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

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.

Download Full-text

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

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa294 ◽

2020 ◽

Vol 222 (11) ◽

pp. 1837-1842 ◽

Cited By ~ 1

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.

Download Full-text

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

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy668 ◽

2019 ◽

Vol 219 (9) ◽

pp. 1407-1417 ◽

Cited By ~ 1

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.

Download Full-text

Functional T Cell Reconstitution and Human Immunodeficiency Virus–1–Specific Cell‐Mediated Immunity during Highly Active Antiretroviral Therapy

The Journal of Infectious Diseases ◽

10.1086/314837 ◽

1999 ◽

Vol 180 (1) ◽

pp. 76-86 ◽

Cited By ~ 88

Author(s):

Oscar Pontesilli ◽

Susana Kerkhof‐Garde ◽

Daan W. Notermans ◽

Norbert A. Foudraine ◽

Marijke T. L. Roos ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Cell Mediated Immunity ◽

Specific Cell ◽

Highly Active ◽

T Cell Reconstitution ◽

Immunodeficiency Virus ◽

Human Immunodeficiency Virus 1

Download Full-text

Long-Term Specific Immune Responses Induced in Humans by a Human Immunodeficiency Virus Type 1 Lipopeptide Vaccine: Characterization of CD8+-T-Cell Epitopes Recognized

Journal of Virology ◽

10.1128/jvi.77.20.11220-11231.2003 ◽

2003 ◽

Vol 77 (20) ◽

pp. 11220-11231 ◽

Cited By ~ 55

Author(s):

Hanne Gahéry-Ségard ◽

Gilles Pialoux ◽

Suzanne Figueiredo ◽

Céline Igéa ◽

Mathieu Surenaud ◽

...

Keyword(s):

Immune Response ◽

Human Immunodeficiency Virus ◽

T Cell ◽

T Cell Responses ◽

T Cell Epitopes ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone or with QS21 adjuvant to 28 HIV-uninfected volunteers. One month later, after a fourth injection of the vaccine, B- and T-cell anti-HIV responses were detected in >85% of the vaccinated volunteers. One year after this injection, a long-term immune response was observed in >50% of the volunteers. At this point, a positive QS21 effect was observed only in the sustained B-cell and CD4+-T-cell responses. To better characterize the CD8+-T-cell response, we used a gamma interferon enzyme-linked immunospot method and a bank of 59 HIV-1 epitopes. For the six most common HLA molecules (HLA-A2, -A3, -A11, -A24, -B7 superfamily, and -B8), an average of 10 (range, 3 to 15) HIV-1 epitopes were tested. CD8+-T-cell responses were evaluated according to the HLA class I molecules of the volunteers. Each assessment was based on 18 HIV-1 epitopes in average. We showed that 31 HIV-1 epitopes elicited specific CD8+-T-cell responses after vaccination. The most frequently recognized peptides were Nef 68-76 (-B7), Nef 71-79 (-B7), Nef 84-92 (-A11), Nef 135-143 (-B7), Nef 136-145 (-A2), Nef 137-145 (-A2), Gag 259-267 (-B8), Gag 260-268 (-A2), Gag 267-274 (-A2), Gag 267-277 (-B7), and Gag 276-283 (A24). We found that CD8+-T-cell epitopes were induced at a higher number after a fourth injection (P < 0.05 compared to three injections), which indicates an increase in the breadth of HIV CD8+-T-cell epitope recognition after the boost.

Download Full-text