Evaluation of the Capacity of a Weekly Strategy of 4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV-1 Infected Patients With Undetectable Viral Load for at Least 12 Months, to Maintain a Virological Success With This Intermittent Maintenance Therapy After a Successful Continuous Induction Therapy.
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 100
- Locations
- 17
- Primary Endpoint
- Capacity to maintain a therapeutic success with 4 days on treatment followed 3 days off treatment
Study Overview
Brief Summary
Evaluate after 48 weeks, the capacity of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, in HIV-1 treated patients with undetectable viral load for at least 12 months and continuous antiretroviral regimen unchanged for at least 4 months, to maintain a therapeutic success defined by the absence of virological failure (2 consecutive viral loads > 50 cp/mL) and the absence of interruption of therapeutic strategy (interruption or change of the " 4 days on / 3 days off " strategy for a time longer than 30 consecutive days).
Detailed Description
Methods:
Open-label, multicentric, prospective, non-randomized, non-controlled trial to evaluate at 48 weeks, the capacity of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, in HIV-1 treated patients with undetectable viral load for at least 12 months and continuous antiretroviral regimen unchanged for at least 4 months, to maintain a therapeutic success defined by the absence of virological failure (2 consecutive viral loads > 50 cp/mL) and the absence of interruption of therapeutic strategy (interruption or change of the " 4 days on / 3 days off " strategy for a time longer than 30 consecutive days).
Allocation: Non-randomized Endpoint Classification: Safety/Efficacy Study Primary Purpose: Treatment
Enrollment: 100 patients
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •• HIV-1 documented infection
- •Age 18 years or older
- •HIV-1 viral load always ≤ 50 cp/mL for at least 12 months (with a minimum of 3 measures in the last 12 months, including screening)
- •CD4+ lymphocytes count > 250/mm3, for at least 6 months
- •Treatment with a stable regimen for at least 4 months prior to screening, containing 2 nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTI) combined with, either 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), or 1 ritonavir-boosted protease inhibitor (PI/r). The list of accepted antiretroviral drugs is limited to :
- •NRTI : tenofovir, emtricitabine, abacavir, lamivudine
- •PI/r : lopinavir/r, darunavir/r or atazanavir/r
- •NNRTI : efavirenz, rilpivirine or etravirine.
- •Exclusive antiretroviral 3 drug-therapy (no 4 drug-therapy)
- •A least one genotypic resistance test available (reverse transcriptase and/or protease amino acid sequence, according to on-going antiretroviral drugs) ; on each genotypic resistance test(s) available in medical history, susceptibility to every on-going antiretroviral drugs must be demonstrated
- •Clearance of the creatinine > 60 mL/min (MDRD)
- •ASAT and ALAT < 3 ULN
- •Hemoglobin > 10 g/dl
- •Platelets count > 100 000/mm3
- •Negative pregnancy test for potential child-bearing women and mechanical contraception for sexual intercourses
- •Patient living in France and affiliated to a social security system
- •Written informed consent
Exclusion Criteria
- •• HIV-2 infection
- •HBV infection (positive HBs antigen) or isolated positive HBc antibody
- •HCV infection requiring specific treatment during the 51 weeks of the trial
- •At least one known resistance to one of on-going antiretroviral drugs
- •Exclusive antiretroviral 3 drug-therapy (no 4 drug-therapy)
- •No genotypic resistance test available
- •On-going either interferon, interleukin treatment, or every immuno- / chemo-therapy
- •Progressive opportunistic infection, on-going treatment for opportunistic infection or tuberculosis
- •Patient with irregular follow-up or with treatment adherence problems
- •Any condition (alcohol, drug abuse...) compromising treatment adherence, treatment safety, and/or study adherence
- •Progressive neurological disorders (meningitis, encephalitis, myelitis...) related to HIV infection or not
- •Medical history of severe neuropsychiatric disorder, with insufficient treatment efficacy
- •Subject under legal guardianship or incapacitation
Arms & Interventions
Four consecutive days on treatment and 3 days off
All patients will take a combination of three HIV treatment with a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment
Intervention: Four consecutive days on treatment and 3 days off (Drug)
Outcomes
Primary Outcomes
Capacity to maintain a therapeutic success with 4 days on treatment followed 3 days off treatment
Time Frame: Week 48
To evaluate after 48 weeks, the capacity of a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment, in HIV-1 treated patients with undetectable viral load for at least 12 months and continuous antiretroviral regimen unchanged for at least 4 months, to maintain a therapeutic success defined by the absence of virological failure (2 consecutive viral loads \> 50 cp/mL) and the absence of interruption of therapeutic strategy (interruption or change of the " 4 days on / 3 days off " strategy for a time longer than 30 consecutive days).
Secondary Outcomes
- Evaluation CD4, CD8 and CD4/CD8 ratios(Week 0, week 8, week 16, week 24, week 24, week 32, week 40 and week 48)
- Virological success(Week 48)
- The blips(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- The low viral loads (between 20 - 50 cp/mL)(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- Detected signal on viral quantification(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- Mutations resistance(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- HIV proviral DNA(Week 0, Week 24 and Week 48)
- Clinical events related to HIV infection(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- Adverse events(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- Interruption or modification of the therapeutic strategy(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- Renal parameters(Week 0, week 8, week 16, week 24, week 32, week 40 and week 48)
- Inflammation and immune activation(Week 0, week 24 and Week 48)
- Antiretrovirals Pharmacokinetic(Week 0, week 24 and week 48)
- Antiretrovirals pharmacokinetic(week 4, week8, week 12, week 24, week 32 and week 48)
- The time of virological failure occurrence(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- Quality of life(week 0, week 24 and week 48)
- Adherence(Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51)
- Hepatitis parameters(Week 0, week 8, week 16, week 24, week 32, week 40 and week 48)
- Glucidolipidics parameters(Week 0, week 24 and week 48)