacity to proliferate to HIV antigens was preserved only in LTNP. In contrast to HIV-specific CD8+ T-cell responses of LTNP, HLA B5701-restricted responses within CMV pp65 were rare and did not dominate the total CMV-specific response. Virus-specific CD8+ T cells were predominantly CD27+45RO+ for HIV and CD27−45RA+ for CMV; however, these phenotypes were highly variable and heavily influenced by the degree of viremia. Although IL-2 induced significant expansions of CMV-specific CD8+ T cells in LTNP and progressors by increasing both the numbers of cells entering the proliferating pool and the number of divisions, the proliferative capacity of a significant proportion of HIV-specific CD8+ T cells was not restored with exogenous IL-2. These results suggest that immunodominance by HLA B5701-restricted cells is specific to HIV infection in LTNP and is not a feature of responses to other chronic viral infections. They also suggest that poor responsiveness to IL-2 is a property of HIV-specific CD8+ T cells of progressors that is not shared with responses to other viruses over which immunologic control is maintained.

scholarly journals Changes in Paracrine Interleukin-2 Requirement, CCR7 Expression, Frequency, and Cytokine Secretion of Human Immunodeficiency Virus-Specific CD4+ T Cells Are a Consequence of Antigen Load

2006 ◽  
Vol 81 (6) ◽  
pp. 2713-2725 ◽  
Author(s):  
John C. Tilton ◽  
Marlise R. Luskin ◽  
Alison J. Johnson ◽  
Maura Manion ◽  
Claire W. Hallahan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cytokine Production ◽  
Interleukin 2 ◽  
T Cell Responses ◽  
H3n2 Virus ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Virus-specific CD4+ T-cell responses are thought to be required for the induction and maintenance of many effective CD8+ T-cell and B-cell immune responses in experimental animals and humans. Although the presence of human immunodeficiency virus (HIV)-specific CD4+ T cells has been documented in patients at all stages of HIV infection, many fundamental questions regarding their frequency and function remain. A 10-color, 12-parameter flow cytometric panel was utilized to examine the frequency, memory phenotype (CD27, CCR7, and CD45RA), and cytokine production (interleukin-2 [IL-2], gamma interferon, and tumor necrosis factor alpha) of CD4+ T cells specific for HIV antigens as well as for adenovirus, Epstein-Barr virus (EBV), influenza H1N1 virus, influenza H3N2 virus, cytomegalovirus, varicella-zoster virus (VZV), and tetanus toxoid in normal controls, long-term nonprogressors (LTNP), and HIV-infected patients with progressive disease on or off therapy. The HIV-specific CD4+ T-cell responses in LTNP and patients on therapy were similar in frequency, phenotype, and cytokine production to responses directed against adenovirus, EBV, influenza virus, and VZV. HIV-specific CD4+ T cells from patients off antiretroviral therapy demonstrated a shift towards a CCR7− CD45RA− phenotype and a reduced percentage of IL-2-producing cells. The alterations in cytokine production during HIV viremia were found to be intrinsic to the HIV-specific CD4+ T cells and caused a requirement for IL-2 supplied exogenously for proliferation to occur. These observations suggest that many previously described changes in HIV-specific CD4+ T-cell function and phenotype are a consequence of high levels of antigen in viremic patients. In addition, defects in function and phenotype of HIV-specific CD4+ T cells are not readily discernible in the context of antiretroviral therapy but rather are similar to responses to other viruses.

scholarly journals Aviremia 10 Years Postdiscontinuation of Antiretroviral Therapy Initiated During Primary Human Immunodeficiency Virus-1 Infection and Association With Gag-Specific T-Cell Responses

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Sabine Kinloch-de Loes ◽  
Lucy Dorrell ◽  
Hongbing Yang ◽  
Gareth A. D. Hardy ◽  
Sabine Yerly ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Viral Reservoir ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Drug Free ◽  
Human Immunodeficiency Virus 1

Abstract Combination antiretroviral therapy during primary human immunodeficiency virus-1 infection may enable long-term drug-free virological control in rare individuals. We describe a female who maintained aviremia and a normal CD4+/CD8+ T cell ratio for 10 years after stopping therapy, despite a persistent viral reservoir. Cellular immune responses may have contributed to this outcome.

scholarly journals Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic Infection

2006 ◽  
Vol 80 (16) ◽  
pp. 8236-8247 ◽  
Author(s):  
Moraima Guadalupe ◽  
Sumathi Sankaran ◽  
Michael D. George ◽  
Elizabeth Reay ◽  
David Verhoeven ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Microarray Analysis ◽  
Dna Microarray ◽  
Peripheral Blood ◽  
Viral Suppression ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11α, αEβ7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

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