AZT is the most widely used and best known of all the antiretrovirals. In more than eight years of testing, its value has been confirmed repeatedly for people with AIDS. It has become the standard initial HIV treatment and, with the recent approval of other antivirals in combination with AZT, its effectiveness has been increased.

The benefit of AZT monotherapy has been demonstrated to diminish over time. Some people have shown resistance to the drug after six months of use, while others have benefited from AZT for longer than two years. The addition of 3TC in combination with AZT appears to delay the development of resistance significantly, and improves anti-HIV activity. People who begin AZT therapy early, while still asymptomatic, seem to tolerate the side effects of the drug better and benefit from the drug for a longer period of time².

There is evidence that AZT crosses the blood-brain barrier and has been shown to be helpful in managing HIV-related dementia in some people.

AZT sometimes causes temporary problems in the first weeks of use, causing some people to discontinue the drug prematurely. These initial effects include nausea, headaches, hypertension, and a general sense of feeling ill. These may be due to the drug itself or to the patient's anxiety about taking it. Physicians report that when patients are encouraged to bear with these problems, they subside in one to three weeks. For patients who have used AZT for long periods, there is some evidence of muscle weakness or damage, otherwise known as myopathy. Myopathy is also a side effect of HIV-disease, unrelated to AZT use. AZT-related myopathy can be distinguished from HIV-related myopathy through biopsy. Like other AZT side effects, AZT-related myopathy has been seen less frequently at the current standard dose.

AZT-related anemia and granulocytopenia (bone marrow suppression), the more serious side effects associated with AZT use, are reversible by lowering the dose of the drug, discontinuing use or managing side effects with therapy. 

Who Should Use It?

For people who have not been on any prior antiretroviral therapy:

• 200mg of AZT taken three times a day be used as first-line therapy, with the following refinements,
• people with 200-500 CD4+ cells and no symptoms should initiate of antiretroviral therapy or continue observation and monitoring until evidence of deterioration, at which time antiretroviral therapy should be started,
• those with 200-500 CD4+ cells and with symptoms should start antiretroviral therapy,
• combination therapy should also be considered although there is no clinical data to support this yet.

For people who have been on prior AZT therapy:

• people who are tolerating AZT therapy and have a stable CD4+ cell count above 300, should continue on AZT,
• those with <300 CD4+ cells should either continue on AZT or switch to ddI.

Consistent monitoring of bloodwork is recommended for people using AZT and extreme caution should be exercised in using AZT when there is evidence of bone marrow compromise.

Whatever one's condition, AZT should not be chosen—or rejected—solely out of anxiety or without consideration of all the possible risks and benefits.

Because AZT is primarily excreted through the kidneys, concurrent use of drugs which have kidney toxicities or which suppress red or white blood cells may increase the risk of side effects from AZT. Examples of these include dapsone, ganciclovir, rifabutin, clarithromycin, pentamidine, amphotericin B, flucytosine, vincristine, vinblastine, adriamycin and interferon. While use of these drugs may increase the likelihood of experiencing side effects of AZT, concurrent use of the drugs are not necessarily discouraged but should be monitored. Pharmacokinetic studies have shown that when AZT is used in combination with clarithromycin, the AZT levels in blood can be decreased by up to 50%. Similarly rifabutin can decrease AZT levels in blood when used in combination, however the AZT levels are still thought to be in the therapeutic range.

AZT is metabolized through the liver, therefore people with a history of liver problems want to monitor liver function carefully while on AZT. People with a history of injection drug use who are currently on drug therapy programs should be aware that morphine and other associated drugs such as levomethadon are also metabolized through the liver. 

AZT and Children
Positive mothers usually pass the antibodies for HIV to their newborns, so a baby will test positive on the antibody test whether it is positive or not, and both the p24 antigen test and PCR can miss HIV infection in children younger than 3 months. HIV+ mothers who are not on antivirals transmit the virus to their infants about 25% of the time.  AZT significantly reduced the rate of transmission: 8.3% of the women on AZT transmitted the virus to their infants compared to 25% of those on the placebo. As a result of these findings AZT has been approved to prevent transmission from mother to fetus.

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.

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