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Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients (VIH-2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Collaborators:
Gilead Sciences
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01605890
First received: May 22, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

The HIV-2 is less common ie 1-2 million people in West Africa. HIV-2 does have the same sensibility to antiretroviral treatment (ART) compared to HIV-1. The ART strategies that are appropriate for the HIV-1 infection are not as effective for HIV-2. Classical triple therapy including PI is less effective for HIV-2. Also, the choice of ARTs in a second line treatment is limited. The first line optimal treatment has to be defined by a prospective and randomized evaluation of other strategies. The primary endpoint will be adapted to the specificity of the HIV-2 infection. The 1st step is to define, with a phase II clinical trial, whether a strategy including 2 NRTIs and raltegravir, as an alternative strategy to the classical triple therapy, shows an immunovirological response, at least, as good as the one obtained with the triple therapy. The hypothesis is that the low ART response observed in HIV-2 infection is due to a low virological strength of the ARTs used and that the combination of 2 NRTIs and raltegravir should show a therapeutic success of at least 50% at week 48.


Condition Intervention Phase
HIV-2 Infection
Drug: emtricitabine / tenofovir disoproxil fumarate / raltegravir .
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ANRS 159 VIH-2 : Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Proportion of participants in therapeutic success [ Time Frame: at Week 48 ] [ Designated as safety issue: Yes ]

    The participants will be considered in therapeutic success at Week 48 if they did not present any of the following events:

    • Plasma HIV-2 RNA load over or equal to 100 copies/mL, starting from Week 24 and confirmed within the next 4 weeks,
    • CD4 lymphocytes gain below 100/mm3 at Week 48 compared to the CD4 lymphocytes counts average between Week-4 and Week 0,
    • Raltegravir permanent discontinuation,
    • Death from any cause,
    • New B or C events confirmed by an endpoint review committee


Secondary Outcome Measures:
  • Gain in CD4 lymphocytes count [ Time Frame: between Week 0 and Week 12 ] [ Designated as safety issue: No ]
  • Tolerance of the treatment [ Time Frame: from Week 0 to Week 48 ] [ Designated as safety issue: Yes ]
    • number, nature, severity and time to adverse event.
    • evolution of the metabolic disorders, clinical and biological measurement

  • Evolution of the number and percentage of CD4 lymphocytes [ Time Frame: between Week 0 and Week 48 ] [ Designated as safety issue: Yes ]
  • Evolution of plasma HIV-2 RNA load [ Time Frame: between Week 0 and Week 48 ] [ Designated as safety issue: Yes ]
  • The rate of clinical progression will be defined as the switch [ Time Frame: from Week 0 to Week 48 ] [ Designated as safety issue: Yes ]
    • from category A to B, C or death.
    • from category B to C or death.

  • Adherence evaluated with ANRS self-administered questionnaire of adherence and plasma measurements of residual concentrations of antiretroviral drugs in viral failure cases [ Time Frame: from Week 0 to Week 48 ] [ Designated as safety issue: No ]
  • Description of the resistance mutations'profile in virological failure cases [ Time Frame: from Week 0 to Week 48 ] [ Designated as safety issue: Yes ]

    Description of the resistance mutations'profile in virological failure cases (plasma HIV-2 RNA load over or equal to 100 copies/mL after plasma HIV-2 RNA load below 100copies/mL, confirmed with a retest within the 4 following weeks) with:

    • the number and type of mutations in the RT and integrase genes compared to Week 0.
    • the evolution of the phenotypic sensitivity of raltegravir and NRTIs compared to Week 0

  • Frequency of treatment switch or discontinuation [ Time Frame: from Week 0 to Week 48 ] [ Designated as safety issue: No ]
    • overall (regardless of the molecule).
    • for each study drug (raltegravir and emtricitabine/tenofovir disoproxil fumarate combination).

  • Evolution of plasma HIV-2 DNA load in PBMC [ Time Frame: at Week 24 and Week 48 and compared to those performed at Week 0 ] [ Designated as safety issue: No ]
  • Evolution of the quality of life [ Time Frame: from Week 0 to Week 48 ] [ Designated as safety issue: No ]
    through PROQOL questionnaire


Estimated Enrollment: 35
Study Start Date: July 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: raltegravir / emtricitabine / tenofovir disoproxil fumarate Drug: emtricitabine / tenofovir disoproxil fumarate / raltegravir .

emtricitabine : 200 mg/day and tenofovir disoproxil fumarate : 300 mg/day, included in one pill of Truvada® QD.

raltegravir : 400 mg x 2/day, 400 mg in one pill of Isentress® BID.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age ≥18 years
  • HIV-2 mono infection, confirmed by ELISA and Western Blot test or Immunoblot,
  • antiretroviral treatment-naive, whatever the duration and indication of prior treatments,
  • indication to treatment, with at least one of the following criteria : type B or C events, CD4 lymphocytes count below 500/mm3 at screening-visit or CD4 lymphocytes count decrease of at least 50 cell/µL/year over the last 3 years with the last CD4 lymphocytes count within -/+ 10 % of the nadir, plasma HIV-2 RNA load over or equal to 100 copies/mL at screening-visit,
  • Pneumocystis prophylaxis if CD4 lymphocytes count below 200/mm3, combined to a toxoplasmosis prophylaxis in case of a positive toxoplasmosis serology,
  • French residency for at least one year,
  • Written informed consent, signed by the participant and the investigator (at the latest on the screening-visit and prior any study related intervention)
  • Affiliate or beneficiary of a social security system (State Medical Assistance is not a social security scheme).

Exclusion Criteria:

  • Absence of effective contraception method(women),
  • Pregnancy, breastfeeding or wish for pregnancy during the trial,
  • Curative treatment of a progressive opportunistic infection not compatible with those evaluated in the present study,
  • Malignant or tumorous affection requiring chemotherapy or radiotherapy,
  • Decompensated cirrhosis,
  • Viral hepatitis C with a Metavir score over F2,
  • Hemoglobinemia below 7g/dL, polynuclear neutrophils below 500/mm3, platelets below 50 000/mm3, creatinine clearance below 50 mL/mn, transaminase, alkaline phosphatase or bilirubin over 2.5N,
  • Contraindication to one of the excipients of study treatments,
  • Insuline-dependent diabetes mellitus not well controlled (with glycated haemoglobin (HbA1C) over 7%),
  • Long-term corticosteroid treatment (more than 3 weeks of treatment),
  • Judicial protection, legal guardianship,
  • Participation in other therapeutic trial or comprising an exclusion period ongoing at the time of the screening-visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605890

Contacts
Contact: Sophie Matheron, Pr +331 40 25 78 83 sophie.matheron@bch.aphp.fr

Locations
France
Inserm U897 Withdrawn
Bordeaux, France, 33076
Hôpital Bichat-Claude Bernard Recruiting
Paris, France, 75018
Contact: Sophie MATHERON, Pr    +33140257883      
Principal Investigator: Sophie Matheron, Pr         
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Gilead Sciences
Merck Sharp & Dohme Corp.
Investigators
Study Chair: Sophie Matheron, Pr Hopital Bichat-Claude Bernard
  More Information

No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT01605890     History of Changes
Other Study ID Numbers: 2011-005038-20, ANRS 159 VIH-2
Study First Received: May 22, 2012
Last Updated: June 23, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV-2

Additional relevant MeSH terms:
Emtricitabine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014