Role of PLA2G1B During HIV Infection (PREDIACC)

Study of the Role of PLA2G1B in the Immunopathogenicity by Action on CD4 T Cells During HIV Infection

The main objective of this study is to qualify and quantify, by microscopy techniques, CD4+ lymphocyte abnormalities during HIV infection in 7 patients who are naive to any ARV (antiretroviral ) treatment and secondarily to follow the kinetics of reversion of the observed abnormalities, as well as the evolution of the levels of PLA2G1B and its cofactor gp41 in 8 patients under ARV treatment

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Other: biological sample

Detailed Description

Antiretroviral therapy in HIV-infected patients has progressed significantly over the past two decades.

Viral replication in patients who are complicit in their treatment regimen is greatly reduced below detection limits (quantification) by current and approved laboratory tests. However, the persistence of residual (plasma) replication of the virus creates an inflammatory state associated with certain pathologies, accelerated aging and premature mortality. If treatment is discontinued for any reason, viral replication resumes within a few weeks in almost all patients.

Alternative infections of inflammatory pathways in HIV can also play a critical role in the inflammatory process suppressed by treatment. Members of the phospholipase A2 family can hydrolyze phospholipid molecules at the sn-2 position, making it a question about lipid moieties. One of the members, the phospholipase A2 group1B (PLA2G1B), is found in the plasma of HIV-infected patients who are not receiving antiretroviral therapy. Ex vivo, this enzyme is able to induce a purified CD4 lymphocyte energy from donors, as well as by inducing the lack of response to IL-7 (interleukin-7). In the long term, loss of response to IL-7 induces CD4 lymphopenia. Therefore, PLA2G1B must play an important role in the mechanism leading to HIV-infected patients becoming immunodeficient.

At the clinical level, we found that PLA2G1B activity increases in all HIV-infected patients and decreases after ARV treatment. On the other hand, for patients who are able to eliminate the HIV virus on therapy but whose immunological response remains low, PLA2G1B activity remains high. More interestingly, in "HIV Elite Controller" patients, PLA2G1B activity is not found in their plasma. Overall, there is a correlation between the different clinical groups (viremic not on therapy, ARV and virus removal with robust CD4+ T-cell response, virus removal with suboptimal CD4+ T-cell response and "HIV Elite Controller") and the activity level of PLA2G1B in their plasma.

The purpose of this study, more generally, is to study the role of PLA2G1B in CD4 lymphocytes and to analyze the reversion of its effects in the immunopathogenicity of HIV infection.

In the main study, 15 patients will be included. The analysis of the first 7 patients will in addition meet the objectives of the study, to determine the test that will allow the follow-up of the 8 other patients after ARV treatment. The participation of the 7 patients in the study is limited to 1 (one) day.

In the sub-study, the last 8 patients following their inclusion in the main study will enter a follow-up phase of 12 months after they are put on ARV treatment. The total duration of participation for the 8 patients will be 13 months.

The main study is carried out by taking 50 mL of total blood and in the sub-study, 30mL of blood sample will be taken during the follow-up visit (at M1, M3, M6, M9 and 12 Months) after ARV treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: THEZE; Phone Number: +33(0) 1 45 68 86 00; Email: jacques.theze@diaccurate.com
• Study Contact Backup: Name: DELIGNE; Phone Number: +33(0)1 44 38 93 93; Email: claire.deligne@diaccurate.com

Study Locations

• France
  • Paris, France, 75014
    • Recruiting
    • CIC 1417 Cochin Pasteur, hôpital Cochin
    • Contact: LAUNAY; Email: odile.launay@aphp.fr
    • Contact: KONATE; Phone Number: +33(0) 1 58 41 33 68; Email: eleine.konate@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant aged 18 to under 70
2. Participant having signed the written and informed consent;
3. Patient with HIV-1 infection documented by a positive HIV western blot positive (infected patients> 6 months, CD4 count> 350 / mm3 and HIV RNA <100.000 copies / mL) naive to any ARV treatment Anti-HIV antibody positive and an optical density <1.0, as determined by enzyme immunoassay, with no significant risk of clinical events
4. Appropriate laboratory data: hemoglobin> 9 g / dL, absolute neutrophil count ≥1000 / μL, platelets ≥50,000 / μL, bilirubin ≤ 1.5 X upper limit of normal (ULN) or ≤3 X ULN serum creatinine ≤ 1.5 X ULN, alanine amino transferase (ALT) or aspartate amino transferase (AST) ≤ 3 X ULN;
5. ECOG (Eastern Cooperative Oncology Group) performance status scale ≤2
6. Subject benefiting from a French social security scheme, or affiliated to such a scheme

Exclusion Criteria:

1. History of inflammatory disease such as rheumatoid arthritis, lupus, Crohn's disease, ulcerative colitis
2. Concomitant use of systemic or topical corticosteroids for the treatment of skin diseases. However, topical steroids and oral steroids (≤10 mg prednisone equivalent / day) are permitted if the patient has received a stable dose with stable symptoms for at least 4 weeks before inclusion in the study.
3. Major surgery <4 weeks before inclusion in the study.
4. A stem cell transplant.
5. History of other malignancies in the last three years except Kaposi controlled.
6. Infection known by hepatitis C or B virus (HCV or HBV)
7. Congestive heart failure, class III or IV, according to the criteria of the New York Heart Association (NYHA).
8. Vulnerable population (minors, pregnant, parturient or nursing women, persons under guardianship or trusteeship, or deprived of liberty by a judicial or administrative decision, under the protection of justice)
9. Patients with dementia or altered mental states who would not understand and provide an informed consent document

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: positive HIV patient not treated by ARV yet; Before starting HIV treatment, 15 patients will be included in the study and 50mL of whole blood will be taken. After treatment initiation 8 of the 15 patients will entered in the follow-up phase for 1 year (5 followup visit, M1, M3, M6, M9, M12) and 30mL of whole blood will be taken at each visit. The duration of the study for the 7 other patients will be 1 day.

Other: biological sample; whole blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
immunological : to qualify and quantify by confocal microscopic techniques and flow cytometry lymphocyte abnormalities	The assessment of the change in the proportion of lymphocytes at 1, 3, 6, 9 and 12 months as compared to Day 1: CD4 with membranes abnormalities above normal,; CD4 with major membrane abnormalities,; CD4 with signal transduction abnormalities,; CD4 reversing one of these abnormalities spontaneously or after treatment with neutralizing monoclonal antibody (mAb) 2B2	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
immunological	The assessment by immunophenotyping test ( flow cytometry) of the change at 1, 3, 6, 9 and 12 months as compared to Day 1 of: number of CD4/mm3 of blood, number of CD8/mm3 of blood, CD4 / CD8 ratio, viral load (copies of HIV RNA/mL of blood), viral DNA (copies of HIV DNA/mL of blood); number of CD4/mm3 secreting IFN gamma (Interferon gamma), TNF (Tumor necrosis factor) and IL-2 (Interleukin-2) (in % of IFN - TNFa - IL-2+ / CD4)	up to 1 year

Collaborators and Investigators

• Sponsor: Diaccurate SAS
• Collaborators: CIC 1417 Cochin-Pasteur
• Investigators: Principal Investigator: Odile LAUNAY, MD, PHD, CIC 1417 Clinical Center Investigation - Cochin Hospital, AP-HP

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2022

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: HIV infection; PLA2G1B; Lymphocyte CD4+
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: PREDIACC; 2018-A02025-50 (Registry Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No