Co-adaptation Between Human Immunodeficiency Virus (HIV) and Cluster of Differentiation 8 (CD8) Cellular Immunity ("ImmunoCo27")

Study of Co-adaptation Between Human Immunodeficiency Virus (HIV) and Cluster of Differentiation 8 (CD8) Cellular Immunity, for 27 Years of Natural Evolution and on Treatment

The objective is to characterize the viral evolution and viral factors determining HIV virulence, the evolution of the HIV reservoir in PBMC and the co-evolution of anti-HIV CD8 T cell repertoires. The coordinated study of virus evolution, host responses and identification of genetic determinants of virulence should allow to better understand mechanisms of HIV pathogenicity and persistence of mutations in viral reservoirs.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Other: Non interventional study

Detailed Description

The importance of the still unmet challenges raised by researches on the eradication of the HIV reservoirs and by the need for developing efficient vaccines against HIV, imposes a much deeper understanding the molecular mechanisms regulating the co-evolution and the co-adaptation between HIV and its host during the natural course of the disease an during treatment. The unique cell collection established 27 years ago in an ANRS cohort (ImmunoCo) and the new methods of ultra deep sequencing, or " next generation sequencing", allow to produce innovative analysis of the HIV variability and of reservoirs as well as of the repertoires used by CD8 T cells responses to provide new insights in the very long term relationships between the virus and its host. The objective is to progress at unprecedented levels in the understanding of these mechanisms thanks to the unique opportunity offered by this Immunoco cohort initially composed of 152 patients infected by HIV, most of them untreated when recruited from 1991 to 97 at Pitié-Salpêtrière hospital, with 28 subjects still followed in this hospital and efficiently treated for the last 15 years. The ImmunoCo cohort had initially been set up to study the characteristics of the cytotoxic T lymphocyte (CTL) responses to HIV with disease progression. This exceptional and still available 1991-97 cell collection enriched of extra samples from 1988 to nowadays, allow us to perform a retrospective longitudinal analysis over 27 years in the 28 patients still followed-up, with a new blood sampling in 2016. The project involves 5 highly experienced teams and aims at characterizing in parallel: 1) the viral evolution and viral factors determining virulence, as markers predicting progression of infection, by performing an ultra deep sequencing of the whole HIV genome and of viral variants archived in blood mononuclear cells (PBMC), and 2) the evolution of the reservoir in PBMC and of the distribution of variants archived in those reservoirs over time, in relationship with exposure to the various selective pressures due to CTL or antiretroviral therapy (ART), 3) the co-evolution of anti-HIV CD8 T cell repertoires: the hypothesis is that the emergence of new CD8 T clonotypes displaying a great sensibility for variant antigens, or a cross-reactivity able to recognize similarly wild-type and mutant epitopes allow an efficient long term control of viral replication, and that cell loss by clonal exhaustion is associated to disease progression. The coordinated study of virus evolution, host responses and identification of genetic determinants of virulence should allow to better understand mechanisms of HIV pathogenicity and persistence of mutations in viral reservoirs, especially of defective mutants or resistant mutants to ART, as well as the co-adaptation of CD8 T cell repertoires and of viral variability determining the capacities of viral control by anti-HIV CD8 T cells. Altogether these results should open new strategies for inhibiting viral replication and for controlling viral reservoirs for therapeutic and vaccinal perspectives.

• Study Type: Observational
• Enrollment (Actual): 22

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients infected with HIV included in the ANRS Immunoco cohort.

Description

Inclusion Criteria:

• Initially included in the ANRS Immunoco cohort and still followed in the Infectious Diseases department by Pr C. Katlama team

Exclusion Criteria:

• None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Longitudinal study of the co-adaptation of HIV and immune host factors in 28 patients with HIV followed for 27 years.	27 years

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Victor Appay, phD, INSERM S1136

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: August 29, 2016
• First Posted (Estimate): September 1, 2016

Study Record Updates

• Last Update Posted (Actual): September 28, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: HIV infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: ANRS EP60; 2016-A00400-51 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Scientific publication