Clinical trial NCT03767465: Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer
Official title: Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infection
Cancer
Keywords: HIV
Cancer
Checkpoint inhibitors
HIV reservoir
Immunity
Lead sponsor: IrsiCaixa
Sponsor class: OTHER
First posted: 2018-12-06
Enrollment: 1
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: OTHER
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

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.

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

Primary outcomes:
measure: Quantification of total HIV DNA
timeFrame: At the end of recruitment (up to one year after inclusion)
measure: Quantification of cell-associated HIV RNA
timeFrame: At the end of recruitment (up to one year after inclusion)
measure: Quantification of ultrasensitive HIV viral load
timeFrame: At the end of recruitment (up to one year after inclusion)
measure: Analysis of changes in HIV-specific cellular responses
timeFrame: At the end of recruitment (up to one year after inclusion)
measure: Analysis of changes in immune-phenotype of cellular populations
timeFrame: At the end of recruitment (up to one year after inclusion)
measure: Analysis of changes in HIV inhibition capacity in vitro
timeFrame: At the end of recruitment (up to one year after inclusion)
measure: Supervision of changes on the standard blood analysis for oncologic follow-up
timeFrame: At the end of recruitment (up to one year after inclusion)
measure: Analysis of changes in imaging of the oncological focus
timeFrame: At the end of recruitment (up to one year after inclusion)
Secondary outcomes:
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
Study officials:
affiliation: IrsiCaixa
name: Javier Martinez-Picado, PhD
role: PRINCIPAL_INVESTIGATOR
References: