4 Consecutive Days on Treatment Followed by 3 Days Off Treatment, in HIV Patients

HIV-1 Infection Clinical Trial

— ANRS162-4D  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02157311
• Other study ID #: ANRS162-4D
• Secondary ID: 2014-000146-29
• Status: Completed
• Phase: Phase 3
• First received: May 21, 2014
• Last updated: January 26, 2016
• Start date: July 2014
• Est. completion date: January 2016

Study information

• Verified date: January 2016
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Four 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

Locations

Country	Name	City	State
France	Hôpital Avicenne	Bobigny
France	CHU Côte de Nacre	Caen
France	Centre Hospitalier Sud Francilien	Corbeil Essonnes
France	Hôpital Le Bocage	Dijon
France	Hôpital Meynard	Fort-de-france	Martinique
France	Hôpital Raymond Poincaré	Garches
France	Hôpital Bicêtre	Kremlin Bicetre
France	Hôpital Gui de Chauliac	Montpellier
France	Hôpital Bichat	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Necker	Paris
France	Hôpital Pitié-Salpêtrière	Paris
France	Hôpital Saint-Antoine	Paris
France	Hôpital Tenon	Paris
France	Hôpital Foch	Suresnes
France	Hôpital Purpan	Toulouse
France	Hôpital Bretonneau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Capacity to maintain a therapeutic success with 4 days on treatment followed 3 days off treatment	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).	Week 48	Yes
Secondary	Virological success	The HIV-1 viral load at week 48 must be inferior to 50 copies/mL	Week 48	Yes
Secondary	The time of virological failure occurrence	Measure the delay between week 0 and the date of the different virologic failure	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	The blips	Number of blips (viral load detectable on 1 sample) during the study	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	The low viral loads (between 20 - 50 cp/mL)	Measurement of the low viral loads (between 20 - 50 cop/mL)	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	Detected signal on viral quantification	The presence or not of detected signal when no quantification is possible on viral loads	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	Mutations resistance	The profile of new resistance mutations in case of virological failure	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	Evaluation CD4, CD8 and CD4/CD8 ratios	Measurement of the CD4 cell count, CD8 cell count, and CD4/CD8 ratio	Week 0, week 8, week 16, week 24, week 24, week 32, week 40 and week 48	No
Secondary	HIV proviral DNA	The evolution of HIV proviral DNA in the peripheral blood mononuclear cells (PBMC)	Week 0, Week 24 and Week 48	No
Secondary	Clinical events related to HIV infection	Clinical events related to HIV infection, according to the US CDC classification	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	Adverse events	Collect all clinical and biological adverse events	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	Interruption or modification of the therapeutic strategy	Every interruption or modification of the therapeutic strategy for more than 30 days	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	Yes
Secondary	Renal parameters	The evolution of creatinin and clearance of creatinin between week 0 and Week 48.	Week 0, week 8, week 16, week 24, week 32, week 40 and week 48	Yes
Secondary	Inflammation and immune activation	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	Week 0, week 24 and Week 48	No
Secondary	Antiretrovirals Pharmacokinetic	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	Week 0, week 24 and week 48	No
Secondary	Antiretrovirals pharmacokinetic	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	week 4, week8, week 12, week 24, week 32 and week 48	Yes
Secondary	Quality of life	selfquestionnary to measure the quality of life (PRO-QOL HIV and felt symptoms )	week 0, week 24 and week 48	No
Secondary	Adherence	Measurement of treatment adherence (questionnaire, self-survey book, pharmacological measures of antiretroviral drugs, medication event monitoring system)	Week 0, Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 51	No
Secondary	Hepatitis parameters	Measurment of AST, SGOT, CGT	Week 0, week 8, week 16, week 24, week 32, week 40 and week 48	No
Secondary	Glucidolipidics parameters	Measurement of Glycemia, Triglycerids, total cholesterol, HDL and LDL	Week 0, week 24 and week 48	No