Protocol Number: 05-I-0123

Title:

A Randomized, Open-Label, International Study of Subcutaneous Recombinant Interleukin-2 (rIL-2, Aldesleukin) with and without Concomitant Antiretroviral Therapy in Participants w/HIV-1 Infection and CD4+ Cell Counts Greater Than or Equal to 300/mm(3)

Number:

05-I-0123

Summary:

This study will determine the safety and side effects of interleukin-2 (IL-2) taken with or without anti-HIV drugs and will see if IL-2 with or without anti-HIV drugs causes an increase in CD4 cells or a change in HIV viral load compared with no therapy at all. IL-2 is a protein that is produced naturally in the body and helps boost production of infection-fighting CD4 cells.

HIV-infected patients 18 years of age and older who have not previously taken IL-2 or taken any anti-HIV drug within 1 year of entering this study may be eligible for the study. Candidates are screened with a physical examination and blood tests during at least two screening clinic visits.

Participants are assigned by chance to one of the following three treatment groups:

-Standard of care treatment: This group does not receive IL-2 or anti-HIV drugs.

-IL-2 alone: This group receives three treatment cycles of IL-2. A cycle consists of an injection of IL-2 under the skin twice a day for 5 days in a row, followed by 7 weeks of no IL-2. After three cycles, patients may continue additional cycles for up to 2 years if the therapy is believed to be helpful. Patients are taught how to self-administer the IL-2.

-IL-2 plus anti-HIV drugs around IL-2 cycles only: This group receives three cycles of IL-2 as outlines above, but also receives 10 days of anti-HIV drugs around the IL-2 cycles (3 days before, 5 days during, and 2 days after IL-2 cycles).

Patients in the first two groups may begin anti-HIV therapy at any time they or their doctors believe it would be in their best interest to do so, and patients in the third group may begin continuous anti-HIV therapy or, conversely, stop all anti-HIV drugs, at any time it is believed to be in their best interest to do so.

All patients are followed in the clinic at least once a month for 8 months and then at least every 4 months for up to 2 years. The follow-up includes blood tests and possibly a visit with a doctor or nurse. Patients who develop side effects may need to be seen more frequently and may require additional blood and urine tests. Patients receiving IL-2 are seen for a clinical examination or blood tests, or both, to ensure that they are well before receiving each cycle. They are also seen on the last day of the dosing cycle and once again about one month after each cycle. They may need to be seen more often if they have a history of serious side effects during prior IL-2 treatments or if they develop serious side effects. Women who can become pregnant have a pregnancy test before starting each IL-2 cycle.

Some of the blood drawn for this study is used for genetic tests, and some blood is collected and stored for future studies.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Documented HIV-1 infection by any licensed ELISA test and confirmed by a second method (e.g. Western Blot); or any one of the following prior to randomization: detectable HIV p24 antigen, quantifiable plasma HIV RNA, or proviral DNA.

Greater than or equal to 18 years of age.

The following clinical laboratory values obtained within 45 days prior to randomization:

One CD4+ T cell count greater than or equal to 300 cells/mm(3). (For participants who are status post-splenectomy, also a CD4+ cell percentage on this occasion greater than or equal to 20%);

AST or ALT less than 5 times the upper limit of normal (ULN) range;

Total or direct bilirubin less than or equal to 2 X ULN (Participants with hyperbilirubinemia due to Gilbert's syndrome or indinavir or atazanavir therapy may have a serum bilirubin up to 5 X ULN);

Serum creatinine less than or equal to 2 mg/dl (177 micro mol/L);

Sodium within normal limits;

Granulocyte count greater than or equal to 1000/mm(3);

Hemoglobin greater than or equal to 10 gm/dl;

Platelet count greater than or equal to 50,000 cells/mm(3).

Ability to provide informed consent.

Ability to obtain HAART regimens consisting of greater than or equal to 1 protease inhibitor and greater than or equal to 2 nucleoside or nucleotide reverse transcriptase inhibitors.

EXCLUSION CRITERIA:

Any prior history of rIL-2 use.

Use of any approved or experimental antiretroviral drug (including hydroxyurea) within one year prior to randomization.

In the judgment of the clinician, any current indication for continuous antiretroviral therapy, or any contraindication to antiretroviral therapy.

Evidence of virological failure on a protease inhibitor- or nonnucleoside reverse transcriptase-based antiretroviral regimen.

Use of systemic corticosteroids, chemotherapy, or experimental cytotoxic drugs within 45 days prior to randomization.

Use of any agents (approved or experimental) with clinically significant immunomodulatory effects within 8 weeks prior to randomization.

History of any AIDS-defining illness or any of the following conditions: extrapulmonary Pneumocystis carinii disease; multi-dermatomal Herpes zoster (greater than or equal to 10 lesions in a non-contiguous site); American trypanosomiasis (Chagas disease) of the CNS; Penicillium marneffii disease; visceral leishmaniasis; non-Hodgkin's lymphoma of any cell-type; Hodgkin's lymphoma; bartonellosis; microsporidiosis (greater than 1 month's duration); nocardiosis; invasive aspergillosis; or Rhodococcus equi disease.

Concurrent malignancy requiring cytotoxic chemotherapy.

Any CNS abnormality that requires ongoing treatment with antiseizure medication.

Current or historical autoimmune/inflammatory diseases including:

Inflammatory bowel disease, psoriasis, optic neuritis, or any autoimmune/inflammatory diseases with potentially life-threatening complications.

Significant cardiac, pulmonary, renal, hepatic, gastrointestinal, CNS, psychiatric disease or illicit substance use/abuse that in the opinion of the investigator would make the participant a poor candidate for study participation.

Pregnancy (for women of childbearing potential, a negative pregnancy test, urine or serum, is required within 14 days prior to randomization).

Breastfeeding.

Special Instructions:

Currently Not Provided

Keywords:

Immunomodulator

Antiretroviral-Sparing

T Lymphocytes

Intermittent Therapy

Recruitment Keyword(s):

HIV

ARV

IL-2

HAART Naive

Condition(s):

HIV Infections

HIV

Investigational Drug(s):

Interleukin-2, Proleukin

Investigational Device(s):

None

Intervention(s):

Drug: Interleukin-2, Proleukin

Drug: Interleukin-2, Proleukin

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Vittinghoff E, Scheer S, O'Malley P, Colfax G, Holmberg SD, Buchbinder SP. Combination antiretroviral therapy and recent declines in AIDS incidence and mortality. J Infect Dis. 1999 Mar;179(3):717-20.

Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, d'Arminio Monforte A, Yust I, Bruun JN, Phillips AN, Lundgren JD. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet. 1998 Nov28;352(9142):1725-30.

Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60.

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