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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05482854
• Other study ID #: ANRS 175 RHIVIERA-01
• Status: Recruiting
• Phase: N/A
• Start date: March 20, 2023
• Est. completion date: July 2025

Study information

• Verified date: September 2023
• Source: ANRS, Emerging Infectious Diseases
• Contact: Vincent MEIFFREDY
• Phone: 00 33 1 45 59 52 06
• Email: vincent.meiffredy[@]inserm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: July 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ...).

Related Conditions & MeSH terms

• HIV Infections

Intervention

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

Locations

Country	Name	City	State
France	Centre Hospitalier du Pays d'Aix	Aix-en-Provence
France	Hôtel Dieu	Angers
France	Hôpital Avicenne	Bobigny
France	Hôpital PELLEGRIN	Bordeaux
France	Hôpital Saint-André	Bordeaux
France	Hôpital de la Côte de Nacre	Caen
France	Hôpital Gabriel Montpied	Clermont-Ferrand
France	Hôpital Le Bocage	Dijon
France	Hôpital Pierre Zobda-Quitman	Fort De France
France	Hôpital Raymond Poincaré	Garches
France	CHD Vendée	La Roche-sur-Yon
France	Hôpital de Bicêtre	Le Kremlin-Bicêtre
France	Hôpital de la Croix Rousse	Lyon
France	Hôpital Edouard HERRIOT	Lyon
France	Hôpital Sainte Marguerite	Marseille
France	Hôpital Gui de Chauliac	Montpellier
France	Hôtel Dieu	Nantes
France	Hôpital Carémeau	Nîmes
France	Hôpital de l'Hôtel-Dieu	Paris
France	Hôpital Lariboisière	Paris
France	Hôpital Saint-Louis	Paris
France	Hôpital Tenon	Paris
France	Hôtel Dieu	Paris
France	Institut Pasteur	Paris
France	La Pitié Salpêtrière	Paris
France	Hôpitaux Universitaires de Strasbourg	Strasbourg
France	Hôpital de Purpan	Toulouse
France	Hôpital Gustave Dron	Tourcoing
France	Hôpital Bretonneau	Tours
France	CHI Villeneuve Saint Georges	Villeneuve Saint Georges

Sponsors (1)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects with a Plasma HIV-1 RNA (viral load,VL) below 400 copies/mL at 6 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	The acceptation rate of the trial by eligible patients	Percentage of patients who accept to participate on patients pré-screened and eligible	At inclusion (Day 0)
Secondary	Proportion of patients with a plasma VL < 50 copies/ml at 3 and 6 months following Analytic Treatment Interruption (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
Secondary	Evolution of number of CD4 T cells count during ATI and after ART resumption	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)
Secondary	Evolution of CD4 to CD8 ratio during ATI and after ART resumption	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)
Secondary	Evolution of total and integrated HIV DNA and cell-associated HIV RNA transcripts	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)
Secondary	Evolution of HIV markers in sperm (on 25 participants)	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
Secondary	Evolution of the levels of inflammation markers during ATI	Physiological parameters levels will be studied (Luminex and Simoa technology): IFNa, TGFß, 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
Secondary	Proportion of patients who resumed treatment during the first 6 months of ATI, according to the reasons for resuming	Percentage of resumption, according to the reasons listed in the protocol, before the evaluation of the primary outcome	At week 24
Secondary	Pharmacological dosages of antiretrovirals performed during the ATI from frozen samples	Pharmacological dosages of antiretrovirals performed during the ATI at Week 2 and Week 24 of ATI	At Week 2 and Week 24 of ATI
Secondary	Proportion of patients reporting at each visit to use condoms	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).
Secondary	Proportion of patients reporting at each visit to have proposed PrEP at their partners	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).
Secondary	Proportion of patients satisfied with their participation at the end of the trial	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)
Secondary	Evolution of the level of the quality of life between inclusion and the end of the trial	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)
Secondary	Evolution of the global satisfaction with sexual life between inclusion and the end of the trial	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)