Strategies for the combination therapy of HIV infection

Article Abstract:

Zidovudine (ZDV, which is the same as AZT) has been found to prolong the life of patients with AIDS or AIDS-related complex (ARC). In preliminary studies, two other drugs, 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI), have shown signs of being effective. However, there are limitations to the use of the available therapies, such as the toxicity occurring with long-term use. The human immunodeficiency virus (HIV) has been shown to become resistant to ZDV after approximately one year of treatment. It appears unlikely that a single drug will be the sole treatment for HIV infection or AIDS, and rather that a combination of various therapies will have to be used. Combination therapy involves either treatment with multiple drugs at the same time, or alternating or intermittent use of the drugs. Certain combinations of drugs which work against HIV appear to be synergistic (they have greater activity when used together than if their effects were just added together). This is important if the toxicity of the drugs is just additive. A combination of drugs can be used which affects the virus at different stages of replication and multiplication. An ideal combination of drugs is one that has synergistic activity against the virus and is antagonistic to toxicity (the combination of drugs is less toxic than the two drugs individually). Certain drugs may counteract the toxicities of other drugs. For example, cellular cytokines such as erythropoietin counteract the toxic effects of ZDV on bone marrow cells. If drugs have different toxicities, the intermittent or alternating use of the drugs may be beneficial. Combination therapy may also prevent or delay the virus from becoming resistant to the drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Usage, Drugs, Prevention, HIV infection, HIV infections, Drug resistance in microorganisms, Microbial drug resistance, Chemotherapy, Combination, Combination chemotherapy, Drug toxicity

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Differences in the interaction of HIV-1 and HIV-2 with CD4

Article Abstract:

The human immunodeficiency virus (HIV) exists as two major types, 1 and 2. The CD4 molecule on the surface of host cells is the primary binding site for both viruses. However, research has now shown that there are some significant differences in the manner in which these two types interact with CD4. Since the viruses bind to CD4 in preparation for penetration and infection of the host cell, several schemes for treatment of HIV infection focus on blocking the viral binding sites with soluble CD4, which can be prepared in large quantities by the techniques of recombinant DNA. Experiments in tissue culture show that when the binding sites of HIV-1 are blocked by soluble CD4, infectivity is inhibited. However, HIV-2 seems to be more resistant to inhibition by this technique. The amount of soluble CD4 that induces the same degree of inhibition is from 50 to 400 times greater for HIV-2 than for HIV-1. However, antibodies against CD4 on the host cell surface equally inhibit the binding of both types, suggesting that HIV-2 is not evading the inhibition by CD4 simply by binding to an alternate receptor. The HIV-2 type was consistently found to have greater infectivity, and binding analysis using radioactively labelled virus revealed that fewer HIV-2 particles were bound to target cells at saturation compared with HIV-1. Both the reason for these differences and their clinical implications remain uncertain. (Consumer Summary produced by Reliance Medical Information, Inc.)

AIDS research

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Clinical pharmacology of 3'-azido-2',3'-dideoxythymidine (zidovudine) and related dideoxynucleosides

Article Abstract:

The acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). HIV, a retrovirus, can be grown in the laboratory for testing drugs which might inhibit the growth of this deadly virus in humans. Drugs such as deoxynucleosides, which inhibit HIV from replicating, offer the best antiviral action. One of these medications, zidovudine (AZT), has been helpful in slowing down the disease process and prolonging life in patients with HIV infections. The effectiveness of zidovudine and related drugs is reviewed. It is likely that other medications in this compound group, each working in a different pathway, or a combination of drugs will offer improved outcomes for AIDS patients. Advanced methods of detecting optimal drug levels are being used to determine the most effective therapeutic doses.

Evaluation, Antiviral agents, Zidovudine, column

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