TreatmentUpdate 67, Volume 8, No 3; April 1996
Sean Hosein

`Related' to AZT, d4T (Stavudine, Zerit) has recently been approved for the treatment of HIV/AIDS in the USA. In lab experiments, d4T shows anti-HIV activity, but is weaker than AZT. d4T does not have any significant anti-bacterial effects. Results from lab experiments suggest that using a combination of AZT and d4T results in weaker anti-HIV activity than when either drug is used alone. Combinations of d4T and ddI have greater anti-HIV effects than either drug used alone. This combination is currently being tested in HIV-infected humans.

Experiments in people

According to the manufacturer, d4T is well absorbed when taken with or without food. CD4+ cell counts begin to increase between the 4th and 8th week of use. Preliminary results from one study where AZT users were given either continued AZT or d4T 40 mg twice daily, show average increases of 30 to 50 cells in the CD4+ counts of subjects receiving d4T. Conversely, subjects on continued AZT had their CD4+ cell counts fall. This difference was statistically significant. After six months, the average CD4+ cell counts among subjects on d4T returned to their pre-study levels.

Effects on production of HIV

Production of HIV fell to 10% of pre-study levels in subjects who received at least 2 mg/kg/day of d4T. This suppression of viral production lasted for 6 months. This event was statistically significant. After the 6th month, production of HIV rose.

Summary

The drug d4T has anti-HIV activity when given to people with HIV/AIDS at a dose of 1 mg/kg of body weight per day. The side effects most commonly reported are damage to the nerves in the hands and feet. As well, symptom-free and non-life-threatening liver damage may occur. A study of a combination of d4T and ddI is underway. As with every other anti-HIV agent, some people will develop life-threatening infections/cancers. Results from a larger study in progress suggest that switching from AZT to d4T may be more beneficial than continuing with AZT. Results from lab experiments on combinations of d4T and other drugs appear in the next article.

Toxicity

The most common side effect of d4T use is damage to the nerves of the hands and feet. People have experienced pain and numbness called PN (peripheral neuropathy). PN can occur at any dose of d4T. However, it is more common at doses greater than 2 mg/kg of body weight/day. When PN develops and patients stop using the drug, recovery can take "between 1 week to several months." According to the manufacturer, "most people recover from PN when they stop taking d4T." After recovering from PN, patients may resume taking the drug, usually at half the original dose.

There have been cases of liver damage in users of d4T. This toxicity is revealed by increased levels of liver enzymes in the blood. The liver damage was not life threatening and most patients did not need to decrease their dose of d4T. Preliminary results from the ongoing study of d4T versus AZT indicate that roughly 10% of subjects in each group developed increased levels of liver enzymes in the blood. Subjects did not report any pain or other symptoms linked to the increased liver enzyme levels. Painful inflammation of the pancreas gland (pancreatitis) occurs in less than "1% of [d4T-treated patients]."

REFERENCES:

1. Riddler SA, Anderson RE and Mellors JW. Antiretroviral activity of stavudine (2',3'-didehydro-3'-doxythymidine, d4T). Antiviral Research 1995;27:189-203.

960401
CATE6702

Copyright © 1996 - 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