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
Some of the blood drawn for this study is used for genetic tests, and some blood is
collected and stored for future studies.
The purpose of this study is to compare the effects of subcutaneous (SC) recombinant
interleukin-2 (rIL-2) administered with and without concomitant peri-cycle highly active
antiretroviral therapy (HAART) to no therapy on CD4+ T lymphocyte count in patients with
HIV-1 infection and CD4+ T lymphocyte count greater than or equal to 300 cells/mm(3).
- 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
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).