A Phase II Study of Low-Dose Interleukin-2 by Subcutaneous Injection in Combination With Antiretroviral Therapy Versus Antiretroviral Therapy Alone in Patients With HIV-1 Infection and at Least 3 Months Stable Antiretroviral Therapy

• Status: Completed
• Trial end date: 2002-03-01
• Target enrollment: 0
• Participant gender: All

Summary

PRIMARY: To examine the effect of aldesleukin ( IL-2 ) on viral activity in the blood. To determine the safety of low-dose IL-2 in combination with antiretroviral therapy versus antiretroviral therapy alone.

SECONDARY: To examine delayed type hypersensitivity responses to skin test antigens and antibody responses to protein and polysaccharide vaccines.

The profound immune impairment that results from HIV-1 infection is due, at least in part, to the loss of CD4+ T cells and the cytokines these cells secrete, especially IL-2 and interferon-gamma. Antiretroviral agents do not directly address the problem of immune impairment. Replacement of IL-2 at nontoxic doses may prevent or delay clinical immunosuppression and its attendant opportunistic infections. Also, since patients with HIV-1 infection respond suboptimally to routine protein and polysaccharide immunizations, IL-2 may provide an adjuvant effect on vaccine responses.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Aldesleukin; Interleukin-2

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis.

• Therapy for an opportunistic infection that develops on study, with the exception of foscarnet for CMV disease or resistant Herpes simplex.

• Systemic corticosteroids ONLY IF given for no longer than 21 days for acute PCP.

• Topical corticosteroids to areas separate from a skin test or IL-2 injection site.

• Acyclovir up to 1000 mg/day as maintenance for recurrent genital Herpes.

• Erythropoietin and filgrastim.

• Antiemetics.

• Antibiotics as clinically indicated.

• Elective standard immunizations at week 8 or later.

Concurrent Treatment:

Allowed:

• Local radiation therapy.

Prior Medication: Required:

• Stable, approved antiretroviral therapy for at least 2 months (was 3 months, amended 3/26/96) prior to study entry.

Patients must have:

• HIV seropositivity.

• CD4 count 300 - 700 cells/mm3.

• Stable antiretroviral therapy for at least 2 months (was 3 months, amended 3/26/96) prior to study entry.

• No history of AIDS-defining illness except for limited cutaneous Kaposi's sarcoma.

• Normal EKG (isolated nonspecific ST and T wave changes permitted).

NOTE:

• This protocol is approved for prisoner participation.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy requiring systemic or local cytotoxic chemotherapy.

• Untreated thyroid disease.

• Asthma requiring intermittent or chronic inhalation or systemic therapy.

• Any medical condition that precludes study entry.

Concurrent Medication:

Excluded:

• Antianginal agents such as nitrates, calcium channel blockers, beta blockers, and antiarrhythmics.

• Systemic or local cytotoxic chemotherapy.

• Interferons.

• Interleukins other than study drug.

• Pentoxifylline ( Trental ).

• Acetylcysteine ( NAC ).

• Sargramostim ( GM-CSF ).

• Dinitrochlorobenzene ( DCNB ).

• Thymosin alpha 1.

• Thymopentin.

• Inosiplex ( Isoprinosine ).

• Polyribonucleoside ( Ampligen ).

• Ditiocarb sodium ( Imuthiol ).

• Therapeutic HIV vaccines.

• Investigational antiretroviral agents such as lamivudine ( 3TC ) and tat and protease inhibitors.

• Foscarnet.

• Aspirin.

• Immune globulin ( IVIG ).

• Thalidomide.

• Systemic corticosteroids (permitted for 21 days or less for PCP treatment only).

Concurrent Treatment:

Excluded:

• Ongoing transfusion.

Patients with the following prior conditions are excluded:

• History of autoimmune disease, including inflammatory bowel disease and psoriasis (although autoimmune thyroid disease that is stable is allowed).

• Clinically significant CNS disease or seizures that have been active within 1 year prior to study entry.

Prior Medication:

Excluded:

• IL-2 within 3 months prior to study entry.

• Any immunomodulatory therapy within 4 weeks prior to study entry.

• Foscarnet within 4 weeks prior to study entry.

• Acute therapy for an opportunistic infection within 14 days prior to study entry.

Active alcohol or substance abuse that would compromise study compliance.