4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV Patients
- Conditions
- HIV-1 Infection
- Interventions
- Drug: Four consecutive days on treatment and 3 days off
- Registration Number
- NCT02157311
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
-
• 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
-
-
• 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Four consecutive days on treatment and 3 days off 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
- Primary Outcome Measures
Name Time Method Capacity to maintain a therapeutic success with 4 days on treatment followed 3 days off treatment 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 Outcome Measures
Name Time Method Virological success Week 48 The HIV-1 viral load at week 48 must be inferior to 50 copies/mL
The blips Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 Number of blips (viral load detectable on 1 sample) during the study
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 Measurement of the low viral loads (between 20 - 50 cop/mL)
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 The presence or not of detected signal when no quantification is possible on viral loads
Mutations resistance Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 The profile of new resistance mutations in case of virological failure
Evaluation CD4, CD8 and CD4/CD8 ratios Week 0, week 8, week 16, week 24, week 24, week 32, week 40 and week 48 Measurement of the CD4 cell count, CD8 cell count, and CD4/CD8 ratio
HIV proviral DNA Week 0, Week 24 and Week 48 The evolution of HIV proviral DNA in the peripheral blood mononuclear cells (PBMC)
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 Clinical events related to HIV infection, according to the US CDC classification
Adverse events Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 Collect all clinical and biological adverse events
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 Every interruption or modification of the therapeutic strategy for more than 30 days
Renal parameters Week 0, week 8, week 16, week 24, week 32, week 40 and week 48 The evolution of creatinin and clearance of creatinin between week 0 and Week 48.
Inflammation and immune activation Week 0, week 24 and Week 48 The evolution of inflammation and immune activation parameters (IL-6, CRP-US, CD14s, IP-10 and MIG-1).
The measurement will be done at the end of the study in a central lab on the biobankAntiretrovirals Pharmacokinetic Week 0, week 24 and week 48 The evolution of pharmacokinetic parameters, for protease inhibitors (lopinavir, darunavir or atazanavir) or non-nucleoside reverse transcriptase inhibitors (efavirensz, etravirine or rilpivirine) The measurment will be done on the sample bank at the end of the study in a central lab
Antiretrovirals pharmacokinetic week 4, week8, week 12, week 24, week 32 and week 48 Measurment of Residual plasmatic concentrations of protease inhibitors (lopinavir/r - darunavir/r - atazanavir/r ) or non-nucleoside reverse transcriptase inhibitors (efavirenz or rilpivirine or etravirine), at the end of the 3-days off, from Day 0 to week 48.
The measurment will be done on the sample bank at the end of the study in a central labThe 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 Measure the delay between week 0 and the date of the different virologic failure
Quality of life week 0, week 24 and week 48 selfquestionnary to measure the quality of life (PRO-QOL HIV and felt symptoms )
Adherence Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51 Measurement of treatment adherence (questionnaire, self-survey book, pharmacological measures of antiretroviral drugs, medication event monitoring system)
Hepatitis parameters Week 0, week 8, week 16, week 24, week 32, week 40 and week 48 Measurment of AST, SGOT, CGT
Glucidolipidics parameters Week 0, week 24 and week 48 Measurement of Glycemia, Triglycerids, total cholesterol, HDL and LDL
Trial Locations
- Locations (17)
Centre Hospitalier Sud Francilien
🇫🇷Corbeil Essonnes, France
Hôpital Meynard
🇫🇷Fort-de-france, Martinique, France
Hôpital Gui de Chauliac
🇫🇷Montpellier, France
Hôpital Bicêtre
🇫🇷Kremlin Bicetre, France
Hôpital Avicenne
🇫🇷Bobigny, France
CHU Côte de Nacre
🇫🇷Caen, France
Hôpital Saint-Antoine
🇫🇷Paris, France
Hôpital Raymond Poincaré
🇫🇷Garches, France
Hôpital Bichat
🇫🇷Paris, France
Hôpital Pitié-Salpêtrière
🇫🇷Paris, France
Hôpital Tenon
🇫🇷Paris, France
Hôpital Foch
🇫🇷Suresnes, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Hôpital Bretonneau
🇫🇷Tours, France
Hôpital Purpan
🇫🇷Toulouse, France
Hôpital Necker
🇫🇷Paris, France
Hôpital Le Bocage
🇫🇷Dijon, France