A 'cocktail' treatment of several drugs offers hope

MARK NICHOLS,M. N. July 15 1996


A 'cocktail' treatment of several drugs offers hope

MARK NICHOLS,M. N. July 15 1996


A 'cocktail' treatment of several drugs offers hope



According to the careful record he keeps, Jim Wakeford has lost 239 “friends, lovers and acquaintances” to AIDS since 1984. For the past three years, Wakeford, 51, has been battling the symptoms of his own case of AIDS, which include an alarming downward spiral in the number of vital T4 cells in his blood. In a healthy person, there are usually 1,000 or more of the cells—a critical component of the body’s immune system—per cubic centimetre of blood. Two years ago, Wakeford’s count was about 90. But since he began taking two new drugs five months ago, his T4 count has risen to 250. The drugs that seem to be making the difference are known as protease (pronounced PRO-tee-aze) inhibitors—a family of powerful new combatants in the war against AIDS. Taken with other drugs in a kind of pharmaceutical “cocktail,” they have produced spectacular improvement in some patients. Mainly for that reason, the eleventh International Conference on AIDS taking place in Vancouver this week is billed as an occasion for more optimism than at almost any time since the AIDS epidemic began 15 years ago.

Participants were looking forward to more encouraging news as thousands of scientists from around the world gathered to report their latest findings. Said Dr. Michael Rekart, an infectious disease expert who is chief of the B.C. health ministry’s AIDS control program and one of the conference’s four co-chairmen: ‘There is a reasonable hope now that we will be able to cure this disease someday.” The six-day conference, held under the auspices of the Stockholm-based International AIDS Society, brings together more than 15,000 researchers, doctors and support workers, and about 1,500 journalists. And apart from the exchange of information, it provides the potential for political fireworks from a community well-known for its ability to speak up for itself. Canadian AIDS activists, for example, were furious at Prime Minister Jean Chrétien for declining an invitation to open the conference—he sent Health Minister David Dingwall instead. They are even angrier over Ottawa’s plan to wind up its six-year-old, multimillion-dollar National AIDS Strategy in March, 1998. Dr. Martin Schechter, director of the Vancouver-based Canadian HIV Trials Network and another conference cochairman, called the decision “bad social policy and worse economic policy. It’s incomprehensible.”

The Vancouver meeting is taking place in the shadow of a grim anniversary: 15 years have passed since U.S. health authorities, in June, 1981, first officially reported a rare type of pneumonia

among gay men. Since then, the disease that in 1982 came to be known as acquired immune deficiency syndrome has exploded into an epidemic that has killed more than 4.5 million people around the world and is currently making its deadliest inroads in the developing nations of Africa and Asia. In Canada, despite evidence that the epidemic has levelled off from the high rates of infection during the mid1980s, AIDS still kills at an alarming rate. It has claimed the lives of about 10,000 Canadians, the majority of them homosexual and bisexual men, and is the leading cause of death among men between the ages of 25 and 44 in Montreal, Toronto and Vancouver.

Now, even as the overall infection level drops, the disease is taking a rising toll among injection drug users, young gay men, women and native Canadians (page 43). Jeff Dodds, who runs the volunteer organization AIDS Saskatoon, says that in his part of the country, “the epi] demie is still growing. We’re seeing a steady increase every year in the number of new cases.”

Paradoxically, the disease that has killed thousands of homosexual and bisexual men has also helped to strengthen the cohesiveness and visibility of the gay movement, which mobilized to protect its own interests.

That, in turn, has contributed to the achievement of greater legal recognition, including health-care and other employment benefits for same-sex couples and increased protection against discrimination. At the same time, the gay community has suffered enormously. “The gains we’ve made in terms of social tolerance for gays,” says Russell Armstrong, executive director of the Ottawa-based Canadian AIDS Society, “have been at a cost that is beyond words.”

Homophobia contributes to a powerful stigma that still clings to a disease that, in North America, is most frequently transmitted through homosexual contact. The means of transmission is through the exchange of semen or blood—meaning that unprotected sex or needle sharing by drug users are high-risk activities. Until recently, researchers believed that oral sex was probably safe. Then in May, scientists in Boston warned the virus could probably be communicated orally after all:

when technicians put doses of a virus resembling HIV—the one associated with AIDS—in monkeys’ mouths, the animals became ill.

