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No Clinical Benefit from Remune^TM

Therapeutic vaccination with HIV-1 Immunogen added to antiretroviral therapy did not lengthen disease-free survival or time to treatment failure compared with antiretroviral therapy alone.

HIV-1 Immunogen is derived from whole inactivated HIV stripped of its envelope proteins and conjugated with incomplete Freund adjuvant (IFA). Currently in development under the trade name Remune^TM, this immune-based therapy had been shown to increase immune responses to HIV in patients already infected with the virus: an approach that has become known as therapeutic vaccination. This large study -- which received mixed manufacturer and academic funding -- evaluated whether this strategy would improve clinical outcome.

More than 2500 patients were enrolled in the study through 77 participating centers in the U.S. between March 1996 and May 1997. They were eligible if they had clinically stable HIV disease, no prior history of an AIDS-defining event (exclusive of Kaposi's sarcoma), and a baseline CD4 count between 300 cells/mm³ and 549 cells/mm³. HIV-1 Immunogen was given as an intramuscular injection every 12 weeks and compared in a double-blind fashion with placebo, which consisted only of IFA. All approved and investigational antiretroviral therapy was allowed, and regimens were not dictated by the trial. The primary endpoint was time to the development of an AIDS-defining OI or death.

In May 1999, the study's Data Safety Monitoring Board -- meeting for its second of 3 scheduled interim efficacy and safety analyses -- recommended that the trial be terminated early due to lack of difference between the 2 study arms. There were no differences between the 2 groups in time to HIV disease progression, overall survival, or (in a virologic substudy) time to antiretroviral treatment failure. Although both sides experienced increases in CD4-cell counts, the increase in the treatment group was greater by approximately 10 cells/mm³: a slight but statistically significant difference. Aside from local reactions to the vaccination, there was no significant difference between the 2 groups in adverse events.

This study shows that HIV-1 Immunogen is unlikely to improve clinical outcome or time to virologic failure in patients who are treated with standard combination antiretroviral therapy. These findings have been the source of significant controversy between the study investigators and the manufacturer, and led to withholding by the manufacturer of some of the data accrued during the study. It should be emphasized, however, that the negative results presented here do not preclude the potential benefits of HIV-1 Immunogen in other contexts (e.g., as an adjunct to structured treatment interruptions or in combination with other immune-based therapies). Such studies are currently being performed.

— Paul Sax, MD

Published in Journal Watch HIV/AIDS Clinical Care January 1, 2001

Citation(s):

Kahn JO et al. Evaluation of HIV-1 Immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549 x 10⁶/L CD4 Cell Counts. JAMA 2000 Nov 1; 284: 2193-202.

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