Please select the eligibility criteria that correspond to the clinical trial below.
Title: STALWART: A Randomized, Open-Label, International Study of Subcutaneous Recombinant Interleukin-2 With and Without Concomitant Antiretroviral Therapy in Patients With HIV-1 Infection and CD4+ Cell Counts of 300 Cells/mm3 or More
Brief Summary: The purpose of this study is to determine the effect of short cycles of recombinant interleukin-2 (also known as rIL-2 or aldesleukin) given with or without anti-HIV drugs in HIV infected patients. The effects will be compared with a study group that receives no IL-2 or antiretroviral therapy.

Study hypothesis: Intermittent aldesleukin, when given without antiretroviral therapy to patients with early HIV infection, will produce no change in HIV viral load and increases in CD4+ T lymphocyte counts comparable to aldesleukin administered with antiretrovirals.


Options:
A: Inclusion Criteria:

* HIV infected
* CD4 count of 300 cells/mm3 or more
* Access to a HAART regimen consisting of 1 or more protease inhibitors (PIs) and 2 or more nucleoside or nucleotide reverse transcriptase inhibitors

Exclusion Criteria:

* Prior use of aldesleukin
* Approved or experimental antiretroviral drug (including hydroxyurea) within 1 year prior to study entry
* Evidence of virologic failure on a PI- or nonnucleoside-based HAART regimen
* Any current indication for continuous HAART, in the opinion of the investigator
* Any contraindication to HAART, in the opinion of the investigator
* Systemic corticosteroids, chemotherapy, or experimental cytotoxic drugs within 45 days of randomization
* Approved or experimental agents with clinically significant immunomodulatory effects within 8 weeks prior to randomization
* History of any AIDS-defining illness or certain other diseases. More information on this criterion can be found in the protocol.
* Concurrent cancer requiring cytotoxic therapy
* Any central nervous system (CNS) abnormality requiring ongoing treatment with antiseizure medication
* Current or prior autoimmune or inflammatory diseases, including inflammatory bowel disease, psoriasis, optic neuritis, or any other autoimmune or inflammatory diseases with potentially life-threatening complications
* Significant heart, lung, kidney, liver, gastrointestinal, CNS, or psychiatric disease OR illicit substance use or abuse that, in the opinion of the investigator, would interfere with the study
* Pregnancy or breastfeeding
B: Inclusion Criteria:

* HIV positive
* Have a CD4 cell count of 300 cells/mm3 or more within 45 days of study entry
* Are on combination anti-HIV therapy or are beginning anti-HIV therapy at the time of study entry
* Are at least 18 years old

Exclusion Criteria:

* Have received IL-2 before
* Have cancer requiring chemotherapy
* Have evidence of active clinical disease within the past year for any AIDS-defining illness or certain other conditions such as herpes zoster or Chagas disease. (This study has been changed. Previously, patients were ineligible if they had a history of any AIDS-defining illness or certain other conditions.)
* Have used certain medications, such as corticosteroids or drugs affecting the immune system, in the 45 days before study entry
* Have a nervous system disorder requiring antiseizure medication
* Have an autoimmune or inflammatory disease such as inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), psoriasis, optic neuritis, or any autoimmune/inflammatory diseases with potentially life-threatening complications
* Are pregnant or breastfeeding
C: * INCLUSION CRITERIA:

Subjects are eligible for this study if they have been on greater than or equal to 2 ART for greater than or equal to 4 months prior to randomization, with no change in the type of ART received during this 4-month period of time. For subjects who receive only 2 ART, at least one of these two medications should be a protease inhibitor (PI). Subjects are not eligible if ART is discontinued for a cumulative period of 7 or more days during the 4 months prior to randomization.

Subjects with documented HIV-1 infection. Acceptable documentation consists of either of the following:

Positive HIV-1 ELISA test and Western Blot;

Detectable plasma viral load measurement (greater than 500 RNA copies/mL using an ultrasensitive bDNA or PCR test or greater than 1500 RNA copies/mL using a non-ultrasensitive bDNA or PCR test).

CD4+ T cell counts: mean of 2 points obtained within 4 calendar months of randomization greater than or equal to 50 and less than 300 cells/mm(3). The first CD4+ count should be the most recent documented historical value and should be greater than or equal to 50 and less than 300 cells/mm(3); the second point should be pre-study visit 1.

