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

NCT ID: NCT03767465

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-10-26
• Study Completion Date: 2019-10-11

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.

Detailed Description

Long-lived latently infected resting CD4+ T cells are the main reason why current antiretroviral therapy (ART) is unable to cure HIV infection. Recent work has suggested that the expression of immune checkpoint markers, such as the programmed death-1 (PD1) or the cytotoxic T-lymphocyte antigen 4 (CTL-4), may play a role in viral persistence on ART via either suppression of virus transcription and/or reduced HIV-specific T cell activity, but the in vivo role of immune checkpoint markers in HIV persistence on ART is not clear.

Immunological checkpoint inhibitors are humanized monoclonal Immunoglobulin G (IgG) antibodies directed against several cell surface receptors, including PD-1 that inhibits binding of PD-1, expressed on activated T cells to its ligands PD-L1, overexpressed on certain cancer cells, and PD-L2, which is primarily expressed on antigen presenting cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity antigen presenting cells. Immunological checkpoint inhibitors can also target CTL-4, which is constitutively expressed in Treg cells but only upregulated in conventional T cells after activation, a phenomenon which is particularly notable in cancers. These drugs are used to treat oncology diseases, including metastatic melanoma, and have been associated with multiple changes in immune function thought to enhance antitumor T cell function.

This exploratory study will include HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated. The study is conceptually observational as the patients will be in regular clinical treatment with immunological checkpoint inhibitors for oncological conditions.

Conditions

HIV Infection; Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

PembroHIV

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• None

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IrsiCaixa

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Martinez-Picado, PhD

Role: PRINCIPAL_INVESTIGATOR

IrsiCaixa

Locations

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Countries

Spain

Other Identifiers

PembroHIV

Identifier Type: -

Identifier Source: org_study_id