HIV-1 Infection
Conditions
Keywords
HIV-1, simplification,, treatment discontinuation, virological success, four days a week
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
Interventions
DRUGFour consecutive days on treatment and 3 days off
All patients will take a combination of three of these treatment with a weekly strategy of 4 consecutive days on treatment followed by 3 days off treatment
Sponsors
ANRS, Emerging Infectious Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 : 1. NRTI : tenofovir, emtricitabine, abacavir, lamivudine 2. PI/r : lopinavir/r, darunavir/r or atazanavir/r 3. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Measure the delay between week 0 and the date of the different virologic failure |
| 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 |
| Virological success | Week 48 | The HIV-1 viral load at week 48 must be inferior to 50 copies/mL |
| 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 biobank |
| Antiretrovirals 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 lab |
| 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 |
| 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 |
Countries
France
Outcome results
None listed