HEAL Toronto: AIDS study could ease drug burden for patients

Health Education AIDS Liaison, Toronto

AIDS study could ease drug burden for patients

By ROD MICKLEBURGH
The Globe and Mail
Wednesday, November 28, 2001 – Print Edition, Page A1

VANCOUVER -- Findings by a team of Vancouver AIDS specialists may revolutionize future treatment of patients stricken with the disease, allowing them to delay high-cost, often debilitating drug-cocktail programs for as long as four years.

During the past year, the new treatment method has already enabled more than 1,000 British Columbia patients to come off the rigorous, expensive anti-AIDS drug regimen that is almost universally applied. The move created a saving of $4-million.

"We were the first in the world to consider whether we were starting treatment at the right time," said Dr. Michael O'Shaughnessy of the B.C. Centre for Excellence in HIV-AIDS at St. Paul's Hospital, who assisted in the study headed by the centre's Dr. Julio Montaner.

"Our findings are great news for patients and great news for health-care costs."
Results of the Vancouver study are published in today's edition of the influential Journal of the American Medical Association.

An accompanying editorial says the study, and a similar British paper published in the same edition, will have a profound effect on treating patients with the AIDS virus.

"These are very important papers," Dr. Roger Pomerantz, head of the infectious-diseases department at Jefferson Medical College in Philadelphia, said in the journal's editorial.

"I predict they will change therapy for all HIV-infected individuals in the developed world."

The treatment method under review is the so-called drug cocktail, a combination of a number of powerful antiretroviral pills taken daily by AIDS patients. Since its introduction in the mid-1990s, the prescription has seemingly stopped the disease in its tracks for the vast majority of those taking the medicine.

However, the drugs come with a cost. Averaging $12,000-$15,000 a year, they are enormously expensive, the daily regimen is difficult to follow for patients without a stable lifestyle, and they often cause serious side effects.

Now, the Vancouver study has found that antiretroviral therapy can begin much later than previously thought without losing medical effectiveness.

Dr. O'Shaughnessy said the CD4 cell count at which most patients generally begin taking the drugs can safely be lowered from about 500 to about 300. "That often takes three or four years. That's a long time to be off the drugs."

The team studied 1,219 AIDS patients receiving the drug cocktail over a three-year period ending in 1999. They found virtually no difference in health outcomes among patients with CD4 counts of 350-500 and those with CD4 counts of 200-350.

Glen Hillson, who has been living with the AIDS virus for 20 years and was at death's door when the cocktail treatment came along, said the findings are a real breakthrough for AIDS/HIV patients.

"Published treatment guidelines are being rewritten as we speak," said Mr. Hillson, board chairman of the B.C. Persons With AIDS Society. He takes seven antiretroviral pills a day, plus about 20 others to combat side effects.

"These drugs are not only debilitating. They can also be very dangerous. We've had 62 patients on the drug program suffer heart attacks," he said.

"There are also high incidences of liver failure, diabetes, osteoporosis and fat accumulation. It's very good news that not . . . [taking] these drugs will do more good than harm."

Mr. Hillson noted that the main health-research institute in the United States had proposed a massive, 10-year study to determine the best time to begin antiretroviral treatment.

"Then Julio [Dr. Montaner] does this little retrospective analysis and we are getting answers."

The JAMA editorial pointed out that almost everyone infected with HIV went on the three-drug anti-AIDS cocktail when it first became available.

Then, the side effects began showing up and AIDS specialist began to rethink.

From JAMA November 28, 2001

Predictors of Outcomes of Antiretroviral Therapy

Initiation of antiretroviral therapy for patients with chronic, asymptomatic HIV infection is generally based on CD4 cell counts and plasma HIV RNA levels. Phillips and colleagues analyzed data from therapy-naive patients starting antiretroviral therapy who participated in 3 large cohort studies and found that lower CD4 cell counts and higher viral load levels at baseline were not associated with poorer virological response to antiretroviral therapy. In a population-based study of therapy-naive patients starting antiretroviral therapy, Hogg and colleagues found that risk of progression to AIDS and mortality was significantly higher among patients with baseline CD4 cell counts less than 200 cells/µL, but baseline plasma HIV RNA level was not an independent prognostic indicator. In an editorial, Pomerantz discusses the implications of these findings for initiation of antiretroviral therapy.

Editorial: Initiating Antiretroviral Therapy During HIV Infection
Confusion and Clarity
Roger J. Pomerantz, MD
Excerpt:
"Following the development of HAART, many physicians were quite aggressive in treating patients at virtually any stage of this human retroviral disease, almost regardless of the CD4 T-lymphocyte count and plasma HIV RNA level. Because of the increasingly reported serious adverse effects of the diverse drug constituents of HAART, studies were conducted to attempt to determine the time at which initiation of ART was most efficacious, based on clinical end points and surrogate markers. [...] Based on these studies, several somewhat divergent clinical conclusions could be drawn. Nevertheless, it seems that a reasonable conclusion would be to focus primarily on the CD4 T-lymphocyte count for determining initiation time for ART in many infected patients. A CD4 T-lymphocyte count of 200 106/L in peripheral blood appears to be the critical level in the study by Hogg et al9 and in previous analyses,5 and it would seem prudent to ensure that ART is initiated before CD4 T-lymphocyte counts decrease below this level. Acknowledging that this parameter does not apply to all patient subgroups, most patients could be monitored closely, rather than immediately beginning therapy with drugs that have potential significant adverse effects over several years of therapy (eg, lipodystrophy, mitochondrial toxicity, lipid abnormalities, osteopenia, and lactic acidosis)."

Abstracts:

Rates of Disease Progression by Baseline CD4 Cell Count and Viral Load After Initiating Triple-Drug Therapy
Hogg, et al. JAMA. 2001;286:2568-2577

HIV Viral Load Response to Antiretroviral Therapy According to the Baseline CD4 Cell Count and Viral Load
Phillips, et al. JAMA. 2001;286:2560-2567