Viral load less than 10,000 copies/mL, at 2 time points within 4 calendar months of randomization. The first viral load should be the most recent documented historical value and should be less than 10,000 copies/mL; the second time point should be pre-study visit 1.

Karnofsky performance status greater than or equal to 80%.

Age greater than or equal to 18 years old.

Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to randomization. They must also understand that if they are randomized to the IL-2 group, they must practice effective contraception during their first 2 years of study participation. Pregnancy is discouraged among IL-2 recipients, but if an IL-2 recipient wishes to become pregnant after two years of trial participation she must alert the investigator prior to interruption of contraception. The potential for risk to the fetus must be carefully discussed with the subject before contraception is interrupted. Effective contraception will be continued for at least 24 hours following the interruption of IL-2 therapy. IL-2 will be held throughout the period of time during which the subject is not practicing effective birth control, throughout the pregnancy, and throughout any period of breast feeding. If oral contraceptive therapy is resumed after a period of interruption, IL-2 dosing will be delayed for 1 month following the reinstatement of oral contraceptive therapy. The subject must have a negative pregnancy test result prior to dosing with IL-2 after a lapse in effective contraception.

The following laboratory criteria must be fulfilled within 28 days of enrollment in the study:

Serum AST of less than or equal to 5 times upper limit of normal range (ULN);

Serum bilirubin less than or equal 2 times ULN (patients with Gilbert's syndrome or protease inhibitor-induced hyperbilirubinemia must have a serum bilirubin less than or equal to five times ULN);

Amylase less than 2.0 times ULN (hyperamylasemia that is determined to be non-pancreatic in origin does not necessarily constitute an exclusion to enrollment);

Less than 2 + proteinuria;

Serum creatinine less than or equal to 1.5 times ULN;

Absolute neutrophil count greater than or equal to 1000 cells/mm(3);

Hemoglobin of greater than or equal to 9.5 g/dL;

Platelet count of greater than or equal to 75,000/mm(3);

Negative HTLV-1 result.

Agree to participate in the study for 4.5 to 7.5 years.

Written informed consent.

EXCLUSION CRITERIA:

Certain AIDS-defining illnesses. These conditions include:

Patients with no prior history of AIDS-defining events are eligible for SILCAAT;

Patients with a prior medical history of one or more of the following AIDS-defining events are eligible only under the condition specified below:

Lymphoma (other than lymphoma of the brain): Patients with a history of successfully treated lymphoma are eligible, provided full remission was obtained at least 5 years prior to randomization. Full remission (or complete response) is defined as the absence of clinically detectable disease with normalization of any previously abnormal radiographic studies, and bone marrow examination. Patients with bone marrow positive lymphoma prior to chemotherapy must have had two repeat bone marrow examinations negative for lymphoma after chemotherapy at least 12 months prior to randomization.

Esophageal candidiasis; Patients with a prior history of successfully treated esophageal candidiasis are eligible if they have been free of clinical symptoms in the absence of antifungal suppressive therapy for at least 12 months prior to randomization. Documentation of a negative endoscopy should ideally be on record.

Invasive cervical cancer: Patients with a prior history of invasive cervical cancer are eligible if complete local cure of the cancer has been documented at least 5 years prior to randomization and there has been no evidence of metastatic disease at any time.

Kaposi's sarcoma: Patients are eligible if mucocutaneous lesions have been resolved or clinically stable for at least 12 months prior to randomization. Subjects with a history of visceral KS are excluded.

Mycobacterium tuberculosis or M. kansasii: Patients are eligible if clinical resolution of disease occurred at least 12 months prior to randomization and previously abnormal imaging studies have been normal, or stable after improvement, for at least 12 months prior to randomization. Documentation of microbiologic cure should ideally be on record. Therapy for tuberculosis or M. kansasii must have been completed at least 12 months prior to randomization.

Pneumocystis carinii pneumonia (PCP): Patients are eligible if clinical resolution of the disease occurred at least 12 months prior to randomization and previously abnormal imaging studies have been normal, or stable after improvement, for at least 12 months prior to randomization.

