U.S. officials to tout new treatment policy

By Laurie Garrett

Newsday 17 Jan. '01

U.S. officials will announce a significant change in treatment guidelines for HIV disease when top AIDS scientists gather for their annual meeting next month.

Instead of telling American physicians to "hit early, hit hard," a policy in effect since 1996 that calls for giving HIV-positive patients powerful drug cocktails before the patients actually experience any symptoms of illness, the new National Institutes of Health guidelines will call for caution and delay in treatment.

The shift, NIH scientists will explain at the annual Conference on Human Retroviruses in Chicago, is prompted by an emerging consensus on three factors. First, the cocktails-called highly active anti- retroviral therapy, or HAART-can't wipe out all the viruses in a person's body, so patients must take these drugs every day, probably for the rest of their lives. That prompts the second and third factors: toxicity and resistance. The longer people take the HAART cocktails, the greater the number of side effects they experience. And there is greater the likelihood that the efficacy of the drugs will diminish, as drug-resistant forms of HIV swarm into a patient's bloodstream.

In practical terms, the new guidelines say physicians should hold off on using HAART until a patient's vital CD4 immune system cell count drops below 350 per milliliter of blood; guidelines now in use set a level of 500. A healthy, uninfected individual has a CD4 count of more than 800.

In terms of viral levels, the soon-to-be-replaced guidelines say patients should go on HAART when tests show 10,000 HIVs per milliliter of blood. The new guidelines call for waiting until the viral load tops 30,000 (as detected with branch DNA analysis) per milliliter of blood.

In a speech to the Royal Society of Medicine in London last month, prominent AIDS physician Charles Carpenter of Brown University, a member of the AIDS advisory committee to the NIH, signaled plans to change the treatment guidelines. "In retrospect," he said, "we now realize the risk of drug toxicity is greatly enhanced by taking these drugs early."

Yesterday, in an interview with Newsday, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, confirmed details of the new guidelines.

"It's clear we're not going to eradicate the virus with the drugs we have now," Fauci said. "And we're starting to see a greater and greater realization of the accumulation of toxic side effects."

Among the most troubling side effects seen in people taking the HAART cocktails are death of hip bone tissue, increase in blood cholesterol levels, neuropathy or loss of nerve sensations, kidney failure, radical alterations of liver metabolism, diabetes, skin rashes, pancreas failure, severe anemia, liver dysfunctions so acute as to require transplants and near-instantaneous death due to buildup of lactic acid.

Mark Harrington, leader of the activist Treatment Action Group in Manhattan, was infected 11 years ago. He held off on taking any drugs until 1996, when his CD4 count hit a low of 150. In retrospect, Harrington thinks he made the right decision because, unlike so many of his HIV-positive friends, he has been able to stay on the same drug cocktail for five years without witnessing emergence of drug-resistant strains.

Since starting the drug regimen, "I have had two kidney stone episodes" that required hospitalization, "one serious case of peripheral neuropathy, one chemical hepatitis bout, some nasty fat redistribution and a host of minor problems. And I'm lucky."

Dr. Michael Saag handles hundreds of HIV-positive patients in his clinic at the University of Alabama in Birmingham. He's worried about the rising tide of drug toxicities he sees, coupled with a change in patients' attitudes.

"I've got a lot of patients coming to me after three or four years on HAART saying, 'I just can't take it anymore,' or 'I'm tired of taking all these pills.' I think we need to keep in mind that this is a marathon, not a sprint."

Saag tells his patients that once they commence HAART, they must be prepared to live with the drugs for 20 or 30 years, or even longer. And there will be complications. He calculates that among typical, nonsmoking 35-year-old males, the odds they will have serious hypertension by age 45 are about six out of 100. But for a nonsmoking man on HAART the odds of serious hypertension by age 45 more than double to 16 per 100, largely because one group of the anti-HIV drugs boosts cholesterol counts.

New research indicates that completely effective HAART would take 70 years to kill off all HIVs in a patient's body. And few patients experience such effectiveness. Most are overcome by drug-resistant forms of the virus.

The ranks of such patients have swelled, and the FDA is considering weakening drug-testing requirements in an effort to speed more agents onto the roster of HAART drugs. That makes activists like Harrington and Gregg Gonsalves, policy analyst for Gay Men's Health Crisis in New York City, angry.

"I would argue that the drug companies and the Food and Drug Administration have been negligent, retrospectively, in not conducting or requiring long- term studies of the effects of these drugs so we can answer basic questions like these about their use," Gonsalves said. "Thousands of patients like me don't have the data to make an informed decision about when to use these agents, and the drug companies are laughing all the way to the bank."

Saag, however, feels optimistic. He is hopeful that within three to four years the details of these toxicities, and their biological causes, will be elucidated. And that, he hopes, will lead to much-needed improvements in drug therapy.