Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer

NCT03767465 | Completed

• 1 other identifier: PembroHIV
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

It has been reported that peripheral and lymph node resident Cluster of Differentiation 4 (CD4)+ T cells expressing Programmed cell death protein 1 (PD-1) contribute to Human Immunodeficiency Virus (HIV) persistence during Antiretroviral Therapy (ART). In HIV-infected individuals, PD-1 expression on CD4+ T cells correlates with HIV disease progression, and loss of HIV-specific CD4+ T cell function can be reversed in vitro by PD-1 blockade. There are only a limited number of case reports describing the evolution of HIV-infected patients with concurrent oncological disease treated with immunological checkpoint inhibitors. However, this case provides very limited information on the effect of pembrolizumab on the HIV reservoir. Here, the investigators aim at describing changes in the HIV reservoir and in the HIV-specific immunity in HIV-infected patients on ART who receive immunological checkpoint inhibitors for the treatment of cancer, especially for metastatic melanoma.

Conditions

HIV Infection; Cancer

Keywords

HIV; Cancer; Checkpoint inhibitors; HIV reservoir; Immunity

Outcome Measures

Primary Outcomes (8)

• Quantification of total HIV DNA

  Measurement of HIV viral latency by quantification of total HIV DNA in purified CD4+ T cells, using digital droplet PCR (ddPCR)

  At the end of recruitment (up to one year after inclusion)

• Quantification of cell-associated HIV RNA

  Measurement of viral transcription by quantification of cell-associated unspliced HIV RNA in purified CD4+ T cells, using ddPCR

  At the end of recruitment (up to one year after inclusion)

• Quantification of ultrasensitive HIV viral load

  Measurement of ultrasensitive viremia in plasma using single copy assay

  At the end of recruitment (up to one year after inclusion)

• Analysis of changes in HIV-specific cellular responses

  Changes in the ability of Peripheral Blood Mononuclear Cells (PBMCs) to release Interferon gamma (IFNγ) in response to viral antigen stimulation (ELISPOT assay).

  At the end of recruitment (up to one year after inclusion)

• Analysis of changes in immune-phenotype of cellular populations

  Study of changes in multiple cell membrane markers related with cell function, including T-cell activation and proliferation, T-cell exhaustion, T-cell subpopulations and release of specific cytokines in response to HIV stimuli (multicolor flow cytometry).

  At the end of recruitment (up to one year after inclusion)

• Analysis of changes in HIV inhibition capacity in vitro

  Changes in the ex vivo ability of cluster of differentiation 8 (CD8)+ T cells to inhibit superinfected autologous CD4+ T cells (virus inhibition assay).

  At the end of recruitment (up to one year after inclusion)

• Supervision of changes on the standard blood analysis for oncologic follow-up

  Blood analysis will be revised for oncologic follow-up

  At the end of recruitment (up to one year after inclusion)

• Analysis of changes in imaging of the oncological focus

  Positron Emission Tomography (PET) scan will be analyzed for oncologic follow-up

  At the end of recruitment (up to one year after inclusion)

Study Arms (1)

PembroHIV

HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated

You may qualify if:

• HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated

You may not qualify if:

• None

Sponsors & Collaborators

• IrsiCaixa: lead

Study Sites (1)

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Criopreserved peripheral blood mononuclear cells (PBMCs) Frozen plasma

MeSH Terms

Conditions

HIV Infections; Neoplasms

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Javier Martinez-Picado, PhD

  IrsiCaixa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 6, 2018
• Study Start: October 26, 2018
• Primary Completion: March 18, 2019
• Study Completion: October 11, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

ES (1)