Assessment of HIV Remission Upon cART Interruption in Early Treated Individuals Carrying the MHC B35/53Bw4TTC2 Genotype

September 28, 2023 updated by: ANRS, Emerging Infectious Diseases

ANRS 175 RHIVIERA-01: Assessment of HIV Remission Upon Combination Antiretroviral Therapy (cART) Interruption in Early Treated Individuals From ANRS CO6 PRIMO Cohort Carrying the Major Histocompatibility Complex (MHC) B35/53Bw4TTC2 Genotype

The aim of the trial is to evaluate in ANRS CO6 PRIMO cohort participants if the presence of the MHC B35 (53) Bw4TTC2 genotype favors the control of HIV infection (defined by a viral load (VL) less than 400 cp/mL) after discontinuation of antiretroviral therapy (ART) initiated during primary HIV infection.

The trial will be a pilot "proof of concept", one arm, multicenter, nested in the ANRS CO6 PRIMO Cohort, in which the intervention is treatment interruption (of at least 6 months).

It is planned to include between 20 and 50 participants.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The ANRS 175 RHIVIERA 01 trial will focus on people who were initiated early and have a particular genotypic profile associated with HIV remission.

The study proposes to test an intervention consisting in a ART-treatment interruption (of at least 6 months) in ANRS CO6 PRIMO cohort participants carrying the MHC B35/53Bw4TTC2 genotype and well controlled on cART.

The study aims to enrol 20-30 participants in 30 French clinical sites. Participants will be enrolled after checking eligibility criteria and will interrupt ART immediatly after inclusion.

Control of HIV-Infection, defined by a viral load less than 400 cp/mL, will be evaluated after 24 weeks of interruption.

Study duration will vary by participant, depending on the time of ART interruption and the time to viral rebound. Participants will be followed maximum 48 weeks on ATI. If there is a viral rebound justifying the resumption of ART, participant will be followed 24 weeks maximum after resumption. The maximum duration of the study will be 48+24 = 72 weeks.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Aix-en-Provence, France, 13616
        • Recruiting
        • Centre Hospitalier du Pays d'Aix
        • Principal Investigator:
          • Thierry ALLEGRE, MD
        • Contact:
      • Angers, France, 49033
        • Withdrawn
        • Hotel Dieu
      • Bobigny, France, 93000
        • Active, not recruiting
        • Hôpital Avicenne
      • Bordeaux, France, 33075
        • Active, not recruiting
        • Hôpital Saint-André
      • Bordeaux, France, 33076
        • Withdrawn
        • Hôpital Pellegrin
      • Caen, France, 14033
        • Withdrawn
        • Hôpital de la Côte de Nacre
      • Clermont-Ferrand, France, 63000
        • Active, not recruiting
        • Hopital Gabriel Montpied
      • Dijon, France, 21034
      • Fort De France, France, 97261
        • Active, not recruiting
        • Hôpital Pierre Zobda-Quitman
      • Garches, France, 92380
        • Recruiting
        • Hopital Raymond Poincare
        • Contact:
        • Principal Investigator:
          • Pierre DE TRUCHIS, MD
      • La Roche-sur-Yon, France, 85925
        • Withdrawn
        • CHD Vendee
      • Le Kremlin-Bicêtre, France, 94275
        • Active, not recruiting
        • Hopital de Bicetre
      • Lyon, France, 69317
        • Withdrawn
        • Hopital de la croix rousse
      • Lyon, France, 69437
        • Active, not recruiting
        • Hopital Edouard Herriot
      • Marseille, France, 13274
        • Active, not recruiting
        • Hôpital Sainte Marguerite
      • Montpellier, France, 34295
        • Active, not recruiting
        • Hopital Gui de Chauliac
      • Nantes, France, 44035
      • Nîmes, France, 30029
      • Paris, France, 75475
        • Recruiting
        • Hopital Saint-Louis
        • Contact:
        • Principal Investigator:
          • Jean-Michel MOLINA, PhD
      • Paris, France, 75004
        • Withdrawn
        • Hotel Dieu
      • Paris, France, 75013
        • Withdrawn
        • La Pitié Salpêtrière
      • Paris, France, 75015
        • Withdrawn
        • Institut Pasteur
      • Paris, France, 75181
        • Recruiting
        • Hôpital de l'Hôtel-Dieu
        • Contact:
        • Principal Investigator:
          • Jean-Paul VIARD, PhD
      • Paris, France, 75475
        • Withdrawn
        • Hopital Lariboisiere
      • Paris, France, 75970
        • Withdrawn
        • Hôpital Tenon
      • Strasbourg, France, 67091
        • Active, not recruiting
        • Hôpitaux Universitaires de Strasbourg
      • Toulouse, France, 31059
      • Tourcoing, France, 59027
        • Recruiting
        • Hôpital Gustave Dron
        • Contact:
        • Principal Investigator:
          • Olivier ROBINEAU, PhD
      • Tours, France, 37044
        • Active, not recruiting
        • Hopital Bretonneau
      • Villeneuve Saint Georges, France, 94195
        • Active, not recruiting
        • CHI Villeneuve Saint Georges

