Clinical trial NCT00038259: Interleukin-2 (IL-2) Treatment for HIV Infected Patients Who Have Interrupted Their Anti-HIV Drug Therapy
Official title: An Exploratory, Open-Label, Randomized Trial to Evaluate the Ability of Interleukin-2 (IL-2) to Enhance HIV-Specific Immunity and Influence the Time to Virologic Relapse Following Withdrawal of Potent Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Interleukin-2
Drug Administration Schedule
CD4 Lymphocyte Count
Anti-HIV Agents
Viral Load
Treatment Interruption
Treatment Experienced
STI
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2002-05-30
Enrollment: 21
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: When an HIV infected person taking strong anti-HIV drugs temporarily stops taking them, viral load rises and the body's immune system is exposed to more HIV. This may lead to the body mounting a better immune response against the virus. The purpose of this study is to find out if taking interleukin-2 (also called IL-2 or aldesleukin) while stopping anti-HIV drugs for short periods of time can help patients control their HIV viral load.

Study hypothesis: Patients in this study will have lower virologic rebound and will maintain their CD4 cell counts for a longer time than other patients in comparative studies.

Detailed description: Structured treatment interruptions (STIs) may stimulate an anti-HIV immune response. Evidence suggests that IL-2, which increases CD4 counts, could also enhance specific immune responses to HIV. Enhanced immune responses could influence the magnitude of and the time to virologic rebound following treatment discontinuation. This study will compare the viral loads present after 12 weeks of an antiretroviral therapy (ART) interruption period between patients who have received different dosing regimens of IL-2 and have taken part in at least two STIs.

This study will last 40 to 104 weeks. IL-2 is provided as part of this study; potent ART is not provided. Patients in this study will receive potent ART with at least two scheduled potent ART interruptions. Patients will be randomly assigned to one of two treatment arms. Arm A patients will receive low-dose injections of IL-2 for 3 weeks, during the last 2 weeks of potent ART interruption periods and the first week of restarting potent ART. Arm B patients will receive high-dose injections of IL-2 during the first 5 days of restarting potent ART after the interruption period. The first two ART interruptions are 4 weeks in duration, followed by 12 weeks back on ART. Depending on the patient's viral load and CD4 count at Week 32, patients will either enter a third potent ART interruption for 12 to 48 weeks or will continue ART. No IL-2 will be given with the third scheduled potent ART interruption. Throughout the study, participants will have physical exams and laboratory tests, including measurements of viral load and CD4 count.

Eligibility criteria: Note: ACTG A5132 closed to accrual on 11/01/04.

Inclusion Criteria:

* HIV infected
* CD4 cell count of 300 cells/mm3 or more within 30 days prior to study entry
* HIV viral load of less than 50 copies/ml within 30 days prior to study entry
* Anti-HIV drug regimen of at least 3 anti-HIV drugs for at least 6 months immediately prior to study entry
* Documented pretherapy plasma HIV viral load measured within 6 months of starting ART
* Willing to use acceptable methods of contraception

Exclusion Criteria:

* HIV viral load of 50 copies/ml or more within 60 days before study entry
* Current use of experimental anti-HIV drugs other than FDA sanctioned investigational drugs
* Abacavir as part of anti-HIV regimen within 8 weeks prior to study entry
* Pregnant or breastfeeding
* History of autoimmune disease, except for stable autoimmune thyroid disease
* Heart problems or on certain medications for treatment of heart problems
* Cancer requiring chemotherapy
* Untreated thyroid disease
* Disease of the central nervous system that has been active within 1 year prior to study entry
* Uncontrolled diabetes
* Allergies to the study medications
* Other illnesses that would make it inappropriate for patients to participate in the study
* Immunomodulatory therapy within 4 weeks prior to study entry
* Hydroxyurea within 6 months prior to study entry
* Drug or alcohol use that, in the opinion of the investigator, would interfere with the study
* Psychiatric or mental impairment that would affect compliance

Primary outcomes:
measure: Mean of log10 HIV-1 RNA copies/ml obtained at Weeks 11 and 12 following the final interruption of potent antiretroviral therapy
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Sacramento
country: United States
facility: Univ. of California Davis Med. Ctr., ACTU
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med. Ctr.
state: California
city: San Mateo
country: United States
facility: San Mateo County AIDS Program
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Galveston
country: United States
facility: Univ. of Texas Medical Branch, ACTU
state: Texas
Study officials:
affiliation: University of California, Davis
name: Richard M. Pollard, MD
role: STUDY_CHAIR
References:
citation: Carr A, Emery S, Lloyd A, Hoy J, Garsia R, French M, Stewart G, Fyfe G, Cooper DA. Outpatient continuous intravenous interleukin-2 or subcutaneous, polyethylene glycol-modified interleukin-2 in human immunodeficiency virus-infected patients: a randomized, controlled, multicenter study. Australian IL-2 Study Group. J Infect Dis. 1998 Oct;178(4):992-9. doi: 10.1086/515653.
citation: Kovacs JA, Baseler M, Dewar RJ, Vogel S, Davey RT Jr, Falloon J, Polis MA, Walker RE, Stevens R, Salzman NP, Lane HC. Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study. N Engl J Med. 1995 Mar 2;332(9):567-75. doi: 10.1056/NEJM199503023320904.
citation: Kovacs JA, Vogel S, Albert JM, Falloon J, Davey RT Jr, Walker RE, Polis MA, Spooner K, Metcalf JA, Baseler M, Fyfe G, Lane HC. Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. N Engl J Med. 1996 Oct 31;335(18):1350-6. doi: 10.1056/NEJM199610313351803.
citation: Lafeuillade A, Poggi C, Hittinger G, Counillon E, Emilie D. Predictors of plasma human immunodeficiency virus type 1 RNA control after discontinuation of highly active antiretroviral therapy initiated at acute infection combined with structured treatment interruptions and immune-based therapies. J Infect Dis. 2003 Nov 15;188(10):1426-32. doi: 10.1086/379251. Epub 2003 Oct 27.
citation: Pett SL, Kelleher AD. Cytokine therapies in HIV-1 infection: present and future. Expert Rev Anti Infect Ther. 2003 Jun;1(1):83-96. doi: 10.1586/14787210.1.1.83.
citation: Bosch RJ, Pollard RB, Landay A, Aga E, Fox L, Mitsuyasu R; AIDS Clinical Trials Group A5132 Team. A randomized trial of interleukin-2 during withdrawal of antiretroviral treatment. J Interferon Cytokine Res. 2011 Jun;31(6):481-3. doi: 10.1089/jir.2010.0119. Epub 2011 Feb 3.