Clinical trial NCT05482854: Assessment of HIV Remission Upon cART Interruption in Early Treated Individuals Carrying the MHC B35/53Bw4TTC2 Genotype
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: HIV Infections
Keywords: treatment interruption
HIV remission
Post-treatment control
HLA-B35
Early treatment
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2022-08-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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).
Primary purpose: OTHER

Brief 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.

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.

Eligibility criteria: 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 ...).

Primary outcomes:
measure: Proportion of subjects with a Plasma HIV-1 RNA (viral load,VL) below 400 copies/mL at 6 months after Treatment interruption (Week 24).
timeFrame: Six months after treatment interruption (Week 24).
Secondary outcomes:
measure: The acceptation rate of the trial by eligible patients
timeFrame: At inclusion (Day 0)
measure: Proportion of patients with a plasma VL < 50 copies/ml at 3 and 6 months following Analytic Treatment Interruption (ATI)
timeFrame: At 3 months (week 12) and 6 months (week 24) following ATI
measure: Evolution of number of CD4 T cells count during ATI and after ART resumption
timeFrame: During all ATI period (from Day 0 to Day 0 ART resumption - maximum 48 weeks) and during ART resumption period (maximum 24 Weeks)
measure: Evolution of CD4 to CD8 ratio during ATI and after ART resumption
timeFrame: During all ATI period (from Day 0 to Day 0 ART resumption - maximum 48 weeks) and during ART resumption period (maximum 24 Weeks)
measure: Evolution of total and integrated HIV DNA and cell-associated HIV RNA transcripts
timeFrame: 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)
measure: Evolution of HIV markers in sperm (on 25 participants)
timeFrame: During ATI period (At Day 0, Week 4, Week 12, Week 24) and at Day 0 ART resumption
measure: Evolution of the levels of inflammation markers during ATI
timeFrame: During ATI period (up to week 24 ATI) and at Day 0 ART resumption
measure: Proportion of patients who resumed treatment during the first 6 months of ATI, according to the reasons for resuming
timeFrame: At week 24
measure: Pharmacological dosages of antiretrovirals performed during the ATI from frozen samples
timeFrame: At Week 2 and Week 24 of ATI
measure: Proportion of patients reporting at each visit to use condoms
timeFrame: From date of inclusion to the last follow-up visit, up to 72 weeks (average of 1 year).
measure: Proportion of patients reporting at each visit to have proposed PrEP at their partners
timeFrame: From date of inclusion to the last follow-up visit, up to 72 weeks (average of 1 year).
measure: Proportion of patients satisfied with their participation at the end of the trial
timeFrame: Questionnaire at the end of the study (Week 48 ou Week 24 resumption). Questionnaire at screening (in case of refusal to participate)
measure: Evolution of the level of the quality of life between inclusion and the end of the trial
timeFrame: 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)
measure: Evolution of the global satisfaction with sexual life between inclusion and the end of the trial
timeFrame: 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)
Other outcomes:
Locations:
city: Aix-en-Provence
country: France
facility: Centre Hospitalier du Pays d'Aix
city: Angers
country: France
facility: Hôtel Dieu
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Hôpital Saint-André
city: Bordeaux
country: France
facility: Hôpital PELLEGRIN
city: Caen
country: France
facility: Hôpital de la Côte de Nacre
city: Clermont-Ferrand
country: France
facility: Hôpital Gabriel Montpied
city: Dijon
country: France
facility: Hôpital Le Bocage
city: Fort De France
country: France
facility: Hôpital Pierre Zobda-Quitman
city: Garches
country: France
facility: Hôpital Raymond Poincaré
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital de Bicêtre
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Lyon
country: France
facility: Hôpital Edouard HERRIOT
city: Marseille
country: France
facility: Hôpital Sainte Marguerite
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
city: Nantes
country: France
facility: Hôtel Dieu
city: Nîmes
country: France
facility: Hôpital Carémeau
city: Paris
country: France
facility: Hôtel Dieu
city: Paris
country: France
facility: La Pitié Salpêtrière
city: Paris
country: France
facility: Institut Pasteur
city: Paris
country: France
facility: Hôpital de l'Hôtel-Dieu
city: Paris
country: France
facility: Hôpital Lariboisière
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: Hôpital de Purpan
city: Tourcoing
country: France
facility: Hôpital Gustave Dron
city: Tours
country: France
facility: Hôpital Bretonneau
city: Villeneuve Saint Georges
country: France
facility: CHI Villeneuve Saint Georges
Study officials:
affiliation: Hôpital Bicêtre, Service de médecine interne et d'immunologie clinique
name: Cécile GOUJARD
role: PRINCIPAL_INVESTIGATOR
References: