Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data

Article Abstract:

Patients with acquired immunodeficiency syndrome (AIDS) are are extremely susceptible to viral infections. Lately, patients are being infected with a strain of herpes simplex virus (HSV) that is showing resistance to treatment with the antiviral agent acyclovir. Clinical activation of acyclovir requires the formation of acyclovir monophosphate, a reaction catalyzed by the virus-specified enzyme thymidine kinase (TK). After triphosphorylation by cellular enzymes occurs, the drug can effectively inhibit the formation of viral DNA. The principal basis for acyclovir resistance in HSV is decreased activity of TK, resulting in the inability of the drug to inhibit viral replication. To be effective in these instances, alternative drugs must either be effective without the requirement for phosphorylation or be actively phosphorylated by cellular enzymes. Foscarnet meets the first criterion and vidarabine meets the second. The effectiveness of these drugs was recently examined in 26 patients with severe mucocutaneous HSV lesions who were variously unresponsive to intensive oral, parenteral or continuous infusions of acyclovir therapy. Favorable clinical response, in the form of the formation of new tissue where the lesions had been, was noted in 19 of 22 patients fully treated with foscarnet. This response is in significant contrast to the failure of acyclovir in the patients of this group. The lack of a satisfactory response in 10 patients who received a vidarabine course of treatment was contrary to previous evidence. There are some significant adverse effects that occur with foscarnet alone or in combination with other drugs. The data indicate that foscarnet therapy is an effective treatment for acyclovir resistant mucocutaneous HSV. Appropriate dosage schedules and other drug combinations and interactions require further study. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Physiological aspects, Drug resistance in microorganisms, Microbial drug resistance, Acyclovir, Herpes simplex virus, Herpes simplex, Vidarabine

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In vivo additive antiretroviral effect of combined zidovudine and foscarnet therapy for human immunodeficiency virus infection (ACTG protocol 053)

Article Abstract:

In some cases, using two drugs to treat an infection or a disease can be more advantageous than using only one drug. This is called combination drug therapy. One advantage of this method of treatment is that the dose of each drug can usually be reduced. This is important when the drugs being used have toxic side effects because using a lower dose of each drug will reduce side effects and toxicity. In addition, microorganisms are less likely to become resistant to drug treatment when two drugs are used simultaneously. Zidovudine (also called AZT) was the first drug that was shown to be effective in treating patients infected with the human immunodeficiency virus (HIV, which causes AIDS). However, recent studies have reported that the beneficial effects of zidovudine are limited, and that HIV may become resistant to zidovudine when it is used over long periods of time. Studies performed on cells grown in culture have shown that a combination of zidovudine and the drug foscarnet is more effective in killing HIV than either drug when used alone. Therefore, a study was performed to evaluate the effectiveness of combined therapy with zidovudine and foscarnet in six patients with HIV infection. The patients received treatment with zidovudine for 9 to 27 weeks prior to the beginning of the study. They received both zidovudine and foscarnet for two weeks, and were given zidovudine alone for the next six months. During the two-week period when both drugs were used, half the patients improved. However, 4 to 14 weeks later the beneficial effects of the combined treatment had disappeared. In treating HIV infections, it is possible that long-term treatment with both drugs will be required to maintain the beneficial effects of combination therapy. (Consumer Summary produced by Reliance Medical Information, Inc.)

Evaluation, HIV infection, HIV infections, Zidovudine, Drug therapy, Combination, Combination drug therapy

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Dapsone as a single agent is suboptimal therapy for Pneumocystis carinii pneumonia

Article Abstract:

Individuals with AIDS often develop pneumonia caused by Pneumocystis carinii. The pneumonia is most commonly treated with either high doses of trimethoprim-sulfamethoxazole or pentamidine. However, because both therapies may cause toxic side effects, other treatments are needed. The effectiveness of the drug dapsone (diaminodiphenylsulfone) was evaluated as a single treatment for pneumocystis pneumonia in patients with AIDS. Although the drug did not cause any adverse effects, it was not very effective, successfully treating only 61 percent of 18 patients. Studies have suggested that a higher dose of dapsone may be more effective, specifically 200 milligrams per day instead of the previous dose of 100 milligrams per day. Seven AIDS patients with mild cases of pneumocystis pneumonia were treated with 200 milligrams of dapsone daily. On the fifth day of treatment, two patients suffered respiratory failure and died. Four others experienced major adverse effects, such as difficulty breathing, kidney problems, internal bleeding, anemia and high fever. The study was ended prematurely because of the toxic reactions and lack of evidence of effective treatment for pneumocystis pneumonia. Patients had received 5 to 14 days of treatment with dapsone. These findings demonstrate that dapsone, administered as a single agent in high doses, is not effective and should not be used to treat Pneumocystis carinii pneumonia in patients with AIDS. (Consumer Summary produced by Reliance Medical Information, Inc.)

Complications and side effects, Pneumocystis carinii pneumonia, Dosage and administration, AIDS (Disease), Dapsone

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