Treatment With Interleukin-2 (IL-2) Plus Combination Anti-HIV-Drug Therapy (HAART) for Patients Formerly in ACTG 328

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00000923
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : May 21, 2012
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

This study examines the long-term effects of interleukin-2 (IL-2) in combination with anti-HIV drugs, or highly active antiretroviral therapy (HAART). The purpose of this study is to see if IL-2 can increase the number of CD4 cells (cells of the immune system which fight infection) in HIV-infected patients who have completed ACTG 328.

HAART is often successful in decreasing viral load (level of HIV in the blood), but these drugs have not been able to restore the immune systems of HIV-infected patients. IL-2 is a substance naturally produced by the body's immune cells. In ACTG 328, IL-2 is tested to see if it can increase the number of CD4 cells and "boost" a patient's immune system. This study is a follow-up to ACTG 328 so that patients who are benefiting from IL-2 can continue to take it and patients in the control group who do not receive IL-2 can start taking it.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: Indinavir sulfate Drug: Lamivudine Drug: Stavudine Drug: Zidovudine Drug: Didanosine Drug: Aldesleukin Not Applicable

Detailed Description:

HIV disease is characterized by a progressive decline in CD4 cells and an increase in viral burden. Although antiretroviral therapy has been successful in controlling viral levels, its effects on CD4 cell counts have been modest. Intermittently administered IL-2 in the presence of HAART has been shown to increase CD4 cell counts, decrease lymphocyte activation markers, and increase certain lymphocyte functional activity in patients with early-stage HIV infection. ACTG 328 evaluated the effects of intravenous and/or subcutaneously administered IL-2 in conjunction with HAART in a group of more advanced HIV-infected patients over an 18- to 22-month period. As patients were enrolled in this study over an 18-month period, a follow-up protocol is required to provide continued IL-2 therapy for patients responding to IL-2 and patients in the control group who wish to receive this drug.

This study enrolls patients who participated in ACTG 328. Patients in Arm I of ACTG 328 (the control group receiving HAART only) who have a viral load of 5,000 copies/ml or less register for Step II. Patients in Step II receive subcutaneous [SC] IL-2 in combination with HAART. IL-2 is administered for 5 days every 8 weeks for the first 3 cycles. For subsequent cycles, the interval between cycles may be extended in 8-week increments for a maximum of 24 weeks, provided the patient's bimonthly CD4 count exceeds 500 cells/mm3. Patients in Arm I who have a viral load greater than 5,000 copies/ml register for Step I which requires a change in antiretroviral therapy. Patients who then achieve viral levels of 5,000 copies/ml or less may begin to receive IL-2 no earlier than 4 weeks and no later than 12 weeks after the change in HAART regimen. Patients whose viral load remains above 5,000 copies/ml for 12 weeks after the change in drug regimen are discontinued from the study. Patients in Arms II or III of ACTG 328 (IL-2-containing arms) who have had a 25 percent or greater increase in CD4 cell count above their Week 11 value and have a viral load of 5,000 copies/ml or less continue on SC IL-2 and HAART. Patients who meet the CD4 criteria but whose viral load is above 5,000 copies/ml change their HAART regimen. After a minimum of 4 weeks and a maximum of 12 weeks, these patients may receive IL-2 provided they have a viral load of 5,000 copies/ml or less. For this study, HAART is defined as one protease inhibitor and two nucleoside analogues. [AS PER AMENDMENT 9/16/99: All patients must receive a protease inhibitor or, with permission of the chair, a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus either two nucleoside reverse transcriptase inhibitors (NRTIs) or another protease inhibitor or NNRTI.] The protease inhibitor provided on this study is indinavir (IDV). The nucleoside analogue combinations provided on this study are as follows: zidovudine (ZDV) plus didanosine (ddI), ZDV plus lamivudine (3TC), stavudine (d4T) plus 3TC, or d4T plus ddI. Other antiretroviral drugs may be used but are not provided by this study. Patients are monitored for CD4 counts at bimonthly intervals after the first IL-2 dose. CD4 counts and plasma storage for HIV RNA are done within 96 hours prior to each cycle of IL-2. Safety laboratory evaluations are obtained prior to and at the conclusion of each IL-2 course. TSH (thyroid-stimulating hormone), DTH skin testing, and real-time plasma HIV RNA are obtained at 6-month intervals.

Study Type : Interventional  (Clinical Trial)
Enrollment : 110 participants
Primary Purpose: Treatment
Official Title: Treatment Rollover for Subjects Formerly on ACTG 328 With Subcutaneous Interleukin-2 (IL-2) in Combination With Highly Active Antiretroviral Therapy (HAART)
Actual Study Completion Date : August 2004

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00000923

United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States, 35294
United States, California
Los Angeles, California, United States, 900331079
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Iowa
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States, 52242
United States, Louisiana
Tulane Univ. A1701 CRS
New Orleans, Louisiana, United States, 70112
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States, 63112
Washington U CRS
St. Louis, Missouri, United States
United States, New York
Mt. Sinai Med. Ctr. A0404 CRS
New York, New York, United States, 10029
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 432101228
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Ronald Mitsuyasu
Study Chair: Richard Pollard

Publications of Results:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00000923     History of Changes
Other Study ID Numbers: A5051
10205 ( Registry Identifier: DAIDS ES Registry Number )
Substudy ACTG A5052s
Substudy ACTG A5053s
Substudy ACTG A5054s
Substudy ACTG A5094s
ACTG A5051
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: May 21, 2012
Last Verified: May 2012

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Therapy, Combination
CD4 Lymphocyte Count
Anti-HIV Agents
Viral Load

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents