Magazine article Drug Topics

Dogging a Killer: Investigational AIDS Treatments

Magazine article Drug Topics

Dogging a Killer: Investigational AIDS Treatments

Article excerpt

Scientists are exploring a fantastic variety of strategies designed to intercept the AIDS virus. The approaches detailed here offer some insight into what's going on.

ANTIVIRALS

3TC, Glaxo Inc.: Currently in phase II/phase III studies, this nucleoside analog reverse transcriptase inhibitor interferes with the enzyme that HIV uses to duplicate its genetic material. An oral agent, it is being studied in patients over 12 years of age, both as a monotherapy and in combination with AZT (zidovudine or Retrovir, Burroughs Wellcome Co.) Glaxo expects to have an open- label protocol up and running shortly for people with no other treatment options. Patients are eligible for enrollment if they have a CD4+ count of 300/mm sup 3 or less, if they are not eligible for formal studies of 3TC, and if they are intolerant or resistant to other therapies.

5A8, Biogen Inc.: 5A8 is a monoclonal antibody currently in preclinical trials. It is designed to latch onto the CD4+ portion of uninfected cells, thus blocking HIV's entrance into those cells.

935U83, Burroughs Wellcome CO.: This compound is an oral nucleoside analog reverse transcriptase inhibitor. Currently in phase I, it is being studied in combination with other antiretrovirals.

Alvircept sudotox or sCD4-PE40, The Upjohn Co. and the National Institutes of Health: The compound, which was discovered by NIH scientists, appears to be effective against both HIV-1 and HIV-2. The soluable CD4 ("sCD4") portion of the molecule binds selectively to cells that display gp- 120, an HIV protein that appears on the surface of commandeered cells at some point in the infection process. Then, PE40, a toxin, destroys them. Alvircept is not designed to destroy all infected cells. An intravenous agent, it is being used as monotherapy in phase II trials. Patients are make and female adults with CD4+ counts between zero and 500/mm sup 3 .

Atevirdine mesylate or U-87201E, Upjohn: An oral compound, atevirdine is now in phase II trials. It is a nonnucleoside reverse transcriptase inhibitor specific to HIV-1. Present studies are investigating the agent's usefulness as monotherapy and in combination with standard nucleoside reverse transcriptase inhibitors. Trial participants are adult males and females with CD4+ counts ranging from 100/mm sup 3 to 500/mm sup 3 . Future studies will examine the compound's effectiveness in patients with CD4+ counts between zero and 500/mm sup 3 .

AZT-P-ddI (Scriptene), Baker-Norton Pharmaceuticals Inc.: The company describes the compound as a patented new molecule that links AZT and ddI together. Early clinical trials are now getting under way.

Curdlan sulfate, Lenti-Chemico Pharmaceutical (a subsidiary of Japan's Ajinomoto Co.): Produced from a mushroom extract, curdlan sulfate is an intravenously administered agent now in phase I studies. In vitro studies suggest that the compound prevents HIV from attaching to CD4+ cells. Scientists analyzing the results of the first small human trial were surprised to discover an apparent post-therapy increase in CD4+ count. The observation will receive much attention in upcoming trials.

d4T (stavudine or Zerit), Bristol-Myers Squibb Co.: Like BMS' ddI (didanosine or Videx), d4T is a nucleoside analog and reverse transcriptase inhibitor. An oral compound, it is in phase II/phase III clinical studies in adults or children who have had prior exposure to AZT. In addition, more than 8,000 patients who cannot use AZT or ddI have been enrolled in ongoing parallel track studies. The company is hoping to file a New Drug Application for the use of d4T as monotherapy before the year is out. Studies exploring its use in combination with ddI are in the planning stages.

Delavirdine mesylate or U-90152S, Upjohn: Currently in phase II, the oral agent is a nonnucleoside reverse transcriptase inhibitor. It is active against HIV-1, but not HIV-2. The company is studying the compound as monotherapy and in combination with nucleoside analog reverse transcriptase inhibitors in male and female adults. …

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