Susceptibility to nucleoside analogues of zidovudine-resistant isolates of human immunodeficiency virus

Article Abstract:

The human immunodeficiency virus (HIV), which causes the acquired immunodeficiency syndrome (AIDS), can be suppressed by agents that inhibit the viral enzyme called reverse transcriptase; this enzyme is essential for the replication, or production, of the virus. One of the first reverse transcriptase inhibitors, zidovudine (AZT), was shown to suppress HIV infection and increase the survival time of patients with AIDS or AIDS-related complex (ARC). However, AZT causes myelosuppression, or inhibition of bone marrow function, and its widespread use has resulted in the development of AZT-resistant viral strains. Patients who were treated with AZT for six months or more had reduced susceptibility to the drug and chemically similar compounds with a 3'-azido group. But AZT-resistant strains of HIV were still vulnerable to nucleosides without the 3'-azido group, such as 2',3'-dideoxycytidine and 2',3'-dideoxyinosine. The specific resistance to compounds containing the 3'-azido group suggests that the gene which controls reverse transcriptase undergoes a specific mutation preventing the interaction of reverse transcriptase and 3'-azido nucleosides. The relationship between these genetic changes and clinical drug resistance has not been determined. Because of the gradual appearance of resistance and inconsistencies in the HIV disease course, it has been difficult to correlate the development of resistance with clinical factors. The combination of AZT with other agents which remain active against resistant strains may be effective in treating HIV infection without causing the development of drug-resistant HIV strains. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, HIV (Viruses), HIV, Drug resistance in microorganisms, Microbial drug resistance, Zidovudine

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Antiviral therapy and immunomodulators in patients with AIDS

Article Abstract:

The disease AIDS results from infection of the immune system by the retrovirus known as human immunodeficiency virus (HIV). Treatment of patients infected with HIV requires a three-tiered approach. Therapy must address the infections and diseases that result from poor immune functioning; it must work to control the HIV infection itself; and the immune system must be repaired. The third tier has proven to be the most difficult to address thus far, because most of the agents aimed at treating the complications of immunodeficiency or controlling HIV harm the immune system. These antiretroviral agents can cause leukopenia (decreased numbers of white blood cells, which help to fight infection), anemia (a decrease in red blood cells, which carry oxygen), and thrombocytopenia (a decrease in blood platelets, which are necessary for clotting). Growth factors, which are stimulating hormones, can be of use in alleviating some of the side effects caused by these anti-HIV drugs. Three potentially useful growth factors have been identified: G-CSF, GM-CSF, and erythropoietin. They are all involved in the development of blood cells; they stimulate the production of blood cells and affect on the proper functioning of mature cells as well. Studies have shown that in combination with AZT and interferon, two common drug treatments for HIV and HIV-related symptoms, these growth factors act as immunomodulators by alleviating the blood deficiencies normally associated with drug therapy. It is therefore suggested that growth factors are an important adjunct to treatment with antiviral agents in patients with HIV disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Physiological aspects, Growth factors, Antiviral agents, Biological response modifiers

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Similar abstracts:

• Abstracts: Pharmacodynamics of 2',3'-dideoxycytidine: an inhibitor of human immunodeficiency virus. Safety and tolerance of dideoxycytidine as a single agent: results of early-phase studies in patients with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex
• Abstracts: Alternating and intermittent regimens of zidovudine (3'-azido-3'-deoxythymidine) and dideoxycytidine (2',3'-dideoxycytidine) in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex
• Abstracts: Treatment of AIDS with combinations of antiretroviral agents. The challenge of combination antiretroviral therapy for AIDS: an introduction

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