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18 years at the time of consent
  • Enrolled and currently followed in a site of the ANRS CO6 PRIMO Cohort
  • With the MHC genotype: at least one HLA B35 or B53 allele AND one HLA-A or B allele carrying the Bw4 epitope AND homozygous -21T residue in the HLA-B alleles AND heterozygous or homozygous for C2 epitope-carrying HLA-C alleles
  • Treated with cART within 3 months following inclusion in ANRS CO6 Primo Cohort during at least 18 months and cART not modified in the last 3 months
  • Controlled on cART: > 90% of VL below 50 cp/mL after initial virological response
  • All VL below 50 cp/mL during the previous 12 months
  • Most recent CD4 measurement on cART above 500 cells/mm3
  • Written and informed consent signed by the person and the investigator (no later than the day of pre-inclusion and prior to any examination realized in the frame of the study (article L1122-1-1 of the Public Health Code)
  • Person affiliated or beneficiary of a social security scheme (article L1121-11 of the Public Health Code) (State Medical Aid or AME is not a social security scheme)
  • Patient agreeing to participate in the trial according to the defined procedures.

Exclusion Criteria:

  • One VL above 1000 cp/mL on or off antitretrovirals after the initial viral control on antiretrovirals was achieved.
  • Patient on long-acting injectable HIV treatment
  • Patient in whom condom sex use or PrEP use by the partner will be difficult or impossible.
  • Woman with a pregnancy project and pregnant woman.
  • Patient under guardianship or curatorship.
  • History of a clinical AIDS event or cancer.
  • Active HCV or HBV infection.
  • Any symptoms or laboratory values suggesting a systemic disorder (renal, hepatic, cardiovascular, pulmonary) or other medical conditions, related to HIV or not, which contraindicates the interruption of ARVs.
  • Recent SARS-CoV-2 infection and / or associated with a drop in CD4 and / or associated with a resumption of CV in the last 6 months. In this situation, wait until the CD4 has returned to a rate > 500/mm3 and a CV < 50 copies / mL consolidated for > 6 months.
  • Affection, disability, resulting from a SARS-CoV-2 infection, regardless of the duration of the SARS-CoV-2 infection.
  • Patient participating in another research evaluating other treatments with an exclusion period ongoing at the screening visit.
  • Planned absence which could prevent optimal trial participation (vacation abroad, moving, imminent job change ...).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients treated early and carrying the MHC B35/53Bw4TTC2 Genotype
Patients included in the ANRS CO6 PRIMO cohort, treated early and carrying the MHC B35/53Bw4TTC2 Genotype
Other: Analytical Treatment Interruption (ATI)