Beyond the established causes, misunderstanding and paranoia abound. Although there is absolutely no evidence of AIDS being transmitted by touch or through the air—from talking, coughing or sneezing, for instance—many health workers still take extraordinary, and according to AIDS sufferers, demeaning, precautions. “In small Nova Scotia hospitals,” said Jean MacQueen, executive director of the Sydney, N.S.-based AIDS Coalition of Cape Breton, “if you’re HIV-positive, you still get nurses coming into the room wearing gloves and masks.” Similarly, since the AIDS epidemic began, dentists and their assistants throughout North America have donned gloves and masks even for routine examinations.

One confirmed method of transmission has been blood and blood products used in transfusions. Until the Canadian Red Cross Society began screening for HIV in donated blood in 1985 and tightened its procedures, an estimated 1,200 Canadian hemophiliacs and other recipients of blood and blood products contracted

AIDS. An inquiry under Justice Horace Krever of the Ontario Court of Appeal wound up hearings into the tainted-blood tragedy in December. But Krever’s final report, due in September, will come too late for the many infected by tainted blood and blood products who have already died of AIDS.

Now, improved drugs—and promising combinations of drugs— are beginning to restore a measure of health, and hope, to thousands of AIDS patients. Ten years in development, the new class of drugs called protease inhibitors are producing impressive results. U.S. doctors who use them along with other drugs to treat some HIV-positive patients at an early stage report that within months they can detect no trace of HIV in the patients’ blood. In other cases, notes Rekart, some patients with full-blown AIDS who were treated by combination drug therapy built around protease inhibitors “have literally been brought back from the point of death.” Although three of the new protease inhibitors have been approved in the United States, only one—Hoffmann-La Roche’s saquinavir (brand name Invirase)—has so far been approved for


iwWk general use in Canada. Ottawa’s health protection branch is currently reviewing Abbott Laboratories’ ritonavir (Norvir) and Merck & Co.’s indinavir (Crixivan), with approval expected by the fall.

Peter Barbiéri, a 28-year-old Montrealer who tested HIVpositive in 1988, has been taking saquinavir since March. Before he started on the drug, Barbiéri was plagued by chronic fatigue, weight loss and bouts of diarrhea— and says that his T4 cell count had fallen to zero. Since then, Barbiéri, who said that he probably acquired AIDS through gay sex, has gained 30 lb., the diarrhea has stopped and his T4 count has climbed to 36. “There have been major improvements in every area of my health,” said Barbiéri, who quit his job with a Montreal furniture retailer in May. “I feel much better.” Yet like many other AIDS

sufferers and their doctors, Barbiéri wonders whether the new combination drug thera-

py will keep on working. In

But will the drug therapy keep oi

the past, some AIDS drugs have failed to live up to their early promise. AZT, introduced during the mid-1980s, at first proved effective in clearing HIV out of patients’ bloodstreams. But for many patients the effects lasted only for a year or so—after which the virus mutated into drug-resistant forms and resumed its lethal attack on the victims’ immune systems. Some doctors and AIDS workers fear that may happen again. “We’re concerned,” said Philip Hannan, spokesman for the volunteer organization AIDS Vancouver, “that reports of the new drugs’ effectiveness may be overblown.”

James Smyth, 40, a Winnipeg hemophiliac who was diagnosed HIV-positive in May, 1984, sees no need yet for a protease inhibitor, despite their apparent effectiveness in the earliest stages of infection. In fact, he is not taking any AIDS drugs because he has yet to develop serious symptoms of the disease. “I’ll let my body go on fighting the disease as long as it can,” says Smyth. Over the years, he has seen more than a dozen of his hemophiliac friends die of AIDS contracted after using tainted blood-clotting

products—and he fears the side-effects, including nausea and fatigue, that some AIDS drugs can cause. Smyth stopped working as a salesman for a firm that sells household alarm systems in 1989, because of fatigue caused by his HIV infection. And he realizes that he may eventually develop debilitating AIDS symptoms. If that happens, he says, “I will definitely consider going onto combination drug therapy. For now, I just put things in God’s hands.” Many medical researchers are convinced that this time they may have found a way to defeat HIV—with a combination of drugs that box in the virus and, by drastically limiting its ability to reproduce itself, reduce its chances of producing new, drug-resistant mutations. Protease inhibitors play a central role in the strategy by blocking an enzyme that HIV uses to reproduce itself inside a victim’s blood cells. Potent by themselves, the protease inhibitors work even better in combination with such drugs as AZT and 3TC—a widely used medication developed by scientists at Montre al’s BioChem Pharma Inc.—which attack enzymes used at later stages in HIVs reproductive cycle. ‘We’re on the threshold,” said


