The goal of taking drug “cocktails,” or combination therapy, with AZT, 3TC, protease inhibitors and other medications to combat HIV infection is to keep the AIDS virus from replicating in your system, said Dr. Eric Rosenberg, an AIDS specialist and associate director of clinical microbiology at Massachusetts General Hospital.
Within an hour or so of taking the drug, blood levels of the drug rise, which keeps the virus from replicating. But several hours after that – the interval varies depending on the particular drug – levels of the drug in the system begin to fall, which allows the virus to begin replicating. When the virus replicates in the presence of sub-therapeutic levels of the drug, the virus is wily enough to mutate so that it can survive in this low-drug environment. The new viruses thus produced now carry the ability to survive, even when levels of the drug are increased again. Missing just one dose usually doesn’t lead to a resistant strain emerging, Rosenberg said, though it’s possible.
“So long as the virus can’t replicate, it can’t mutate and resistance to a drug does not develop, or at least develops as a much, much slower rate,” said Rosenberg.
Dr. Clyde Crumpacker, director of virology at Beth Israel Deaconess Medical Center, noted that it has taken years for doctors to appreciate the implications of all this – specifically, that the best way to keep the AIDS virus from replicating is to hit it hard with multiple drugs all at once, rather than waiting until a patient became resistant to one drug before starting another. “This is something the developing world can learn from the American experience,” he said. “Americans had to learn it the hard way. Other countries can benefit from this.”