TreatmentUpdate40: February 1993
Sean Hosein

In another study in the USA, various doses of oral d4T were given to 41 people with HIV infection to assess the drug's toxicity and effects on the immune system of people with HIV infection. Although the drug was given to 41 subjects with ARC or AIDS, data on only 36 subjects were made available. It is clear that doses of d4T greater than 1 mg/kg of body weight/day can be toxic to humans. Symptoms of this toxicity included pains in the hands/feet (peripheral neuropathy, PN), a severe shortage of red bloodcells which required transfusions, and increased levels of liver enzymes suggesting liver toxicity. In this preliminary report, none of the following symptoms were reported; painful inflammation of the pancreas gland (pancreatitis), diarrhea, reduced levels of white blood cells, low levels of platelets or disturbances in thinking.

BENEFITS?

At a dose of 1/2 mg/kg twice daily subjects have not developed PN while taking the drug for 6 months. Twenty subjects had increases of over 50 CD4+ cells within the first six months of the study. At the start of the trial half of the subjects had a CD4+count of approximately 200 cells. Six months later the equivalent figure was approximately 400 cells. Twenty-one subjects gained at least 2 kg over the course of the study. Many subjects reported reductions in symptoms such as diarrhea, fever, night sweats and fatigue. Indirect measures of viral replication suggested that viral activity may have been reduced as a result of taking d4T. Results from laboratory experiments suggest that taking AZT and d4T together do not result in increased anti-viral activity. This is because these drugs must first be converted into their anti-viral form, and this does not happen efficiently when both drugs are used together.

OVERALL EFFECT

Bristol-Myers Squibb Co. is conducting most of the experiments with d4T. The corporation has suggested that d4T "may offer palliation of HIV-1 infection." The key word is palliation; this means that the drug may relieve some symptoms but does not affect the overall course of the disease. Readers should note that similar, promising results were also reported from the phase I/II trials of ddI. However, results from controlled clinical trials (see TreatmentUpdate 39) suggest that ddI, compared to AZT, has no significant impact on survival even though it may temporarily raise CD4+ cell counts in some subjects.

REFERENCES:

1. Brown MJ, Mayer KG, Chafee SBD, et al. 2',3'-didehydro-3'de- oxythymidine (d4T) in patients with AIDS or AIDS-related complex:a phase I trial. Journal of Infectious Diseases 1993;167:21-29.

2. Ho H-T and Hitchcock MJM. Cellular pharmacology of 2',3'dide- oxy-2'3'- didehydrothymidine, a nucleoside analog active against human immunodeficiency virus. Antimicrobial Agents and Chemotherapy 1989;33(6):844-849.

3. Balzarini J, Herdewijn P, and De Clerk E. Differential patterns of intracellular metabolism of 2',3'-didehydro-2',3'dideoxythymidine and 3'- Azido-2',3'-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. Biological Chemistry 1989;264(11):6127-6133.

4. Shepp DH and Ashraf A. Effect of Didanosine on human inununodeficiency virus viremia and antigenemia in patients with advanced disease:correlation with clinical response. Journal of Infectious Diseases 1993;167:30-35.

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Copyright © 1993 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca