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AIDS drug offers hope, but too late for one man

January 02, 2007|James Ricci | Times Staff Writer

2006 was destined to be the year Warren Ratcliffe lost his desperate race to survive AIDS, and the year Mark McClelland appeared, finally, poised to win his.

The two Bay Area men were among an estimated 40,000 Americans whose illness could not be controlled by modern HIV drugs because they'd developed a bedeviling resistance to them. Known as "salvage therapy" patients, they had only one hope: that a complicated and ever-changing witch's brew of existing medications, aimed at stalling the famously mutational virus, would keep them alive long enough for entirely new drugs to arrive via the pharmaceutical research pipeline.

In 2006 just such a drug -- one that some researchers are calling "truly phenomenal" -- did come along, in time, doctors hope, to save the 45-year-old McClelland but too late for Ratcliffe, who was overtaken by AIDS-related cancer and died April 27 at age 58.

The new drug, called an integrase inhibitor, was a highlight of the summer's annual international AIDS conference in Toronto. Newly published clinical studies showed that it, in combination with two existing drugs, reduced the virus to undetectable levels in nearly 100% of HIV patients taking, for the first time, a regimen targeting their condition. It had a similar effect on the virus in up to 72% of salvage therapy patients.

"They tested it on some people who were in deep, deep salvage therapy, and even those people did remarkably well," said Dr. Steven Deeks, a UC San Francisco salvage therapy authority who treated Ratcliffe and still treats McClelland. "It seems to be a truly phenomenal drug that everyone is sort of a little bit in awe of right now and is changing the whole way we think about the management of these patients."

The drug essentially prevents the virus from integrating its DNA with that of a host's cells, thus short-circuiting its ability to replicate itself.

McClelland had several friends in salvage therapy who were part of the integrase inhibitor studies. "They all did extremely well," he said.

The knowledge of how they fared was immensely encouraging to him. And his own recent negative experience propelled him in the same direction.

In October, he came down with a fungal infection that took advantage of his lowered immune defenses.

"It was semi-serious but treatable," he said. "Getting sick hit me emotionally, however. I was just coasting along, and it was an opportunistic infection, and I hadn't had one of those in 11 years. And that was tough and gave me some renewed determination."

What was more, McClelland's count of infection-fighting T-cells, a principal indicator of immune system compromise, hit zero. "It wasn't too different from four, which I've hit before, but there's something about hitting zero that was a little upsetting."

Ratcliffe could not be included in the clinical studies of the integrase inhibitor. Kaposi's sarcoma, the early AIDS epidemic's portentous and deadly calling card, was overwhelming him.

"Warren really couldn't qualify for the drug, because his Kaposi's was progressing and because he had pretty significant side effects from the chemotherapy," Deeks said. "Mark is doing well, however, and I'm trying to get him on the integrase inhibitor right now. We're trying to get as many people in our research cohort as possible on this."

The new drug is on track for FDA approval by mid-2007, but its manufacturer, Merck & Co., is making it available sooner to patients in desperate straits.

Ratcliffe and McClelland were featured last January in a Times article about their unlucky subgroup and the obscure corner of AIDS treatment it occupies.

Like most others in their category, they had the misfortune of being diagnosed with HIV when single-drug treatment, called monotherapy, was the only help available. With monotherapy, the virus had to mutate past only one drug, which made a patient resistant to that medication and all others of its type.

Multi-drug therapy, which became available a decade ago, usually presents HIV with too many obstacles for it to mutate past. This therapy became the gold standard of treatment, suppressing the virus and allowing patients to live normal lives.

The multi-drug "cocktail" failed to work for monotherapy veterans like Ratcliffe and McClelland, because in them, the virus had already become resistant to one of the cocktail's components and was more likely to resist other drugs in the mix, as well.

Ratcliffe's deterioration and death just as a potentially saving drug was becoming available has inflicted an added measure of pain on Alex Kazan, his domestic partner of 10 years and friend of 25.

"Watching him go was pretty difficult, because he was such a wonderful, caring person," Kazan said. "You wonder why he couldn't have been spared. I thought I'd grow old with him, but he just didn't hit the right part of the wave, I guess."

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