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Safety and Effectiveness of Adding Either an HIV Vaccine, Interleukin-2, or Both to a Patient's Anti-HIV Drug Combination

Phase 2
Completed
Conditions
HIV Infections
Registration Number
NCT00006291
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

The purpose of this study is to see if adding an HIV vaccine (ALVAC-HIV vCP1452), IL-2 (interleukin-2, a protein found in the blood that helps boost the immune system), or both to anti-HIV-drug therapy is safe, tolerable, and effective in controlling viral load (level of HIV in the body). (This study has been changed to clarify drug name.) Anti-HIV drugs can help reduce a patient's viral load. However, HIV can still remain in CD4 cells (cells of the immune system that help fight infection). Combining an HIV vaccine, IL-2, or both with anti-HIV drugs may help reduce the number of HIV-infected cells.

Detailed Description

The most important goal for designing future therapeutic interventions is to understand the nature of persistent HIV infection in patients successfully treated with potent antiretroviral therapy and to develop strategies to promote the clearance of these reservoirs or at least long-term suppression of these reservoirs. If latently infected cells are able to persist for a long period (despite effective suppression of de novo infection) primarily because immune clearance is not being adequately stimulated by viral antigen, then HIV-specific immunization is a reasonable strategy to enhance the clearance of these cells. Stimulating effective HIV-specific cellular immune responses at a time when plasma viremia is maximally suppressed also may contribute to the long-term containment of HIV replication on potent antiretroviral therapy. A second component to be evaluated in this trial is whether broad, cyclical activation of T cells with IL-2 will increase the activation of HIV proviral gene expression and thereby render target cells susceptible to immune-mediated clearance. This pathogenesis-based clinical trial will explore the potential for these novel treatment strategies (HIV-specific immunization and IL-2, alone and in combination) to complement the effects of potent antiretroviral therapy by promoting more effective immunologic control of HIV-1 replication.

This study is divided into 3 steps.

STEP I: Patients continue to receive their stable potent antiretroviral therapy and are randomized to 1 of 4 arms:

Arm A: Vaccine placebo \[AS PER AMENDMENT 08/23/01: ALVAC\]; Arm B: Canarypox HIV-specific immunogen \[AS PER AMENDMENT 08/23/01: ALVAC-HIV\] (vCP1452); Arm C: 8-week cycles of IL-2 plus vaccine placebo \[AS PER AMENDMENT 08/23/01: ALVAC\]; Arm D: 8-week cycles of IL-2 plus canarypox HIV-specific immunogen \[AS PER AMENDMENT 08/23/01: ALVAC-HIV\] (vCP1452).

Patients receive vaccine (or vaccine placebo) injections at Weeks 0, 8, 16, 24, and 48. IL-2 injections are synchronized with vaccine injections. IL-2 is given open-label while vCP1452 is double-blinded. Patients must be on Step I for a minimum of 51 weeks \[AS PER AMENDMENT 08/23/01: prior to entry into Step II\].

STEP II: Patients stop study medications and interrupt potent antiretroviral therapy for \[AS PER AMENDMENT 08/23/01: "6 to 16" has been replaced by the following text: a minimum of 12\] weeks. Patients whose viral load during Step II remains \[AS PER AMENDMENT 08/23/01: at or\] below 5,000 copies/ml \[AS PER AMENDMENT 08/23/01: and whose CD4 count is 200 cells/mm3 or more\] are encouraged to remain off antiretroviral medications and continue viral-load monitoring for up to an additional 10 weeks. These patients are followed \[AS PER AMENDMENT 08/23/01: "for up to 16 weeks" has been replaced by the following text: through Week 74\] on Step II and must register to Step III only if their viral load increases to 50,000 copies/ml or greater, their CD4 count decreases to below 200 cells/mm3, or if their primary care physician recommends resuming antiretrovirals.

STEP III: Patients resume their original potent antiretroviral therapy regimen for 6 to 10 weeks and are monitored for a minimum of 6 weeks. If patients do not achieve a viral load below 50 copies/ml during those 6 weeks, they continue to be monitored for up to an additional 4 weeks until this degree of suppression is achieved with the same potent antiretroviral therapy regimen or another appropriate regimen.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (26)

Hosp. of the Univ. of Pennsylvania CRS

🇺🇸

Philadelphia, Pennsylvania, United States

Alabama Therapeutics CRS

🇺🇸

Birmingham, Alabama, United States

USC CRS

🇺🇸

Los Angeles, California, United States

UCLA CARE Center CRS

🇺🇸

Los Angeles, California, United States

Stanford CRS

🇺🇸

Palo Alto, California, United States

Ucsf Aids Crs

🇺🇸

San Francisco, California, United States

Santa Clara Valley Med. Ctr.

🇺🇸

San Jose, California, United States

San Mateo County AIDS Program

🇺🇸

San Mateo, California, United States

Marin County Dept. of Health & Human Services, HIV/AIDS Program & Specialty Clinic

🇺🇸

San Rafael, California, United States

Harbor-UCLA Med. Ctr. CRS

🇺🇸

Torrance, California, United States

University of Colorado Hospital CRS

🇺🇸

Aurora, Colorado, United States

Univ. of Miami AIDS CRS

🇺🇸

Miami, Florida, United States

The Ponce de Leon Ctr. CRS

🇺🇸

Atlanta, Georgia, United States

Northwestern University CRS

🇺🇸

Chicago, Illinois, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

🇺🇸

Indianapolis, Indiana, United States

Indiana Univ. School of Medicine, Wishard Memorial

🇺🇸

Indianapolis, Indiana, United States

Methodist Hosp. of Indiana

🇺🇸

Indianapolis, Indiana, United States

University of Minnesota, ACTU

🇺🇸

Minneapolis, Minnesota, United States

Beth Israel Med. Ctr., ACTU

🇺🇸

New York, New York, United States

NY Univ. HIV/AIDS CRS

🇺🇸

New York, New York, United States

Univ. of Rochester ACTG CRS

🇺🇸

Rochester, New York, United States

Unc Aids Crs

🇺🇸

Chapel Hill, North Carolina, United States

Vanderbilt Therapeutics CRS

🇺🇸

Nashville, Tennessee, United States

Univ. of Texas Medical Branch, ACTU

🇺🇸

Galveston, Texas, United States

Puerto Rico-AIDS CRS

🇵🇷

San Juan, Puerto Rico

Univ. of Hawaii at Manoa, Leahi Hosp.

🇺🇸

Honolulu, Hawaii, United States

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