Recurrent pneumonia: Patients are eligible if there has been no evidence of pneumonia within 12 months prior to randomization.

Recurrent Salmonella septicemia: Patients are eligible if there has been no evidence of Salmonella septicemia within 12 months prior to randomization.

Wasting syndrome due to HIV: Patients are eligible for enrollment in SILCAAT if they have had a stable or increasing weight for at least 12 months prior to randomization.

Toxoplasmosis of the brain: Patients are eligible if their disease has been clinically resolved for at least 12 months prior to randomization. In addition, these patients must have a MRI or contrast CT scan of the brain performed within 1 month prior to randomization showing no sign of active disease.

Chronic intestinal cryptosporidiosis and chronic intestinal isosporiasis (greater than 1 month duration): Patients are eligible if their disease has been clinically resolved and they have been off specific therapy for at least 12 months prior to randomization. In addition, these patients must have at least one stool specimen documenting clearance of parasitic infection obtained within 1 month prior to randomization.

Patients with a history of any other AIDS-defining conditions as listed in the CDC 1993 Case Definition are not eligible for SILCAAT.

Subjects must not have clinically significant cardiac, pulmonary, thyroid, kidney or neurologic impairment, hemostasis disorder, or significant medical condition that would, in the opinion of the principal investigator, affect patient safety and/or compliance. In addition, subjects with the following conditions are specifically excluded: autoimmune disease, inflammatory bowel disease, psoriasis, optic neuritis, congestive heart failure, active ischemic heart disease, uncontrolled diabetes mellitus, moderate or severe hemophilia ( less than or equal to 5% of normal factor VIII levels), seizure disorder, uncontrolled hypothyroidism, cirrhosis and a prior medical history of transplantation. If an investigator has any reservations about the safety of enrolling a particular subject, he/she should consult with the medical monitor prior to screening the subject.

Psychiatric or cognitive disturbance or illness, or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect patient safety and/or compliance.

Malignancy requiring systemic chemotherapy within 12 months prior to randomization.

Current use or use within 4 weeks prior to randomization of systemic corticosteroid therapy or any agent, licensed or experimental, with known immunomodulatory effects (use of erythropoietin and anabolic steroids is allowed).

Current use, or use within 4 weeks of randomization of cytotoxic agents or antimetabolites; current use or use within 4 months of randomization of hydroxyurea or intravenous immunoglobulin.

Pregnant or lactating subjects.

Prior therapy with IL-2.

Prior participation in an ongoing IL-2 trial, eg, the ESPRIT trial.

Protocol non-compliance in a previous IL-2 trial.

Subjects with evidence of active acute infection within 2 weeks of randomization.
D: Inclusion Criteria

Patients may be eligible for this study if they:

* Are HIV-positive.
* Have completed at least 84 weeks of treatment on ACTG 328.
* Have had a 25 percent or greater increase in CD4 cell count above the ACTG 328 Week 11 value (only applies to patients who received IL-2 during ACTG 328).
* Are 18 years of age or older.
* Agree to practice abstinence or use a barrier method of birth control (such as condoms) during the study. (This study has been changed. Hormonal methods of birth control such as birth control pills are no longer allowed.)

Exclusion Criteria

Patients will not be eligible for this study if they:

* Have significant heart disease or are taking certain heart medications. Patients with hypertension who are being treated are eligible.
* Have taken certain medications that might affect the immune system within 4 weeks of study entry including corticosteroids, interferons, or thalidomide.
* Have taken rifampin, rifabutin, or St. John's wort within 7 days of study entry. (This study has been changed. St. John's wort was not in the original version.)
* Are taking certain investigational anti-HIV drugs.
* Are taking indinavir and any of the following within 2 weeks of study entry: cisapride, terfenadine, astemizole, midazolam, triazolam, ketoconazole, itraconazole, or delavirdine.
* Have cancer requiring chemotherapy. Local radiation therapy is allowed.
* Have untreated thyroid disease.
* Are allergic to albumin.
* Have a serious mental illness.
* Have a history of an autoimmune disease, including inflammatory bowel disease and psoriasis.
* Have a central nervous system disease or seizures, if these have been active within 1 year prior to study entry.
* Abuse drugs or alcohol.
* Are pregnant or breast-feeding.

Answer: A