Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients (QUATUOR)

ANRS, Emerging Infectious Diseases

Status and phase: Unknown; Phase 3

Conditions: HIV Infections

Treatments: Drug: Treatment discontinuation

Study type: Interventional

Funder types: Other

Identifiers

NCT03256422

ANRS 170 - QUATUOR

Details and patient eligibility

About

The trial is an open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus continuous therapy, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral treatment since 4 months.

Full description

Open-label, multicenter, prospective, randomized trial in 2 parallel groups, evaluating at W48, the non-inferiority of antiretroviral treatment taken 4 consecutive days a week versus continuous therapy, in HIV infected patients with controlled viral load for at least 12 months and stable antiretroviral treatment since 4 months. The non-inferiority margin (delta) is 5%. The randomization will be stratified according to the family of the third antiretroviral agent (II, PI, and NNRTI). A minimum of 200 patients will be included in the integrase inhibitor strata to provide a sufficient power to assess the efficacy of strategy in this population.

At W48, all patients with virological success in the continuous therapy group will switch to the 4/7 days therapy.

Enrollment: 640 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• HIV-1 infection, coinfection HIV-1/HIV-2 possible
• Age≥18 years old
• Current therapy unchanged for the last 4 months
• Receiving tritherapy with 2 nucleoside reverse transcriptase inhibitor+protease inhibitors or 2 nucleoside reverse transcriptase inhibitor+non-nucleoside reverse transcriptase inhibitors or 2 nucleoside reverse transcriptase inhibitor+integrase inhibitors.

Allowed treatment drugs are :

1. nucleoside analogs : tenofovir (TDF ou TAF), emtricitabine, abacavir, lamivudine 2. protease inhibitors : lopinavir/r, darunavir/r ou atazanavir/r 3. Non nucleoside reverse transcriptase inhibitors : efavirenz, rilpivirine ou etravirine 4. integrase inhibitors : dolutegravir, elvitegravir/cobicistat ou raltegravir

• Viruses susceptible to all antiretroviral drugs present in the ongoing tritherapy (AC11-ANRS algorithm).

  1. If a genotype is available in the patient medical history; viruses must be susceptible to all ongoing antiretroviral drugs
  2. If no RNA genotype available, a genotype will be performed on DNA at screening and will not have to show any resistance to the ongoing antiretroviral drugs

• Viral load (VL) < 50 cp/mL in the past year, with at least 3 VL measurements including screening; only one episode of viral blip < 200 copies/mL is authorized in the last year

• CD4 T cells > 250/mm3 at the screening visit

• Estimated glomerular filtration rate > 60 mL/min (Chronic Kidney Disease - Epidemiology Collaboration method)

• Transaminases : aspartate aminotransférase et alanine aminotransférase < 3N

• Haemoglobin > 10 g/dL

• Platelets > 100 000/mm3

• For women of childbearing age, negative pregnancy test at screening; agree to use mechanical contraception during the study

• Social security system coverage

• Informed consent form signed by patient and investigator

Exclusion criteria

• Infection by HIV-2
• Chronic and active Viral B Hepatitis with positive antigen HBs
• Chronic and active Viral C Hepatitis with treatment expected in the next 98 weeks
• Concomitant treatment using interferon, interleukins, any other immune-therapy or chemotherapy, antivitaminK for patients on ARVT using a booster
• Concomitant prophylactic or curative treatment for an opportunistic infection
• All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with study protocol compliance, observance and/or study treatment tolerance
• Pregnant or breast feeding women
• Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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640 participants in 2 patient groups

4 days / 7

Experimental group

Description:

Patients included in this arm will take their ARV treatment 4 consecutive days per week during 98 weeks

Treatment:

Drug: Treatment discontinuation

7 days / 7

Active Comparator group

Description:

Patients included in this arm will continue their ARV therapy 7 days per weeks during 48 weeks and after W48, they will take their ARV treatment 4 days per week until W98

Treatment:

Drug: Treatment discontinuation