By Robin Eisner 31 January 2001

"Hitting early, and hitting hard" with the AIDS cocktail is no longer the best approach for HIV-infected people, the government says, because side effects, such as high cholesterol and liver problems, outweigh any benefits of treatment.

Five years ago, Time magazine named AIDS researcher David Ho "Man of the Year" for his idea that new AIDS drug "cocktail" might eliminate the virus and potentially cure both very sick AIDS patients and those who had been infected with HIV.

Doctors, AIDS activists, the pharmaceutical companies all jumped on the bandwagon touting these drugs for AIDS patients, and for the tens of thousands of people infected with HIV but not yet showing signs of the devastating related infections, such as pneumonia. So with this "hit early, hit hard," approach, physicians began to prescribe the combination therapy of drugs to relatively healthy HIV- infected people. The drug mixture included the newly approved anti- HIV protease inhibitor drugs and the old standbys, like AZT.

Fast-forward to 2001: For AIDS patients, the drugs have been a godsend, reducing the number of deaths each year by 50 percent. For HIV-infected people, though, the promise has not lived up to the reality. At a conference next week on human retroviruses in Chicago, the federal government will now say infected people should wait for awhile before they begin to take these powerful drugs, citing dangerous side effects and drug resistance outweighing any benefits of treatment.

The announcement comes as another blow for the AIDS community, which is starting to see an increase in infection rates in San Francisco and New York City. Forty-seven million people worldwide have been infected with HIV since the beginning of the epidemic 15 years ago, with 2 million dying each year. Some 311,000 Americans currently have AIDS; another 120,000 are infected with HIV. Vaccines remain in development.

More Conservative Treatment Approach

"We are now being a little more conservative in treatment," the director of the National Institute of Allergy and Infectious Diseases Dr. Anthony Fauci told NIAIDS is a federal agency that helps set AIDS policy in this country. "Although the therapy is beneficial, it is better later in the course of infection."

While people with more advanced AIDS might more willing to face the side effects of the drugs rather than the devastating AIDS-related conditions - such as infections, wasting and lymphoma - less ill people can delay their potential exposure to side effects. To stay healthy, people probably need to take the medications, which are expensive and require following a rigorous regimen, for the rest of their lives.

Side effects of the drugs include unusual body fat redistribution, high cholesterol levels, sugar metabolism problems, hip bone tissue death, kidney failure, liver metabolism alterations and loss of nerve sensations.

"I have had to change drugs a few times," says Michael Harrington, senior policy director for the Treatment Action Group, an organization founded in 1992 dedicated to advocating for larger and more efficient AIDS research efforts. He experienced kidney stones twice, high cholesterol and liver and peripheral nerve problems.

Resistance Problems

Many patients also fail to properly take what can amount to a dozen pills in some treatment plans, a practice that can lead to drug resistance to the virus. During the time of a missed dose, a mutant virus can grow within the person's body that no longer responds to medication.

"I take a dozen pills a day," explains Greg Gonsalves, director of treatment advocacy for the Gay Men's Health Crisis, a group founded in 1981 dedicated to treatment of New Yorkers with AIDS. "It's a rigorous process. You have to take some with food and some without. It is not a trivial task to take these drugs."

Treatment With a Theory, Not Data

The drugs had been prescribed despite the fact that there is no long- term clinical testing showing at what point during HIV infection they could help. The doctors made their recommendations based on the success of using the drugs with a small group of patients who had developed AIDS.

"In 1996, we had no data that hitting hard was either bad or good," says David Barr, director of the Forum for Collaborative HIV research. "The general approach to infectious diseases was that the sooner you get rid of them the better to eliminate infection?"

"There was excitement from everyone, from doctors, from the drug companies from the AIDS community," Barr adds. "Everyone got on the train."

The hoopla has, indeed, paid off for those with more serious disease. "Even in advanced disease, people now are able to go back to work," says Dr. Oren Cohen, assistant director of medicine at NIAID. "There have been very dramatic changes with these drugs. We shouldn't lose sight of this."

"I would much rather be dealing with side effects of these medications than patients dying," says Dr. Robert Schooley, head of infectious diseases at the University of Colorado Health Sciences Center and chair of the Adult AIDS Clinical Trials Group, an international group of investigators studying AIDS treatments. Referring to the policy change, Schooley says: "It won't be the last time the pendulum swings in AIDS treatment. It is a constantly evolving target."

Unlike antibiotics that can eliminate bacteria from people, research has shown that high levels and early dispensing of these drugs cannot eradicate the virus in HIV-infected individuals.

The new guidelines will suggest that HIV-infected people should delay starting the cocktail until their CD4 immune cell count falls below 350; the current recommendations say people might consider the cocktail at 500 CD4 cells or less. CD4 cells decrease as infection proceeds to AIDS. Healthy individuals have around 800 to 1,300 cells.

Activists: Time to Test When To Use Drugs

Since no clinical trials have been done to determine when is the best time to take the cocktail of AIDS drugs, AIDS activists are calling on the government to begin doing so.

"This is one of the most important questions in AIDS research," says Treatment Action Group's Harrington. "I am angry and disappointed they didn't do such a study. They are more interested in a high tech treatment or a new drug, not in answering questions important to the public and to people with HIV."

NIAID's Fauci says such a study would be "logistically impossible" to do, because of the complexity of the different treatments in the United States. "No one has yet been able to come up with a protocol," Fauci says.

Doctors are urging caution for those HIV-infected people who started the cocktail a few years ago and may wonder whether they should stop taking the medications.

Talk to Doctor Before Stopping Drugs

NIAID's Cohen says patients should talk to their doctors about how to proceed. "If the decision is to discontinue treatment," Cohen says, "the patient should be monitored very carefully."

While AIDS activists are used to changes in AIDS treatments, infected people may still get upset about the new policy. "Some people will be confused, some will be mad, yet others will be relieved that they can wait longer," Gonsalves says.

Barr says those people who may have died or who have developed drug resistance because they took the drugs early saddens him. "Had they waited," Barr says. "They might still be OK."