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Being Alive
MEDICAL UPDATE: AZT Resistance Revisited
Mark Katz, MD and reported by Jim Stoecker
June 5, 1993
Being Alive 1993 Jun 5: 4

Researchers in the New England Journal of Medicine recently reported the case of a young man who soon after initial infection with HIV, had rapidly falling CD4, despite AZT therapy. They soon found that the virus from the initial infection was, in fact, resistant to AZT. When the man was switched to ddI, his CD4 began to improve.

Resistance usually occurs after long term AZT use. If such an infected person infects someone else, he or she may pass on a strain of the virus that is AZT resistant. That is apparently what happened in the case noted above.

Back in 1987 when AZT began to be widely used, physicians assumed that someone on AZT would remain on the drug indefinitely. There was no reason to assume otherwise. As time went on, however, physicians saw that AZT began to lose its ability to forestall CD4 drop. We then began to look at the question of the virus developing a resistance to the drug.

Now we know that most people, after long term use, will develop some degree or other of AZT resistance. We know from various studies that a person is more likely to become resistant if the CD4 is low when AZT is first used. Researchers estimate that if AZT is started when CD4 is under 100, 87% will develop resistance within twelve months. In contrast, if AZT therapy begins when CD4 is greater than 500, only about 30% develop resistance after one year.

How do we know someone is AZT resistant? Unfortunately, we don't have an available test that can look at an individual's viral strains and determine if any strains are resistant to AZT. Physicians must use their clinical judgment. If a person on AZT develops an opportunistic infection or experiences the return of symptoms that disappeared with AZT use, resistance can probably be assumed. And if CD4 begins to fall after a time on AZT, resistance can be suspected.

What to do if AZT resistant? In the past, physicians just took the patient off the drug. Now we know that if the patient is tolerant of AZT, the best course is to stay on AZT and add another antiviral such as ddI or ddC. The current thinking is that there are multiple strains of HIV and an infected individual may harbor any number of different strains. Some may be AZT resistant, while others are not.

The important thing to remember is that resistance does not mean toxicity. It does not mean that AZT is hurting you. Rather, for the resistant person, the drug has to some degree lost its effectiveness, and should be supplemented.