“Our results suggest patients at most risk are those taking just enough medication to allow resistant virus mutations the opportunity to replicate, instead of reducing the viral load to levels so low it can’t replicate at all,” says Dr. Richard Harrigan, director of the Centre’s Research Labs. “In short, the results prove HIV drug regimens are nothing like a game of horseshoes – close is not good enough.”

In B.C., all anti-HIV medications are distributed at no cost to eligible HIV-infected individuals through the Centre’s Drug Treatment Program. People with HIV are prescribed a complicated combination of drugs – commonly referred to as triple-drug therapy -- to suppress the disease. Drug resistance occurs when HIV replicates and mutates to form a strain resistant to the drugs designed to fight it. Patients are then prescribed alternative combinations of drugs. Success, however, is never guaranteed. Drug-resistance is often cited as a significant barrier to long-term treatment efficacy and a major cause of overall treatment failure.

The Centre’s investigation into the causes of HIV drug resistance is the first based on a cohort, or ongoing study, of patients starting triple-drug therapy. Previous studies were based on short-term clinical trials or included patients who were drug-therapy experienced.

“The problem with clinical trials is they are short term, people drop out and some only study one or two drugs. In this study, we followed a large group of people beginning triple drug therapy for 30 months on a wide variety of drug regimens,” says Harrigan.

Harrigan presented the research findings at a New York media conference organized by the American Medical Association. The press conference spotlighted “HIV/AIDS: The Drug Resistance Epidemic.” Past AMA media events have attracted major media outlets such as CNN, NBC the Wall Street Journal, Chicago Tribune, New York Times, and various freelance science and health journalists.

The Centre study, to be published by the international Journal of Infectious Diseases Feb. 1, followed more than 1,000 people who were beginning drug therapy over 30 months (1996-1999). Adherence to the medication regimen (measured by the number of filled prescriptions) had the greatest impact on drug resistance. Patients were divided into groups according to what percentage of their prescriptions they filled: 0 to 20%, 20 to 40%, 40 to 60 %, 60 to 80%, 80 to 90%, 90 to 95 percent and 95 percent or more. Patients who missed less than five per cent of their medications were least likely to develop resistance. However, those who took their medication 80 to 90% of the time were most likely to develop resistance. As well, those with a high HIV viral load (over 100,000 copies per millilitre) starting drug therapy were also more likely to develop resistance. At the end of the study period, 30% of the study group developed drug resistance. The average time to develop resistance for those affected was 8.3 months.

The study findings highlight the need to be more cautious of patients with high viral loads as well as find means to improve patient adherence, says Harrigan.

“We’re going to have to be a lot more vigilant both in terms of the drugs we give them and how they’re taking them,” says Harrigan. “We also have to continue to improve adherence through advancements in drugs. The good news is that we increasingly have more, and better, drugs – as well as a better understanding of how to give them. We are working to make taking them as simple as possible.”

The study outcome was never for certain, stresses Harrigan. In fact, the findings differ from those of a recent international study (“High levels of adherence do not prevent accumulation of HIV drug resistance mutations,” AIDS 2003, 17:1925-32) that concluded high levels of adherence does not prevent accumulation of drug-resistance mutations. However, the particular study included individuals with considerable prior drug therapy experience

While those who largely do not adhere to their drug regimen do not develop drug resistance, they do greatly increase the risk of dying. Last August, the Centre released a paper in the international Journal of Infectious Diseases that found 56% per cent of HIV-infected individuals in B.C. who used available drug treatment intermittently or discontinued it prematurely died of HIV-related causes.

Access to anti-HIV drugs is also key. A Centre study released in October 2003 revealed one third of people who died from HIV-related causes did not receive any life-saving treatment.

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For information or interview requests, please contact Glen Edwards, media relations, 604.623.3007. Dr. Harrigan is available via cell phone the morning of Wednesday, Jan. 12, as well as 11 a.m. onward on Thursday, Jan. 13. If you are seeking comment from the AMA, please contact Jeanne Galatzer-Levy, Public Information Officer, 1- 312-464-5980 (Chicago) or their general media dept. at 1-312-464-2410.

Backgrounder

About the B.C. Centre for Excellence in HIV/AIDS
Founded in 1992 by St. Paul’s Hospital and the provincial Ministry of Health, the B.C. Centre for Excellence in HIV/AIDS is a key provincial resource seeking to improve the health of people with HIV through the development, ongoing monitoring and dissemination of comprehensive investigative and treatment programs for HIV and related diseases. St. Paul’s Hospital is one of six health care facilities operated by Providence Health Care, Canada’s largest faith-based health care organization.

About the American Medical Association
The American Medical Association is the country’s largest physician group. As the national professional organization for all physicians, the AMA serves as the steward of medicine and leader of the medical profession. The AMA’s House of Delegates comprised of physician delegates representing every state; nearly 100 national medical specialty societies; federal service agencies, including the Surgeon General of the United States; and six sections representing hospital and clinic staffs, resident physicians, medical students, young physicians, medical schools and international medical graduates. For more information on AMA, please visit www.ama-assn.org

About triple drug therapy/HAART
While HIV never disappears, the goal of triple drug therapy, or highly active antiretroviral therapy (HAART), is to reduce the amount of HIV virus in the body as low – and for as long – as possible. Different classes of drugs work by stopping parts of the virus so the virus can't make more of itself. Research has shown that using combinations of three drugs from at least two different classes to prevent the virus from replicating is a better treatment strategy than using only one or two drugs.

About drug resistance
HIV does not always make perfect copies of itself. With billions of viruses being replicated daily, lots of small, random differences can occur. These differences are called mutations. Mutations that change parts of the virus where the drugs are meant to stop can keep the drugs from working. When a drug no longer works against HIV, this is called drug resistance.

About viral load
Viral load is expressed as the number of copies of HIV RNA per millilitre of blood plasma. The lower the viral load, the longer the time to AIDS diagnosis and the longer the survival time. Viral load is often used an indicator of virus concentration and reproduction rate and, as a result, a measure of the success of drug therapy.