AIDS Committee of Windsor: HIV Treatment Information

d4T (stavudine, Zerit) is an antiretroviral drug approved for people with advanced HIV infection who are failing other drugs in its class (e.g. AZT, ddI, ddC and 3TC) for any reason. However, standard of care has evolved substantially since the original approval of d4T and today the most common use of the drug is to serve as an alternative to AZT as part of a three-drug combination therapy regimen which includes either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).

d4T is a nucleoside analogue, which means that it works by obstructing the building blocks of genetic material (e.g. RNA or DNA) from being assembled together and therefore inhibits the virus from reproducing. Although d4T appears to impair HIV's ability to replicate, it will never be a cure for AIDS since it does not totally eradicate HIV from the body.

Pregnant Women and Children
d4T has not been formally studied in pregnant women. It does cause fetal damage in laboratory animals, but it is unclear if the same effect is seen in humans. Women should be cautious of breast-feeding while taking d4T because it may be passed through breast milk resulting in potential toxicity to the child.

HIV and the Brain
Because HIV can infect brain cells, it's important to consider a drug's ability to reach the brain when putting together an anti-HIV regimen. It's probably wise to include at least one drug that has been shown to cross the blood-brain barrier to some useful degree as part of your regimen. These include AZT (zidovudine, Retrovir), d4T (stavudine, Zerit), abacavir (Ziagen), nevirapine (Viramune), amprenavir (Agenerase) and to a lesser degree indinavir (Crixivan) and 3TC (lamivudine, Epivir). Efavirenz (Sustiva) has not been shown to cross the barrier to a significant degree, but some experts speculate that it might have some useful effect in impacting HIV in the spinal fluid.

What About Side Effects?
The major side effect of d4T is peripheral neuropathy, pain or tingling in feet and/or hands (experienced by 15-21% of people enrolled in studies). In many but not all cases, the symptoms are resolved after the drug is stopped. Early signs of peripheral neuropathy could be a burning sensation, tingling or numbness in the fingers or toes, or in some cases a deep soreness or shooting pains which may be transient but always affect the same spot on the legs or feet. If you think you may be having sensations of peripheral neuropathy, consult your health care provider about possibly switching to another therapy.

Pancreatitis, a serious inflammation of the pancreas, has been reported in about 1% of people taking d4T but it is not clear that the problem is caused by the drug. Similar rates of pancreatitis are seen with almost all other drugs of this class, including AZT, and may simply reflect an underlying disease process related to HIV. It is still not known whether prolonged use of d4T or use of d4T in combination with other therapies may increase the risk of developing pancreatitis. In other studies, alcohol use appears to increase the risk of pancreatitis.

People with a history of liver problems should monitor their liver function tests closely while taking d4T or any other drug of this type. Although no formal drug interaction studies have been done, caution should be exercised in taking d4T at the same time as other treatments that impair liver function.

d4T may also cause some degree of bone marrow suppression, interfering with the production of a type of white blood cell called granulocytes. This condition (granulocytopenia) occurs rarely, and much less frequently with d4T than with AZT. Other less commonly reported side effects of d4T include fungal infections of the skin, dry skin and neurological complications, such as insomnia.

How to Use It?

Dosing
Studies of d4T suggest that the optimum dose of the drug is 40mg twice a day (total daily dose of 80mg). However, an uncontrolled and loosely reported expanded access program showed that a 20mg twice a day dose (total daily dose of 40mg) was as effective as the higher dose and associated with significantly less peripheral neuropathy. d4T, administered orally, is available in four different dosages—40mg, 30mg, 20mg, and 15mg—and the recommended starting dose is based on body weight. Bristol-Myers Squibb recently released a new oral paediatric formulation of d4T for the treatment of children with HIV. The oral solution is a fruit-flavoured powder that when mixed with water supplies 200ml of a 1mg/ml solution.

Drug Interactions
There are a few drugs that have side effects of peripheral neuropathy that should only be used with caution in combination with d4T. Drugs such as amphotericin B (Fungizone), foscarnet (Foscavir), and dapsone may increase the risk of developing peripheral neuropathy. Ganciclovir (Cytovene) and intravenous pentamidine (Pentam) may increase the risk of pancreatitis. It is still unknown whether d4T used in combination with ddI or ddC will increase the risk of neuropathy and/or pancreatitis.

Food Interactions
d4T can be taken with or without food.

Where To Get It?
d4T is available through prescription at pharmacies and hospitals.

This information was provided by the Community AIDS Treatment Information Exchange (CATIE). For more information, contact CATIE at 1-800-263-1638.