Efficacy of Adding Interleukin-2 to an Optimized Antiretroviral Regimen in HIV Patients in Therapeutic Failure (ANRS123)

Study of the Immunological Efficacy of Adding Subcutaneous Interleukin-2 (IL-2) to an Optimized Antiretroviral Regimen in HIV-1-infected Subjects Experiencing Therapeutic Failure on an Ongoing Antiretroviral Combination With a CD4 Cell Count ≤ 200/mm3 ANRS 123 Trial

Interleukin-2 (IL-2) increases the number of CD4 cells in HIV-1 infected patients with a CD4 cell count over 200/mm3, but its activity in patients with treatment failure and low CD4 cell counts is unknown. This study will test the efficacy and safety of IL-2 with an optimized antiretroviral regimen in patients with a CD4 count below 200/mm3 and a plasma viral load above 10,000 HIV RNA copies/ml.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Interleukin-2 (IL-2)

Detailed Description

IL-2 is produced naturally in the body and helps CD4 cells multiply. In earlier studies in HIV-infection, most of the patients with a controlled viral load and a high level of CD4 count (over 200/mm3) who received IL-2, experienced an increase of their CD4 cell count superior to what is observed with antiretroviral therapy alone.

The efficacy of IL-2 when the viral load is high and the CD4 cell count is low is not known. The purpose of this multicentric national study is to compare the effects of an optimized antiretroviral regimen with or without IL-2.The choice of the antiretroviral regimen will be made from a genotype resistance test.

Ninety eight HIV-1-infected patients experiencing advanced treatment failure with a CD4 count below 200/mm3 and a plasma viral load above 10,000 HIV RNA copies/ml, will be randomly assigned to one of two treatment groups: with or without IL-2.

The group with IL-2 will receive a dose of 4.5 million International units by subcutaneous injection twice a day for 5 days (up to a total of 8 cycles, ending at Week 42), the first two cycles 4 weeks apart, the following cycles 6 weeks apart.

Evaluation will be done at week 52 and further at W76. The primary endpoint is the proportion of patients reaching an absolute CD4 count over 200/mm3 at Week 52. Secondary endpoints include the proportion of patients increasing their CD4 count over 50/mm3 between Week 00 and Week 24,and between Week 00 and Week 52, the occurrence of HIV-related events, drug safety and the evolution of CD4 cells and of HIV RNA and HIV DNA loads over time.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Necker service des Maladies Infectieuses

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients with proven HIV-1-infection
• Prior or current exposition to at least 1 molecule from each of the 3 antiretroviral classes (NRTI, NNRTI and PI)
• In a situation of therapeutic failure on an ongoing regimen

Exclusion Criteria:

• Patients included in the Macrolin® expanded French access program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
proportion of patients reaching an absolute CD4 count over 200/mm3 at Week 52 (W52)

Secondary Outcome Measures

Outcome Measure
group B or C events (1993 CDC classification of HIV infection)between Week 00 and Week 96
median value of the CD4 count at W52
evolution of the CD4 count during the study
time to the first visit with a CD4 count ≥ 200/mm3
tolerance of IL-2
tolerance of antiretroviral drugs
evolution of the plasma HIV RNA load at W64 and W76
evolution of the HIV DNA level in PBMCs at W64 and W76
number of modifications of antiretroviral regimen until W52
clinical status at W64 and W76
CD4 count at W64, W76 and W96
plasma HIV RNA load at W64, W76 and W96
number of modifications of antiretroviral regimen at W64 and W76
proportion of patients increasing their CD4 count over 50/mm3 between Week 00 and Week 24, and between Week 00 and Week 52

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Collaborators: Chiron Corporation
• Investigators: Study Chair: Geneviève Chêne, Pr, INSERM unité 593; Principal Investigator: Jean Paul VIARD, Dr, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: June 7, 2005
• First Submitted That Met QC Criteria: June 7, 2005
• First Posted (Estimate): June 8, 2005

Study Record Updates

• Last Update Posted (Estimate): December 22, 2011
• Last Update Submitted That Met QC Criteria: December 21, 2011
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Treatment Experienced; Acquired Immunodeficiency Syndrome; Interleukin-2; Treatment failure
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Interleukin-2
• Other Study ID Numbers: 2004-001329-29; ANRS123