Analytical Interruption of Treatment for 24-48 weeks

ART resumption and follow-up for 24 weeks if the participant meets at least one ART resumption criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of subjects with a Plasma HIV-1 RNA (viral load,VL) below 400 copies/mL at 6 months after Treatment interruption (Week 24).
Time Frame: Six months after treatment interruption (Week 24).
Proportion of subjects with a Plasma HIV-1 RNA below 400 copies/mL on subjects included at 6 months after Treatment interruption.
Six months after treatment interruption (Week 24).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The acceptation rate of the trial by eligible patients
Time Frame: At inclusion (Day 0)
Percentage of patients who accept to participate on patients pré-screened and eligible
At inclusion (Day 0)
Proportion of patients with a plasma VL < 50 copies/ml at 3 and 6 months following Analytic Treatment Interruption (ATI)
Time Frame: At 3 months (week 12) and 6 months (week 24) following ATI
Proportion of patients with a plasma VL < 50 copies/ml at 3 and 6 months following ATI
At 3 months (week 12) and 6 months (week 24) following ATI
Evolution of number of CD4 T cells count during ATI and after ART resumption
Time Frame: During all ATI period (from Day 0 to Day 0 ART resumption - maximum 48 weeks) and during ART resumption period (maximum 24 Weeks)
Measurement of CD4 T cells count at Screening, Day 0, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, Week 24, Week 36, Week 48, Day 0 ART resumption, Week 4 resumption, Week 12 resumption, Week 24 resumption
During all ATI period (from Day 0 to Day 0 ART resumption - maximum 48 weeks) and during ART resumption period (maximum 24 Weeks)
Evolution of CD4 to CD8 ratio during ATI and after ART resumption
Time Frame: During all ATI period (from Day 0 to Day 0 ART resumption - maximum 48 weeks) and during ART resumption period (maximum 24 Weeks)
Measurement of CD4 to CD8 at Screening, Day 0, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, Week 24, Week 36, Week 48, Day 0 ART resumption, Week 4 resumption, Week 12 resumption, Week 24 resumption
During all ATI period (from Day 0 to Day 0 ART resumption - maximum 48 weeks) and during ART resumption period (maximum 24 Weeks)
Evolution of total and integrated HIV DNA and cell-associated HIV RNA transcripts
Time Frame: During ATI period (At Day 0, Week 4, Week 12, Week 24) and during ART resumption period (at Day 0 Resumption, and Week 24 ART Resumption)
Quantification of total HIV-DNA and integrated HIV-DNA by ultrasensitive techniques (ultrasensitive real-time PCR and Alu PCR) Quantification of intracellular HIV-RNA transcripts by ultrasensitive technique (ultrasensitive qPCR gag).
During ATI period (At Day 0, Week 4, Week 12, Week 24) and during ART resumption period (at Day 0 Resumption, and Week 24 ART Resumption)
Evolution of HIV markers in sperm (on 25 participants)
Time Frame: During ATI period (At Day 0, Week 4, Week 12, Week 24) and at Day 0 ART resumption
Quantification of HIV DNA on semen cells (ultrasensitive technique) and quantification of HIV RNA on seminal fluid (ultrasensitive technique)
During ATI period (At Day 0, Week 4, Week 12, Week 24) and at Day 0 ART resumption
Evolution of the levels of inflammation markers during ATI
Time Frame: During ATI period (up to week 24 ATI) and at Day 0 ART resumption
Physiological parameters levels will be studied (Luminex and Simoa technology): IFNα, TGFβ, IL-7, IL-12, IL-15, IL-18, IP-10, DPPIV, ARNr 16S, I-FABP, citrulline, sCD14, sCD163
During ATI period (up to week 24 ATI) and at Day 0 ART resumption
Proportion of patients who resumed treatment during the first 6 months of ATI, according to the reasons for resuming
Time Frame: At week 24
Percentage of resumption, according to the reasons listed in the protocol, before the evaluation of the primary outcome
At week 24
Pharmacological dosages of antiretrovirals performed during the ATI from frozen samples
Time Frame: At Week 2 and Week 24 of ATI
Pharmacological dosages of antiretrovirals performed during the ATI at Week 2 and Week 24 of ATI
At Week 2 and Week 24 of ATI
Proportion of patients reporting at each visit to use condoms
Time Frame: From date of inclusion to the last follow-up visit, up to 72 weeks (average of 1 year).
Document the emphasis being placed on the impact of access to information on prevention behaviors and the quality of sexual life.
From date of inclusion to the last follow-up visit, up to 72 weeks (average of 1 year).
Proportion of patients reporting at each visit to have proposed PrEP at their partners
Time Frame: From date of inclusion to the last follow-up visit, up to 72 weeks (average of 1 year).
Document the emphasis being placed on the impact of access to information on prevention behaviors and the quality of sexual life.
From date of inclusion to the last follow-up visit, up to 72 weeks (average of 1 year).
Proportion of patients satisfied with their participation at the end of the trial
Time Frame: Questionnaire at the end of the study (Week 48 ou Week 24 resumption). Questionnaire at screening (in case of refusal to participate)

Through statistical analyses of some self-administered questionnaires items (Likert).

On a Likert scale, a person selects one option among several that reflects how much they agree with a statement. The scale generally consists of five or seven balanced responses that people can choose from.
Questionnaire at the end of the study (Week 48 ou Week 24 resumption). Questionnaire at screening (in case of refusal to participate)
Evolution of the level of the quality of life between inclusion and the end of the trial
Time Frame: Questionnaire at Day 0, at Week 24 (or resumption of ART) and at the end of the study (Week 48 ou Week 24 resumption). Questionnaire at screening (in case of refusal to participate)
Through statistical analyses of some self-administered questionnaires items ( SF12.v2 scale for quality of life). The 12-item Short-Form Health Survey is a widely used, generic patient-reported measure of health status that provides summary scores of physical and mental health. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.
Questionnaire at Day 0, at Week 24 (or resumption of ART) and at the end of the study (Week 48 ou Week 24 resumption). Questionnaire at screening (in case of refusal to participate)
Evolution of the global satisfaction with sexual life between inclusion and the end of the trial
Time Frame: Questionnaire at Day 0, at Week 24 (or resumption of ART) and at the end of the study (Week 48 ou Week 24 resumption). Questionnaire at screening (in case of refusal to participate)

Through statistical analyses of some self-administered questionnaires items (Likert).

On a Likert scale, a person selects one option among several that reflects how much they agree with a statement. The scale generally consists of five or seven balanced responses that people can choose from.
Questionnaire at Day 0, at Week 24 (or resumption of ART) and at the end of the study (Week 48 ou Week 24 resumption). Questionnaire at screening (in case of refusal to participate)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANRS, Emerging Infectious Diseases

Investigators

  • Principal Investigator: Cécile GOUJARD, Hôpital Bicêtre, Service de médecine interne et d'immunologie clinique

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2023

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

January 3, 2022

First Submitted That Met QC Criteria

July 28, 2022

First Posted (Actual)

August 1, 2022

Study Record Updates

Last Update Posted (Actual)

September 29, 2023

Last Update Submitted That Met QC Criteria

September 28, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 175 RHIVIERA-01

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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