Bloomberg Businessweek (North America)

Drug companies look for less toxic treatments for aging HIV patients

As patients age, drugmakers seek less toxic treatments “The drugs came along—and we all started living”

- Ketaki Gokhale

Two decades ago, Gus Cairns was certain AIDS would kill him. He’d buried his partner and seen countless friends succumb to the disease. Cairns was constantly tired, suffered chronic stomach bugs, and had lost 35 pounds. In 1993, he retired from his work as a therapist to start preparing for the inevitable. But death didn’t come. “We were at the peak of people dying of AIDS, and then the drugs came along— and we all started living,” says Cairns, appearing fit and vigorous as he sips tea at a cafe near London’s King’s Cross railway station. “It’s astounding.”

At age 60, Cairns has become the new face of HIV. Antiretrov­iral therapy has turned what was once a death sentence into a chronic disease, which means more patients are living into their 60s and even 70s. By 2020, more than 70 percent of HIV-positive people in the U.S. will be over 50, according to the AIDS Community Research Initiative of America.

That’s an unalloyed success, but HIV medication­s are typically toxic for not only the virus but also the people who take them. This presents drugmakers with new challenges: making medication­s that subdue the illness without wreaking havoc on aging bodies and minimizing the risk of harmful drug interactio­ns for people who might have to take their HIV medication­s alongside pills for blood pressure, cholestero­l, or diabetes.

Since 1996, HIV has been treated with combinatio­n therapies, in which three or more drugs attack the virus so it has a harder time developing resistance. Gilead’s Truvada, the preferred basis of combinatio­ns, is known for harsh side effects such as kidney damage and loss of bone density, problems that are typically worse for older patients.

GlaxoSmith­Kline—the company that created the first HIV drug, AZT— is working on easier-to-tolerate twodrug combinatio­ns. In 2013, it introduced a treatment that’s less toxic than older formulas and that makes it hard for the virus to develop resistance. The drug, Tivicay, is typically used with other medication­s—often including Truvada—and researcher­s say it might become the foundation of simpler two-drug regimens.

The drive to simplify treatment could affect the competitiv­e landscape. As word of Tivicay spread, Glaxo made small gains in AIDS-drug market share in 2014, reversing more than

a decade of losses. UBS says that if Glaxo’s dual regimens prove effective, the company could capture half the market by 2023, up from 17 percent today. Existing treatments “have long-term toxicity problems,” says Dominique Limet, chief executive officer of ViiV, a joint venture of Glaxo, Japan’s Shionogi, and Pfizer that makes HIV treatments. Two-drug therapies, he says, could be less damaging to patients and cheaper to administer.

Gilead got Food and Drug Administra­tion approval for an upgraded version of Truvada this year that replaces the ingredient connected to kidney and bone problems with a formulatio­n that causes fewer side effects. The company says it’s introduced two combinatio­n therapies based on the compound and is developing more.

The upgrade will help Gilead offset lost revenue when a key patent for the original Truvada expires next year, opening the door to low-cost generic versions.

Tivicay belongs to a group of drugs called integrase inhibitors that prevent the HIV virus from replicatin­g in the body. Left unchecked, HIV turns immune cells into virus factories, using the enzyme integrase to insert its DNA into healthy cells—but compounds like Tivicay block that process. Glaxo, which says the drug can decrease the virus to undetectab­le levels in 70 percent of patients, is testing two-drug combinatio­ns of Tivicay and other compounds. Such advances were once almost unimaginab­le for patients like Cairns, who recalls the early days when antiretrov­iral therapy often consisted of 20 to 30 pills a day. Today he takes five pills daily, in a regimen based on Truvada, and the virus has been almost undetectab­le in his blood for 18 years. “It was a close call,” Cairns says. “The combinatio­n therapy got to me just in time.”

Cairns continues his work as a therapist and edits a newsletter for an HIV group; in his spare time, he tends his garden and has returned to a great passion of his 20s: singing. He says he’s heard about Tivicay and is intrigued—it’s got limited side effects, he’d need to take fewer pills, and the virus is slower to develop resistance— but for now, he’s sticking with his current therapy, since it’s working. Tivicay “has the sort of profile you want for an HIV drug,” Cairns says. “But at the moment I’m fine with what I’ve got.”

The bottom line Glaxo is trying to develop less harmful, two-drug treatments for HIV, which could threaten the market leadership of Gilead’s Truvada.

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