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

ANRS, Emerging Infectious Diseases50 enrolled

Overview

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.

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

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 ...).

Outcomes

Primary Outcomes

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.

Time frame: Six months after treatment interruption (Week 24).

Secondary Outcomes

The acceptation rate of the trial by eligible patients

Percentage of patients who accept to participate on patients pré-screened and eligible

Time frame: At inclusion (Day 0)

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

Time frame: 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

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

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)

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

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)

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).

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)

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)

Time frame: 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

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

Time frame: 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

Percentage of resumption, according to the reasons listed in the protocol, before the evaluation of the primary outcome

Time frame: At week 24

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

Time frame: At Week 2 and Week 24 of ATI

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.

Time frame: 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

Document the emphasis being placed on the impact of access to information on prevention behaviors and the quality of sexual life.

Time frame: 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

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.

Time frame: 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

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.

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)

Evolution of the global satisfaction with sexual life between inclusion and the end of the trial