scholarly journals Strong Human Immunodeficiency Virus (HIV)–Specific CD4+T Cell Responses in a Cohort of Chronically Infected Patients Are Associated with Interruptions in Anti‐HIV Chemotherapy

2000 ◽  
Vol 181 (4) ◽  
pp. 1264-1272 ◽  
Author(s):  
Patrick A. J. Haslett ◽  
Douglas F. Nixon ◽  
Zhu Shen ◽  
Marie Larsson ◽  
William I. Cox ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Anti Hiv

scholarly journals Transient Mobilization of Human Immunodeficiency Virus (HIV)-Specific CD4 T-Helper Cells Fails To Control Virus Rebounds during Intermittent Antiretroviral Therapy in Chronic HIV Type 1 Infection

2001 ◽  
Vol 75 (1) ◽  
pp. 234-241 ◽  
Author(s):  
Guislaine Carcelain ◽  
Roland Tubiana ◽  
Assia Samri ◽  
Vincent Calvez ◽  
Constance Delaugerre ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Virus Production ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Helper Cells ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT Immune control of human immunodeficiency virus (HIV) is not restored by highly active antiretroviral therapies (HAART) during chronic infection. We examined the capacity of repeated structured therapeutic interruptions (STI) to restore HIV-specific CD4 and CD8 T-cell responses that controlled virus production. Eleven STI (median duration, 7 days; ranges, 4 to 24 days) were performed in three chronically HIV-infected patients with CD4 counts above 400/mm3 and less than 200 HIV RNA copies/ml after 18 to 21 months of HAART; treatment resumed after 1 week or when virus became detectable. HIV-specific T-cell responses were analyzed by proliferation, gamma interferon (IFN-γ) production, and enzyme-linked immunospot assays. Seven virus rebounds were observed (median, 4,712 HIV-1 RNA copies/ml) with a median of 7 days during which CD4 and CD8 counts did not significantly change. After treatment resumed, the viral load returned below 200 copies/ml within 3 weeks. Significant CD4 T-cell proliferation and IFN-γ production against HIV p24 appeared simultaneously with or even before the virus rebounds in all patients. These CD4 responses lasted for less than 3 weeks and disappeared before therapeutic control of the virus had occurred. Increases in the numbers of HIV-specific CD8 T cells were delayed compared to changes in HIV-specific CD4 T-cell responses. No delay or increase in virus doubling time was observed after repeated STI. Iterative reexposure to HIV during short STI in chronically infected patients only transiently mobilized HIV-specific CD4 T1-helper cells, which might be rapidly altered by virus replication. Such kinetics might explain the failure at delaying subsequent virus rebounds and raises concerns about strategies based on STI to restore durable HIV-specific T-cell responses in chronic HIV infection.

scholarly journals Identification of human immunodeficiency virus-1 specific CD8+ and CD4+ T cell responses in perinatally-infected infants and their mothers

AIDS ◽  
2009 ◽  
Vol 27 (7) ◽  
pp. 789-798 ◽  
Author(s):  
Sharon Shalekoff ◽  
Stephen Meddows-Taylor ◽  
Glenda E Gray ◽  
Gayle G Sherman ◽  
Ashraf H Coovadia ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Perinatally Infected ◽  
Human Immunodeficiency Virus 1

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 A High Viral Burden Predicts the Loss of CD8 T-Cell Responses Specific for Subdominant Gag Epitopes during Chronic Human Immunodeficiency Virus Infection

2007 ◽  
Vol 81 (24) ◽  
pp. 13809-13815 ◽  
Author(s):  
Christof Geldmacher ◽  
Clive Gray ◽  
Martha Nason ◽  
Jeffrey R. Currier ◽  
Antelmo Haule ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Baseline Viral Load ◽  
Viral Control ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus (HIV)-specific CD8 T-cell responses targeting products encoded within the Gag open reading frame have frequently been associated with better viral control and disease outcome during the chronic phase of HIV infection. To further clarify this relationship, we have studied the dynamics of Gag-specific CD8 T-cell responses in relation to plasma viral load and time since infection in 33 chronically infected subjects over a 9-month period. High baseline viral loads were associated with a net loss of breadth (P < 0.001) and a decrease in the total magnitude of the Gag-specific T-cell response in general (P = 0.03). Most importantly, the baseline viral load predicted the subsequent change in the breadth of Gag recognition over time (P < 0.0001, r 2 = 0.41). Compared to maintained responses, lost responses were low in magnitude (P < 0.0001) and subdominant in the hierarchy of Gag-specific responses. The present study indicates that chronic exposure of the human immune system to high levels of HIV viremia is a determinant of virus-specific CD8 T-cell loss.

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