An outbreak of uncommon pneumonias, cancers and other ailments among homosexual men in Los Angeles and New York City is dubbed “gayrelated immune deficiency,” or “gay plague."

Transmission linked to sex.

American and French scientists discover the virus associated with AIDS, later dubbed “human immunodeficiency virus,” or HIV.

Global toll of reported deaths to date hits 100,000.

1981 1982 1983 1984

Outbreak renamed “acI Transmisquired immune deficient sion linked cy syndrome," or AIDS. 11 to blood.


1985 1986 1987 1988

Test developed to show presence of HIV.

Screen star Rock Hudson dies of AIDS.

AZT approved as AIDS treatment.


Michael O’Shaunessy, a leading Vancouver researcher and conference co-chairman, “of actually being able to talk about AIDS as a manageable disease.”

The benefits, however, will be far from universal. Expensive new drugs are unlikely to make much difference in the Third World, where medicines of any kind are scarce—and where AIDS is spreading with savage energy. According to United Nations estimates, 21 million adults and about three million children around the world are infected with HIV, with more than 90 per cent of the cases in developing nations. Worldwide, about 1.3 million people have full-blown AIDS—in which the immune system has collapsed, exposing the victim to pneumonia and other so-called opportunistic infections. In 1995, nearly a million died of AIDS-related diseases.



he two scientists met

in a bar at Montreal’s Windsor Station. It was January, 1988, and Mark Wainberg, a McGill University professor of medicine, had tested a series of experimental drugs developed by a former colleague who had gone to work for a small Montreal firm called BioChem Pharma Inc. According to Wainberg’s tests, one of chemist Bernard Belleau’s drugs appeared effective in preventing the AIDS virus from replicating inside the human body. Belleau, however, was upset because other labs that

tested the drug found it ineffective, and he wanted to know what that meant. “I told him," Wainberg says, “that it meant our lab was right and the others were wrong.” Wainberg’s findings were indeed correct. Belleau died of a heart attack in 1989, but his discovery—now known to the world as 3TC—is used by thousands of AIDS patients to blunt HIV’s attack on the immune system. “I think,” says Wainberg, director of McGill’s AIDS Centre, which co-ordinates multidisciplinary research, “that some day 3TC may be recognized as Canada’s most important medical contribution after the discovery of insulin in 1921.”

Belleau’s drug is based on a synthetic molecule that disrupts HIV’s reproductive process, while causing relatively few side-effects. Once it was clear that the drug was

effective, BioChem Pharma entered into a licensing agreement with the British drug giant Glaxo Wellcome Inc. to develop and market 3TC. Approved for use in the United States and Canada late last year, 3TC had retail sales in the two countries worth more than $56 million in the first three months of this year.

Now, a Winnipeg team is working on a new approach aimed especially at the later stages of AIDS. In 1991, Bert Friesen, a University of Manitoba-trained chemist, began thinking about the way HIV uses a genetic tool called messenger RNA to seize control of human blood cells. To thwart that process, Friesen and biochemist Jim Wright designed a strand of genetic material that prevents the virus from using other cells to reproduce itself. This fall, Friesen plans to begin human tests of the new drug, known as GPI2A—-a potential new Canadian winner in the war on AIDS.

M. N.

According to the United Nations’ Joint HIV/AIDS Pro| gram, more than 13 million adults are infected in south| ern Africa alone, where the disease is transmitted mainly I by heterosexual contact. Though there are signs that the g rate of infection may be levelling off, close to one-fifth of s adult males in some African nations now carry the virus. In Asia, the disease is still spreading rapidly. Thailand, with an estimated two per cent of all adults infected, has the highest rate of infection in the world. India, with an estimated 1.7 million people carrying the virus, has the most infections.

