AIDS Drug Therapy Is Undergoing Shift
Federal health officials next week will propose reversing course on the prevailing “hit early/hit hard” approach to treatment of AIDS, responding to growing concerns that prolonged use of drug cocktails can cause potentially dangerous side effects and lead to drug resistance.
Officials will recommend that AIDS-infected individuals hold off starting the powerful drug cocktails until their immune systems show signs of deterioration. The change in thinking reflects the sobering conclusion that AIDS patients likely will require drug therapy for the rest of their lives and must balance their need for therapy against the possible side effects that often develop with long-term use.
The new recommendation, expected to be announced during a retrovirus meeting in Chicago that begins Monday, comes after years of debate within the medical profession and the AIDS community about the appropriate timing and dosage for the potent AIDS drug cocktails that debuted with such promise five years ago.
Patients and physicians long have been aware of the possible downside of starting any new AIDS drugs early. From 1987, when the earliest AIDS drug was introduced, the human immunodeficiency virus has demonstrated a clever and sinister ability to mutate and become drug-resistant.
Despite this, hope flared in the mid-1990s with the development of powerful new drugs that offered the promise of totally eradicating the virus from the body. Recent studies, however, have shown that the virus rebounds with a vengeance when therapy is stopped.
As a result, AIDS-infected individuals likely will be taking drugs indefinitely, possibly developing drug resistance as well as potentially serious side effects. These include unusual body fat redistribution, early heart disease, high cholesterol levels, sugar metabolism problems, hip bone tissue death, kidney failure, liver function changes and loss of nerve sensation.
“ ‘Hit hard’ still goes, but we are taking a more conservative approach as to when to start,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who helped write the new guidelines.
“We now know that eradicating the virus is not in the cards--and at the same time, we are seeing an increasing number of alarming side effects,” he added.
The panel, convened by the Department of Health and Human Services, will recommend that patients now wait until their critical immune system CD4 cell counts drop to 350 per cubic millimeter of blood from the current and relatively high 500 before starting the drugs. Normal is about 800 to 1,000.
The change comes as a blow to the AIDS community, which had pinned its hopes on these potent drug combinations and was buoyed by the startling drop in AIDS deaths nationwide. AIDS mortality began decreasing by as much as 50% annually after the drugs went into widespread use in 1996.
As with many diseases, the treatment of AIDS has evolved over time and likely will continue to do so. “It is a work in progress,” Fauci said.
The combination therapy, which was prescribed for relative healthy infected people, typically mixed the most recently developed protease inhibitor drugs with drugs from another category, nucleoside analogs. The idea was to target the virus at different points in its life cycle to halt its replication.
Indeed, the drugs were successful in substantially decreasing the amount of detectable virus in people’s bodies and in increasing CD4 levels. This resulted in keeping people alive longer and in improving the quality of their lives.
But the drugs, over time, have shown that they have limits.
The regimens are complicated and cumbersome, requiring as many as a dozen or more pills daily and involve rigorous schedules that can be difficult to follow. Some have to be taken with food, for example. Others must be taken on an empty stomach. If compliance falters, drug resistant strains of the virus can develop, making the drugs ineffective.
And--as is frequently the case with long-term drug use for many chronic conditions--patients can develop side effects, some serious.
“It’s a very confusing time,” said writer and AIDS activist Larry Kramer. “Some people do OK on drugs, but many [drugs] have too many side effects and long-range side effects. There is no doubt that drugs are only good for so many years--and so people are thinking: wait.”
Some AIDS experts are worried that the new treatment recommendation will prompt an overreaction from both patients and doctors--that patients will stop medication, even if they are doing well, or refuse to even start. And they noted that, regardless of the problems, the drugs continue to prolong life.
“There’s no question there are complications from these drugs, but I would rather deal with these side effects than dying,” said Dr. Robert T. Schooley, an AIDS specialist at the University of Colorado Health Sciences Center. “In 1994, before these drugs, one patient out of six in our clinic died. Today it’s one in 50.”
He and other AIDS researchers support the new policy. Nevertheless, they are concerned that patients--and those doctors less experienced in treating AIDS--not misinterpret it.
“We now have more experience with starting effective drug regimens later . . . and seeing the immune system recover over time,” Schooley said. “It appears that in many people we can wait a bit longer and get away with it.”
Still, many of his patients--having heard of the impending change and being frightened about side effects--are asking to quit.
One of his patients recently decided to stop taking the drugs, and the concentration of virus in her system increased more than a thousandfold and her CD4 cells dropped to less than half of what they had been while she was on the drugs, he said.
Also, the patient quickly developed several serious AIDS-related infections, Schooley said.
“Many people who stop therapy see a rapid rebound in viral replication, a decline in CD4 cells and the onset of symptoms,” Schooley said.
He said that current treatment should be a risk/benefit “balancing act,” tailored to the needs of each patient.
Fauci stressed that the changes do not apply to those already taking drugs and doing well on them.
“We’re not going to tell you to stop,” he said. “Keep doing what you’re doing.”
Scientists are working on developing newer AIDS drugs that will be more convenient and produce fewer side effects. If they are successful, then “the pendulum toward starting earlier could swing again,” Schooley said.
