Co-adaptation Between HIV and CD8 Cellular Immunity

2016-09-01 14:53:21 | BioPortfolio


Our objective here 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.


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 and the new methods of ultradeep 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. Our 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, with 28 subjects still followed in our hospital and efficiently treated for the last 15 years. This cohort had initially been set up to study the characteristics of the cytotoxic T lymphopcyte (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 2015. Our 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 ultradeep 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 ARV, 3) the co-evolution of anti-HIV CD8 T cell repertoires: we will test the hypothesis 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 ARV, 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 Design

Observational Model: Cohort


HIV Infection


Non interventionnal study


Not yet recruiting


French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inser

Results (where available)

View Results


Published on BioPortfolio: 2016-09-01T14:53:21-0400

Clinical Trials [520 Associated Clinical Trials listed on BioPortfolio]

Study of Pentasa® for Reducing Residual Systemic Immune Activation in Treated HIV Infection

An open label study will be performed on 60 people with HIV infection who are maintained on effective treatment with antiretroviral drugs.

Study of Oral Papillomavirus In Teens and Twenties

Recently human papillomavirus (HPV) has been recognized to cause some oropharyngeal (tonsil) cancer. But very little is known about oral HPV infection and risk factors. This study will eva...

A Study Of The Safety, Tolerability And Effective Of Voriconazole For The Treatment Of Serious Candida Infection And Candida Infection Of The Throat In Pediatric Patients

The purpose of this study is to determine whether voriconazole is safe and effective for the treatment of serious Candida infection and Candida infection of the esophagus in children and a...

Scandinavian Cystic Fibrosis Azithromycin Study

In patients with Cystic Fibrosis, recurrent airway infection caused by Pseudomonas aeruginosa ultimately leads to chronic airway infection. The purpose of this study is to determine whethe...

The Epidemiology of Infection With Vancomycin-Resistant Enterococci

Current projects study veteran patients with chronic ulcers and MRSA colonization and infection, patients with imipenem-resistant P. aeruginosa colonization and infection, the relationship...

PubMed Articles [15304 Associated PubMed Articles listed on BioPortfolio]

Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study.

Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection a...

Do Trabecular Metal Acetabular Components Reduce the Risk of Rerevision After Revision THA Performed for Periprosthetic Joint Infection? A Study Using the NJR Data Set.

A single-center study of 144 THAs revised specifically for periprosthetic joint infection (PJI) observed that trabecular metal (TM) acetabular components had a reduced risk of rerevision for subsequen...

Observation study of water outlet design from a cross infection / user perspective; time for a radical re-think?

Hand washing is a key barrier to cross infection performed at a Hand Wash Station (HWS). Elbow-operated outlets if used incorrectly (with hands) become highly touched objects potentially providing a r...

Tuberculosis infection among the elderly in 20,486 rural residents aged 50-70 years old in Zhongmu County, China.

Elderly in rural China has been known to be at increased risk of contracting tuberculosis (TB) infection and developing active disease. This study aims to estimate the burden of TB infection and to id...

Progress in the elimination of hepatitis C virus infection: A population-based cohort study in Spain.

The World Health Organization set targets to eliminate hepatitis C virus (HCV) infection through detection and treatment of all cases by 2030. This study aimed to describe the progress and difficultie...

Medical and Biotech [MESH] Definitions

A work that reports on the results of a clinical study in which participants may receive diagnostic, therapeutic, or other types of interventions, but the investigator does not assign participants to specific interventions (as in an interventional study).

Work consisting of a controlled study executed by several cooperating institutions.

Infection by a variety of fungi, usually through four possible mechanisms: superficial infection producing conjunctivitis, keratitis, or lacrimal obstruction; extension of infection from neighboring structures - skin, paranasal sinuses, nasopharynx; direct introduction during surgery or accidental penetrating trauma; or via the blood or lymphatic routes in patients with underlying mycoses.

A study that compares a group of participants receiving an intervention with a similar group from the past who did not.

First-released version of study results in a series of data collection efforts used for the purpose of generating further interest in and or funding of a research study.

More From BioPortfolio on "Co-adaptation Between HIV and CD8 Cellular Immunity"

Quick Search


Relevant Topic

Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...

Searches Linking to this Trial