Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha A

Article Abstract:

Potential therapies are currently being evaluated for use in treating the conditions associated with infection by human immunodeficiency virus type 1 (HIV-1, the virus responsible for AIDS). Emphasis has been on developing drugs that act on particular sites in the replicative cycles of these viruses. The inhibition of reverse transcriptase, which is involved in the replication of the virus, was first shown by the nucleoside analogue, 3'-azido-3'deoxythymidine, commonly known as AZT or zidovudine. The clinical use of this drug alone has been associated with toxic side effects as well as the development of resistant viral variants. Successful treatment appears to require the use of drugs and other types of clinical agents in various combinations, each directed at a different point in the replication cycle. Three clinical agents, recombinant soluble CD4 (rsCD4), recombinant interferon-alpha A (rIFN-alpha A) and AZT were evaluated in three-drug combinations, since various two-drug combinations of these agents demonstrated synergistic activity. Specifically prepared peripheral blood mononuclear cells (PBMC) and an H-9 cell clone were studied. All three agents inhibited HIV-1 cells synergistically, in both two- and three-drug combinations. The effects were observed in the two different cell types used over a range of drug concentrations and combinations. The impact of the various combinations upon viral reproduction was measured by p24 antigen production. In H-9 cells, the three-drug combination showed more effectiveness than any of the various two-drug combinations or single drug regimens employed. The three-drug combinations showed inhibition of viral replication over 28 days without any evidence of toxicity. These results suggest the potential benefit of clinical trials for these three drugs in combination. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, HIV infection, HIV infections, AIDS patients

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Two-drug combinations of Zidovudine, didanosine, and recombinant interferon-alpha A inhibit replication of zidovudine-resistant human immunodeficiency virus type 1 synergistically in vitro

Article Abstract:

AIDS is caused by infection with the human immunodeficiency virus (HIV-1), which attacks and destroys the immune system (the body's natural defense system for fighting infection). Current research is focusing on the development of new and effective treatments for AIDS. Zidovudine (also known as AZT) was one of the first drugs to be used for treating patients with AIDS. Studies have shown that this drug prolongs the lives of AIDS patients and prevents HIV-1 from reproducing or replicating itself. Two other drugs, didanosine (ddI) and recombinant interferon-alpha A (rIFN-A), have produced favorable results in the treatment of AIDS. However, in many cases, treatment with a single drug has resulted in drug toxicity or failure. Recently, a type of HIV-1 that is resistant to treatment with AZT was identified (AZT-resistant HIV-1). A study was performed to determine if a combination of AZT, ddI and rIFN-A could prevent the AZT-resistant HIV-1 from reproducing itself. Blood samples were taken from two AIDS patients before and after 26 months of treatment with AZT. White blood cells (called peripheral blood mononuclear cells) infected with AZT-resistant HIV-1 were isolated and treated with either AZT + ddI, AZT + rIFN-A, or ddI + rIFN-A. All the drug combinations tested were more effective in preventing the virus from reproducing itself than any one drug alone. It is concluded that a combination of drugs may be more effective in treating AIDS. In addition, combination therapy usually allows smaller doses to be used and, thus, may reduce the toxic side effects associated with drug treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

AIDS (Disease), Drug therapy, Combination, Combination drug therapy, Didanosine

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Strong in vitro synergy between the fusion inhibitor T-20 and the CXCR4 blocker AMD-3100

Article Abstract:

Two drugs that block different steps during the attachment of HIV to cell membranes appear to work better together than they do separately. One drug blocks the CXCR4 cell receptor for HIV and the other is a synthetic version of the viral protein gp41 that blocks fusion to cell membranes.

Research, HIV (Viruses), HIV, Virus receptors, Anti-HIV agents

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