NOVEMBER 11, 1994 GAY PEOPLE'S CHRONICLE 13

HEALTH WATCH

Understanding the alphabet soup of anti-HIV drugs

by John Carey, M.D.

AZT, ddl, ddC, d4T. What is this alphabet soup and how can a person with HIV know what, if anything, they should take to combat the virus?

First a little background. The human immunodeficiency virus (HIV) belongs to a group of viruses, called retroviruses, that have been around for millions of years. These viruses can cause disease in people and other animals. Retro means backward, and what is backward about this virus is how it stores genetic information. People store their genetic information in the form of DNA. When your body wants to make something from this information the DNA goes to RNA and then to proteins. These viruses store their genetic information in the form of RNA, which then goes back to DNA and from there to RNA again and then to proteins. The backward step going from RNA to DNA is what makes these viruses unique.

To make the backward step happen requires the action of an enzyme called reverse transcriptase. Because this is a step that only occurs in this virus, this was a natural place to try to interrupt the virus.

The first group of compounds that inhibit the growth of the virus at the level of the everse transcriptase enzyme are the alphabet soup group, AZT, ddl, ddC, and d4T. These are the compounds that are available by prescription.

Now before these drugs were approved by the FDA for use in people with HIV infection, they had to be tested in a series of clinical trials. The result of these trials has given us the information that helps people with HIV and provides their doctors with the information they need to use these drugs. These trials have been going on for a number of years and involve lots of people with HIV

infection, some with lots of t4 cells (helper t cells) and some with people with few t4 cells. The first trial compared AZT to a placebo sugar pills-in people who were recovering from their first bout with pneumocystis carinni pneumonia. In this group of people, AZT helped them gain weight, and their symptoms of HIV infection, fever, fatigue and occurrence of infections decreased. The people who took the AZT also lived longer on average then did the people on the placebo.

The next big trials of AZT asked if people with more T-cells could also benefit from AZT therapy. The results of these trials showed that people with fewer than 500 T4 cells had fewer infections if they took AZT than if they didn't. These trials also showed that if you had no symptoms from HIV infection, then the benefit from taking AZT was equal to the likelihood that you would develop side effects from the AZT.

The next trials, which also involved people with between 200 to 500 T4 cells, asked if the benefit in terms of preventing development of infections meant that people taking AZT lived longer. The two trials done showed that people with more than 200 T4 cells taking AZT had fewer infections. But they didn't live any longer than if they had waited until the T4 cells were down to 200 to take the drug.

Why is this? We think that it relates to the fact that after a while the HIV virus mutates so that AZT doesn't stop it from growing. The length of time that this takes seems to vary from person to person, but may be as short as six months in someone who has AIDS when they start taking medication, to several years if they start taking the medication when they have a lot of T4 cells and no symptoms.

Well, what to do if you have already been

on AZT for a while? Another study showed that if you had been on AZT for more than four months, you were better off if you switched to ddl. Other studies have shown that AZT was better than ddl for people who had never taken any anti-HIV drugs. What about people who can't tolerate AZT? A study compared ddl to ddC. In this group of patients and showed that there was no difference in these two drugs.

So, what is a person to do? The current recommendations leave a lot of room for people with HIV and their doctors to individualize therapy. These recommendations

are:

For people with more than 500 T4 cells: No studies to date have shown that the available drugs help people. Some studies coming in the future will look at combinations of drugs in this group.

■ For people with 200 to 500 T4 cells who do not have any symptoms: It is up to you and your doctor to decide if taking medication would be helpful.

For people with 200 to 500 T4 cells who have symptoms related to HIV infection: A trial of AZT is suggested. Combination

therapy with AZT plus either ddl or ddC may also be tried although there have been no trials that have shown combination therapy to be effective.

For people with fewer than 200 T4 cells: AZT is suggested.

For people who cannot tolerate AZT: ddl or ddC is suggested.

■ For people who have been on AZT and are tolerating it: If their 4 cells are stable and greater than 300, continue on AZT. For those whose T4 cell counts are falling, then switching to ddl or continuing on AZT is suggested. ■d4T is suggested for those who cannot tolerate ddl or ddC.

These are just general recommendations and there are many reasons why they may not apply to you. The best thing to do is have a frank discussion with your doctor about what any therapy can do for you and what are the likely consequences, good and bad. ✓

John Carey has cared for people with AIDS since 1983. He is the medical director of the Special Immunology Unit at University Hospitals of Cleveland, an outpatient unit for people with HIV/AIDS.

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