The Bay Area Reporter - March 6, 1998
Matthew Sharp, ACT UP/Golden Gate Writers Pool

New data from abacavir is becoming available as researchers, clinicians, and patients are gaining experience with the drug. Some of the information is positive and some negative. Abacavir is appearing to be just another nucleoside analog sharing common resistance patterns and toxicities with its cousins, AZT, ddI, d4T, and 3TC. Activists, disturbed and frustrated over the latest data, want to inform people with AIDS about the problems with abacavir.

The 5th Conference on Retroviruses and Opportunistic Infections in Chicago highlighted several 1592 studies, which showed significant viral load decreases. However, other information coming from the expanded access program for people who have taken the arsenal of AIDS drugs is bringing disappointing efficacy information. And most seriously, without warning, abacavir has caused serious life-threatening hypersensitivity reactions, which has led to three deaths.

The good news:

After 16 weeks of follow-up, most patients in a John Mellors (University of Pittsburg) study had a 1.8 to 2.4 log decline in viral load. All of the participants had not used antiretrovirals and had a minimum of 500 CD4 cells with a baseline of less than 5,000 viral RNA. After 16 weeks on one of five protease inhibitors in combination with abacavir, up to 85 percent of people in the study had more than 400 copies of HIV and 70 percent of those patients had more than 50 viral load. According to this study, abacavir with a protease inhibitor seems to be quite potent combination in patients not previously treated with HIV drugs.

Now the bad news:

Though there was a good antiviral response in the Mellors study, four of the 78 patients (approximately five percent) developed an acute hypersensitivity reaction to the drug. This means that several people developed a mild fever, malaise, and other symptoms - with or without rash caused by an initial drug reaction to abacavir. Then, four people who went back on the drug developed a life-threatening reaction that sent them to intensive care to be resuscitated. One person died in this study due to the hypersensitivity.

This hypersensitivity is uncommon in AIDS drugs. Drugs to prevent PCP such as septra (bactrim) and non-nucleoside drugs such as nevirapine and delavirdine have caused reactions, but nothing as severe as to cause ICU visits and death. We may be seeing more of these toxic reactions as more drugs are available and being combined. The severity of this situation has forced people with AIDS to rethink early access to new drugs.

Further bad news is that the drug may have little or no effect in people who have been on other nucleoside drugs such as Glaxo's AZT and 3TC. The patterns of mutations are similar to its cousins and are probably the reason it has little effect in experienced patients. Ben Cheng from Project Inform puts it this way, "If you only have resistance to AZT you may be okay, and if you have resistance only to 3TC you may be okay, but if you are resistant to two or more nucleosides, abacavir may not be as effective." This does not bode well for many patients who have used up the famous AZT/3TC cocktail and have been treated with all the protease inhibitors.

The 1592 experience poses a predicament to people with AIDS. When there are much more options available today, do we continue to risk drug reactions by having early access to ill-studied therapies? Do some of us have the luxury of waiting? Should tactics be modified to wait for new options until more people have been studied or do we continue to fight for mediocre drugs that the pharmaceutical industry can profit on?

Glaxo Wellcome is clearly trying to corner the HIV market with AZT, 3TC, and combavir (a combination of AZT and 3TC). Add to the mixture the Glaxo darling drug, abacavir. They even have their own protease inhibitor, amprenavir (141W94) that is being studied in combination with AZT, 3TC, and abacavir. They recently bought out Hoescht, which has several non-nucleoside drugs in development. With this plan, anyone can see that the company plans to cover all the bases when it comes to HIV drug cocktails. So, one must question whether Glaxo is just trying to profit from their own drugs, or are helping to find the best treatments for AIDS?

On the horizon

It is clear that many questions need to be answered before we throw in the towel on demanding early access. The desperation that caused the outcry over access to abacavir was real and activists responded appropriately. At the time people had used up the nucleoside generation of drugs and there was nothing new on the horizon except abacavir. Today, on the contrary, there are 12 HIV drugs approved, three in expanded access, and several more in the research pipeline; one might wonder how we can still demand early access in light of this bleak information about abacavir but, given the complexity and reality of this disease, there will still be people who need drug options. ACT UP/Golden Gate still supports access to any drug a patient needs to stay ahead of progression and death. Ultimately, it should be left up to the patient and their physician.

Hank Wilson, a longtime AIDS activist and member of ACT UP/Golden Gate, was losing the battle with HIV a year ago. He had tried all the anti-HIV drugs and had 30 CD4 cells with a viral load of 590,000. "I couldn't articulate what I wanted to say and I was hospitalized with cryptococcal meningitis," Wilson now recalls. He became the first patient on abacavir in San Francisco in a study for dementia at General Hospital. "After 12 weeks on placebo I was switched to 1592 and added delavirdine and viracept," he says. "Then, in just one week I had the capacity to think clearly again. My CD4 count went to 350 and my viral load dropped to 7,000. Now, after one year I have no detectable virus and I feel like the old Hank."

Wilson's experience with abacavir is exactly why activists still believe early access can be life saving. Abacavir has been available for people below 50 CD4 counts for months now in a limited expanded access program. A wider program that would match programs offered by the new Gilead drug, Preveon (adefovir) and DuPont Merck's Sustiva (DMP-266) has been delayed by bureaucratic regulations and by Glaxo incompetence, but should be announced soon.

Wilson muses, "When I visit friends in the dementia ward I wish they could experience the response I had with 1592. People with dementia shouldn't be written off. New drugs like 1592 can give people the capacity to turn around." Clearly, there are many people who can benefit from early access to AIDS drugs. How best to balance the need with safety concerns in early access will continue to be a struggle in the coming years. t
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