Drug Therapy

“A Ray of Hope in the Fight Against Aids,” read the headline in the September 29, 1986, issue of Time magazine. This “ray of hope” was generated by the results of a clinical trial using azidothymidine (AZT), an antiretroviral drug, to treat HIV. Remarkably, HIV patients who took AZT were living longer. Since that time, antiretroviral drugs (ARVs) have prolonged the lives of hundreds of thousands of people. (See the box “What Are ARVs?” on page 7.) How successful have they been in treating HIV infection?

Despite the initial enthusiasm surrounding the release of AZT, Time magazine reported that AIDS researchers “were confident that AZT [was] not the ultimate weapon against AIDS.” They were correct. Some patients were unable to tolerate AZT, so other ARVs were developed. Later, the U.S. Food and Drug Administration approved a combination of ARVs for advanced HIV patients. Combination therapy, which came to involve the taking of three or more antiretroviral drugs, was enthusiastically welcomed by AIDS workers. In fact, at an international conference on AIDS in 1996, one doctor even announced that the drugs may be able to eliminate HIV entirely from the body!

Sadly, within a year it was evident that even strict adherence to the three-drug regimen could not eradicate HIV. Nonetheless, a report by UNAIDS says that “combination ARV therapy has enabled HIV-positive people to live longer, healthier, more productive lives.” In the United States and Europe, for example, ARV use has reduced AIDS deaths by over 70 percent. In addition, several studies have shown that selected ARV treatment can dramatically reduce HIV transmission from an infected pregnant woman to her child.

Yet, millions of HIV patients are denied access to ARVs. Why?

“A Disease of Poverty”

ARV therapy is widely administered in high-income countries. However, the World Health Organization (WHO) estimates that in some developing lands, only 5 percent of those who need ARV therapy have access to the drugs. United Nations envoys have gone so far as to describe this imbalance as “a serious injustice” and “the grotesque obscenity of the modern world.”

Unequal access to therapy can also exist among citizens of the same country. The Globe and Mail reports that 1 in 3 Canadians who die of AIDS has never been treated with ARVs. Even though the drugs are available free of charge in Canada, certain groups have been overlooked. “Those missing out on proper treatment,” says the Globe, “are those in most desperate need: aboriginals, women and the poor.” The Guardian quoted one African mother who is HIV-positive as saying: “I don’t understand it. Why do these white men who have sex with men get to live and I have to die?” The answer to her question lies in the economics of drug production and distribution.

The average price of a three-drug ARV regimen in the United States and Europe is between $10,000 and $15,000 a year. Even though generic copies of these drug combinations are now being offered in some developing countries at a yearly rate of $300 or less, this is still far beyond the reach of many who have HIV and live where ARVs are needed the most. Dr. Stine sums up the situation this way: “AIDS is a disease of poverty.”

The Business of Making Drugs

Developing generic versions of patented drugs and selling them at reduced prices has not been easy. Strict patent laws in many countries prohibit the unauthorized reproduction of brand-name drugs. “This is an economic war,” says the head of one large pharmaceutical company. Producing generic drugs and selling them to developing countries for a profit, he says, “isn’t fair to people who have discovered those drugs.” Brand-name drug companies also argue that diminishing profits could result in reduced funding for medical research-and-development programs. Others worry that low-cost ARVs destined for developing countries could actually end up on the black market in developed lands.

Proponents of low-cost ARV drugs counter that new drugs can be produced at between 5 and 10 percent of the costs suggested by the pharmaceutical industry. They also say that research and development by private pharmaceutical companies have tended to neglect diseases afflicting poorer countries. Thus, Daniel Berman, coordinator of the Access to Essential Medicines project, states: “For new drugs, there needs to be an internationally-supported enforceable system that reduces prices to affordable levels in developing countries.”

In response to this global need for ARV therapy, WHO has developed what is described as the three-by-five plan to provide ARVs to three million people living with HIV/AIDS by the end of 2005. “The three-by-five target must not become another unmet UN target,” warned Nathan Ford of Médecins Sans Frontières. “It is only half the number of people with HIV/AIDS estimated to need treatment today and this number will be much greater [by 2005].”

Other Obstacles

Even if enough ARVs were supplied to developing lands, other obstacles would have to be overcome. Some drugs need to be taken with food and clean water, but hundreds of thousands of people in some lands can eat only every other day. ARVs (often 20 or more pills daily) need to be taken at a certain time each day, but many patients do not own a timepiece. Drug combinations need to be adjusted according to a patient’s condition. But there is a critical shortage of physicians in many lands. Clearly, providing ARV therapy to developing countries will be a difficult hurdle to surmount.

Even patients in developed lands face challenges in using combination therapy. Research reveals that failure to take all prescribed drugs at scheduled times is alarmingly common. This may lead to drug resistance. Such drug-resistant strains of HIV can be transmitted to others.

Dr. Stine points to another challenge faced by HIV patients. “The paradox of HIV treatment,” he says, “is that sometimes the cure feels worse than the disease, especially when treatment begins before symptoms arise.” HIV patients on ARVs commonly suffer from side effects including diabetes, fat redistribution, high cholesterol, and decreased bone density. Some side effects are life-threatening.

[Box/Pictures on page 7]

What Are ARVs?a

In a healthy person, helper T cells stimulate or activate the immune system to attack infections. HIV particularly targets these helper T cells. It uses the cells to replicate itself, weakening and destroying helper T cells until the immune system is severely compromised. Antiretroviral drugs (ARVs) disrupt this replication process.

Currently, four main types of ARVs are administered. Nucleoside analogues and non-nucleoside analogues prevent HIV from copying itself onto a person’s DNA. Protease inhibitors block a specific protease enzyme in infected cells from reconstructing the virus and producing more HIV. Fusion inhibitors aim to prevent HIV from entering cells. By suppressing HIV replication, ARVs can slow the progression from HIV infection to AIDS, dubbed the most severe clinical form of HIV disease.

[Footnote]

[Picture]

KENYA​—A doctor instructs an AIDS patient about ARV treatment

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© Sven Torfinn/Panos Pictures

[Picture]

KENYA​—An AIDS patient receives her ARV medicine at the hospital

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© Sven Torfinn/Panos Pictures