Effect of Intermittent Aldesleukin Treatment With or Without Anti-HIV Drugs in HIV Infected People
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Drug: Aldesleukin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized, Open-Label, International Study of Subcutaneous Recombinant Interleukin-2 (rIL-2, Aldesleukin) With and Without Concomitant Antiretroviral Therapy in Patients With HIV-1 Infection and CD4+ Cell Counts of 300 Cells/mm3 or More: Study of Aldesleukin With and Without Concomitant Antiretroviral Therapy |
- Mean change in CD4+ T lymphocyte count [ Time Frame: Through Week 32 ] [ Designated as safety issue: No ]
- HIV disease progression events and death between IL-2 recipients and controls [ Time Frame: At Month 31 ] [ Designated as safety issue: Yes ]
- Grade 3 and 4 events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Therapy modification as defined by the protocol [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Plasma HIV RNA [ Time Frame: At Week 32, Month 12, and Month 31 ] [ Designated as safety issue: No ]
- CD4 T lymphocyte count [ Time Frame: At Months 12 and 31 ] [ Designated as safety issue: No ]
- HIV-1 genotype changes [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Fasting lipid profile and thyroid stimulating hormone and hepatic transaminase levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Timing of commencement of continuous antiretrovirals [ Time Frame: At Month 31 ] [ Designated as safety issue: No ]
| Enrollment: | 267 |
| Study Start Date: | September 2005 |
| Study Completion Date: | February 2011 |
| Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
No Intervention: 1
Participants will receive no aldesleukin or HAART
|
|
|
Experimental: 2
Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Some Group 2 participants may take part in additional cycles of aldesleukin if they meet certain study criteria.
|
Drug: Aldesleukin
7.5 MIU injected intramuscularly
Other Name: Proleukin
|
|
Experimental: 3
Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group 3 participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). Some Group 3 participants may take part in additional cycles of aldesleukin if they meet certain study criteria.
|
Drug: Aldesleukin
7.5 MIU injected intramuscularly
Other Name: Proleukin
|
Detailed Description:
Highly active antiretroviral therapy (HAART) has dramatically improved prognosis and lowered morbidity and mortality rates for HIV infected patients. However, significant drug toxicities, difficulties with patient compliance to HAART regimens, and development of drug resistance highlight the need for less toxic, immune-based strategies. Aldesleukin is a synthetic protein that can increase CD4 counts; it is currently approved by the Food and Drug Administration (FDA) for use in patients with metastatic melanoma and renal cell carcinoma. Previous studies of aldesleukin in HIV infected patients indicated that increased CD4 counts can persist for years after aldesleukin administration, and aldesleukin given with HAART may also lead to significant lowering of viral load. This study will examine the immunologic effects of intermittent cycles of aldesleukin administered with and without HAART as compared to no therapy in HIV infected patients.
This study will last approximately 31 months. Participants will be randomly assigned to one of three groups at study entry. Group A will receive no aldesleukin or HAART. Group B will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Group C will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group C participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). HAART will not be provided by the study. Some Group B and C participants may take part in additional cycles of aldesleukin if they meet certain study criteria.
All participants in this study will have at least 8 study visits; these visits will occur at study entry and Weeks 4, 8, 12, 16, 20, 24, and 32. Blood collection will occur at all visits and will include tests for CD4 count and viral load. Groups B and C will have additional blood collection within 4 days prior to the start of each aldesleukin cycle. On the last day of each aldesleukin cycle, Groups B and C will be assessed for toxicities, adverse events, and adherence to the aldesleukin daily injections; they will also have another blood collection. Group C participants will have an additional blood collection for HIV genotyping after they have completed their third aldesleukin cycle. Extended follow-up visits will occur approximately every 4 months for an additional two years. Blood collection will occur at these visits and will include tests for CD4 count, viral load, and other laboratory tests.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Show 36 Study Locations| Study Chair: | Jorge Tavel, MD | National Institute for Allergy and Infectious Diseases, National Institutes of Health |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00110812 History of Changes |
| Other Study ID Numbers: | ESPRIT 002, 10053 |
| Study First Received: | May 13, 2005 |
| Last Updated: | May 24, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
Treatment Naive IL-2 rIL-2 |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Aldesleukin Interleukin-2 |
Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 23, 2013