Phase II/III Study Evaluating the Effect of IL-2 on Preservation of the CD4 T-Lymphocytes After Interruption of Antiretroviral Treatment in HIV-Infected Patients With CD4 T-Lymphocyte Count Greater Than 500 Cells/mm3 Who Received Antiretroviral Tx
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Interleukin 2; HAART; Treatment interruption
Intervention description: Three cycles of IL-2 (6 MUI bid during 5 days = one cycle); HAART from week 0 to week 24; HAART is interrupted from week 24 in both arms
Intervention MeSH terms: Aldesleukin; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 148.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Interleukin 2; Treatment Interruption; HIV

Summary:

      This study will examine whether interleukin-2 (IL-2) given before the interruption of
      antiretroviral (ARV) treatment could significantly extend the period of time that a patient
      is temporarily not taking ARV treatment and also preserve CD4 counts above 350 cells per
      microliter. There will be an evaluation of the toxicity, or extremely harmful effects, of
      ARV, and the effect on quality of life.

      The use of ARV medications has greatly improved the condition and mortality of HIV-infected
      patients. But when used long term, those medications have been associated with great
      toxicities and medication fatigue. As a result, patients may not adhere to ARV use, and
      resistance to viruses may grow. The CD4 molecule is on the surface of helper T-lymphocytes,
      or T-helper cells. It serves as the primary receptor for HIV-1 and HIV-2, allowing the virus
      to gain entry into its host. The CD4 count increases immediately in response to ARV, giving
      an estimate of the state of a patient's immune system. Thus, it is a strong marker of the
      immediate risk of an opportunistic infection, one that takes advantage of a person's weakened
      immune system. IL-2 is a molecule naturally produced by activated T cells. In patients with
      HIV, IL-2 treatment can increase CD4 counts but the clinical importance of this increase is
      not clear. This study will compare the decline in CD4 count, when ARV is interrupted, in two
      random groups of participants: (1) those who will receive three cycles of IL-2 (one every 8
      weeks) in combination with ARV therapy for the first 24 weeks of the study before stopping
      ARV and (2) those who will receive ARV therapy without IL-2 for 24 weeks before stopping ARV.

      Patients 18 years of age or older who have HIV-1 infection and who have been on ARV therapy
      for at least 1 year, and who currently have a CD4 count 500 cells per microliter or higher
      and never had a CD4 count of less than 200 cells per microliter and a viral load less than
      the limit of detection, may be eligible for this study.

      Participants will undergo the following procedures and tests:

        -  Physical examination.

        -  Blood tests to measure blood lipids (fats), sugar, complete blood count including
           platelets, and chemistries.

        -  Assessment of fat distribution.

        -  Questionnaire about quality of life.

      In addition, those participants who are randomly placed in the group receiving IL-2 and ARV
      will get an echocardiogram at the beginning of the study and at week 24. They will receive a
      starting dose of 6 million units of IL-2 as an injection under the skin twice a day. Each of
      the three IL-2 cycles will last 5 days. After the 24-week period, participants in both groups
      will stop taking ARV medications if their CD4 count is still equal to or greater than 500
      cells per microliter. The study will continue into 120 weeks. Participants will be asked to
      continue to visit the clinic every 8 weeks for evaluation of their viral load and CD4 counts.
      Every 24 weeks, they will be asked to answer a questionnaire about their quality of life.
      Blood tests and other measurements will also be done as follow-up.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Age greater than or equal to 18 years.

        HIV-1 infection confirmed by ELISA and Western Blot before screening.

        Category A or B HIV-1 infection.

        Antiretroviral treatment:

          -  started at least 12 months prior to screening visit;

          -  stable and continuous for at least 12 weeks prior to screening visit;

          -  modified no more than once for virologic failure.

        IL-2 naive

        CD-4(+) T-lymphocyte count greater than or equal to 500 cells/mm(3) in the twelve weeks
        prior to screening (historical) and at screening.

        Nadir CD4(+) T-lymphocyte count greater than or equal to 200 cells/mm(3) prior to screening
        visit (that is, no measurement whose values may be less than 200/mm(3) since diagnosis of
        the HIV infection.

        Plasma HIV RNA less than 50 copies/ml in the 12 weeks preceding screening (historical, less
        than limit of detection if different method and/or cut off used) and at screening.

        For women of child-bearing age: use of effective contraception (hormonal such as birth
        control pill or injections, intrauterine device, surgical sterilization and/or mechanical
        barrier methods such as diaphragm or condoms); for all participants agreement to fully
        comply with prevention of transmission recommendations during periods of viremia if
        sexually active (latex condoms with or without additional barrier methods).

        Desire to interrupt antiretroviral therapy.

        Ability to sign informed consent (no later than W-2).

        EXCLUSION CRITERIA:

        Previous treatment with IL-2.

        Combined treatment with interferon, other interleukins, anti-HIV vaccines, systemic (not
        topical or inhaled) corticosteroids and hydroxyurea within the previous 12 weeks.

        Diagnosis of AIDS.

        Acute infection in the 14 days preceding inclusion.

        Pregnant, lactating woman desiring conception or not using contraception.

        Hemoglobin less than 10 g/dl; neutrophils less than 1,000/mm(3); platelets less than
        50,000/mm(3); creatinine greater than 1.5 times the upper limit of normal (N); bilirubin
        greater than 3N; AST or ALT greater than 3 N.

        Progressive disease of malignant, psychiatric, cardiac, pulmonary, thyroid, renal or
        neurological (peripheral or central) origin or severe disorders of hemostasis.

        Severe uncontrolled hypertension.

        Previous or progressive pathology contraindicating the administration of IL-2.

        History of extensive psoriasis, Crohn's disease or auto-immune disease involving severe
        complications.

        HTLV-1 infection (ELISA positive).

        Hepatitis B virus co-infection treated with lamivudine or tenofovir or adefovir.

        Since atazanavir use can be associated with higher bilirubin levels (mostly indirect) in
        the absence of clinical consequences, subjects on atazanavir with bilirubin up to 4.5 times
        N may be allowed to participate if the levels have been stable and after approval by the PI
        or the PI designated covering physician.