In North America, campaigns to promote safe sex in high-risk segments of the population seem to be paying off. The rate of infection in the United States appears to have declined dramatically—though AIDS remains the largest killer of men aged 25 to 42. And in Canada, federal officials say that the infection rate now is running at less than half the level it reached during the mid-1980s,

World Health Organization says 10 million people are HIV-positive.

Basketball superstar Magic Johnson reveals he is HIVpositive.

Supreme Court upholds conviction of Ottawa resident James Charles Thornton of committing a common nuisance by donating blood despite knowing he was HIV-positive.

Dartmouth, N.S., hemophiliac Randy Conners dies of AIDS complications after spearheading successful campaign with wife Janet—who contracted AIDS from him—for financial compensation for victims of contaminated blood.

Some 21 million worldwide are HIV-infected and 1.3 million (more than 18,000 Canadians) have full-blown AIDS. More than 4.5 million have died.

Charles Ssenyonga dies of AIDS complications before a judge in London, Ont., can rule on whether he committed a crime by infecting three women with HIV.

The WHO predicts 40 million HIV infections by the year 2000.

Protease inhibitors show promising results.


approved as treatment.


Fewer infections are being reported, but the risk is rising among women and intravenous drug users

when more than 8,000 Canadians were being infected annually. At the same time, the average age of infection in Canada fell to 23 from 32 in the early years of the epidemic, and the infection rate is rising rapidly among intravenous drug users—and among women, many of whom are acquiring HIV from sexual partners who inject drugs.

That drug connection, say experts, represents an increased threat to the general population—because people who are high on drugs, in poor health or living on the streets are unlikely to practise safe sex. “There is a lot of fear,” says David Thompson, executive director of AIDS Community Care Montreal, “that injection drug users are the bridge to the heterosexual community.”

Meanwhile, AIDS victims face challenges on the financial front as they struggle to pay for the drugs that may save their lives. Patients who use a protease inhibitor in combination with two, and sometimes three, other anti-viral drugs can face outlays of more than $15,000 a year. Many private drug plans do not cover the costly new drugs—and the amount of financial help offered by the provinces varies widely. Saskatchewan covers all major drug costs for AIDS patients. Both Alberta and New Brunswick cover the cost of some AIDS medications—but neither helps pay for protease inhibitors. In Quebec and Ontario, AIDS drugs are covered under various provincial health plans. But in Ontario, a delay in processing applications has left some AIDS patients frustrated and angry. Says Wakeford: “This is a mean, mean province right now.”

Organizations devoted to helping people with HIV or AIDS and funding the medical research into the disease have other financial concerns. Health Minister David Dingwall’s predecessor, Diane Marleau, decided during her period in office that the federal government would wind up its National AIDS Strategy when its current five-year phase ends in March,

1998. Under that $203-million program, Ottawa currently directs $17.8 million a year towards researching and tracking the disease, $9.8 million to AIDS organizations that provide educational and support services, and the rest to treatment and other services. If the strategy is phased out, AIDS groups and medical researchers would have to apply on an individual basis for federal funding—and would likely receive less overall from a government intent on reducing its budget deficit.

Faced with furious protests from researchers and AIDS activists, Ottawa is reviewing the cancellation. Dingwall, saddled with Marleau’s decision, is currently meeting with AIDS organizations and researchers to discuss future funding arrangements. He told Maclean’s last week that when that process is completed—probably before the end of the year—“I will be in a position to see what we can do to extend the strategy, or determine some new way of extending assistance.” But Dingwall also noted that the cancellation was motivated in part by Ottawa’s desire to put AIDS on the same footing as other major diseases, such as cancer and heart disease, in the competition for funding.

Activists maintain that stopping the program would seriously undermine AIDS research in Canada, which already ranks last in per capita spending among the world’s seven richest industrialized nations, and cripple support organizations in poorer provinces. Critics noted that when Chrétien attended the 1994 Paris AIDS summit with other world leaders, he pledged that fighting the disease would be a priority for his government. “Now,” said Vancouver’s Schechter, “it’s really time for this government to deliver on that promise.” With successful treatment, if not an outright cure, already in their sights, AIDS researchers see this as no time to abandon the fight. □