The AIDS virus becomes resistant to many members of a promising class of drugs if it is exposed to just one of them, according to a study that offers new evidence of just how slippery a foe the human immunodeficiency virus is.
The study involved protease inhibitors, which are experimental drugs designed to stop HIV from reproducing by disabling a crucial enzyme.
Researchers said the finding suggests that treating a patient with one protease inhibitor may make using another one later less effective and that using several protease inhibitors at once may not avoid resistance either. Other experts said it’s too soon to draw conclusions about what the findings mean for therapy.
The work is reported in today’s issue of the journal Nature by Jon Condra and colleagues at the Merck Research Laboratories of West Point, Pa., and scientists elsewhere.
The work involved a Merck drug called MK-639, and Condra stressed in a telephone interview that the results do not question the usefulness of that drug or of other protease inhibitors.
Patients appear to be benefiting from MK-639 despite the development of resistance, and Merck is developing the drug very aggressively, he said.
The results do suggest that if researchers want to test combinations of protease inhibitors, they should keep in mind that one drug in the mix might create resistance to the others, he said.
The study found that in four AIDS patients receiving MK-639, the AIDS virus spawned variants that showed varying degrees of resistance to MK639 and all five other protease inhibitors tested. Resistance was measured in test tubes by noting how much drug was needed to suppress virus reproduction.
In one patient, resistant variants appeared after 24 weeks of therapy. Other patients showed them at 44 and 52 weeks.
Condra said the results do not mean that the variants would show resistance to all protease inhibitors. He also said nobody knows what percentage of patients treated with MK-639 develop resistance to multiple drugs.
Condra said the study was done with patients who took a lower dose than current studies use. Higher doses may delay the appearance of resistant variants, he said.
Dr. Robert Schooley of the University of Colorado said it is not known whether drugs other than MK-639 would have the same effect. He also said using a combination of drugs may delay the development of resistance.