(Bloomberg) — Two decades ago, Gus Cairns was certain AIDS would kill him. He had buried his partner and seen countless friends succumb to the disease. Cairns was constantly tired, he lost 35 pounds because he couldn’t keep food down, and he suffered from chronic stomach bugs. 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 café 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. Some 36 percent of HIV-positive adults in developed countries are now 50 or over, up from 13 percent in 2000, according to UNAIDS. 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 not only for the virus, but also for the people who take them. That poses a new challenge for drugmakers: 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 so-called combination therapies, where three or more drugs attack the virus so it has a harder time developing resistance. For nearly a decade, Truvada from Gilead Sciences Inc. has been the preferred basis of therapy, but it’s known for harsh side effects such as kidney damage and loss of bone density — concerns that are typically even worse for older patients.
GlaxoSmithKline Plc — the company that created the first HIV drug, AZT — is now working on two-drug combinations. In 2013, Glaxo introduced a new treatment that scientists say is less toxic than older formulas and which makes it hard for the virus to evolve resistance. Though the drug, called Tivicay, is usually used in combination with other medications — often including Truvada — researchers say it could become the foundation of simpler two-drug regimens.
The drive to simplify treatment could dramatically rearrange the competitive landscape. As word of Tivicay spread, Glaxo in 2014 made small gains in market share, 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 & Co. and Pfizer Inc. that makes HIV treatments. Two-drug regimens, rather than today’s three-drug cocktails, “would mean less product in the body, better profile, and potentially less cost.’’
Gilead this year received Food and Drug Administration approval for an upgraded version of Truvada that replaces the ingredient connected to kidney and bone problems with a formulation that causes fewer side effects. The company says it has introduced two new 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.
For a QuickTake explainer on access to medicines in poor countries, click here.
The growing numbers of HIV patients over 50 could benefit from simpler treatment options. As infected people reach retirement age, their medical regimens become more complex because of viral resistance combined with health problems related to aging.
“It gets complicated as you get older,” says Caspar Thomson, executive director of NAM/Aidsmap, a 30-year-old information portal on HIV.
Tivicay belongs to a new group of drugs called integrase inhibitors that can prevent HIV 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 Tivicay and similar compounds block that process.
Shionogi was a pioneer of these treatments, and the Japanese drugmaker’s work soon drew Glaxo’s attention. The companies set up a partnership in 2001, giving Glaxo access to groundbreaking research at a time when its new-drug pipeline was weak. Shionogi benefited by tapping into Glaxo’s global sales network and its worldwide research operation — important because Japan didn’t have enough HIV patients for human trials of the drugs.
The companies say they evaluated over 4,000 compounds, but rejected the vast majority long before they made it to human trial. And even the handful tested on humans ran into a host of problems. An early version showed promise in test tubes, but failed in human trials because it got broken down too quickly in the body. Another stalled after it was shown to cause liver problems in monkeys.
Then in November 2007, the research team hit upon a compound that worked in the lab and in healthy subjects. A few months later, they tried it on HIV-infected patients, and after 10 days of treatment their viral loads had plunged. That was the compound that became Tivicay.