Aids drug trial gets under way
DR ANTHONY Fauci doesn’t get too excited about the results of animal studies, and he doesn’t make house calls.
But when a drug already taken by thousands of people for intestinal conditions appeared to control the monkey version of HIV, it got the attention of the National Institutes of Allergy and Infectious Diseases director.
Fauci hopped on a plane to Cambridge, US, to tell Japan’s Takeda Pharmaceutical Co’s US representatives that their drug may offer a dramatic advance in the fight against Aids.
Takeda’s drug suppressed the virus to undetectable levels in eight monkeys, some for two years. The findings raise hopes for a so-called “functional cure” – a treatment that puts the disease in sustained remission.
“The data was so dramatic,” said Fauci, who has made Aids research his life’s work.
The drug is one of several promising ideas heading into early-stage human trials, all seeking to help control the virus that causes Aids for extended periods without daily antiretroviral therapy (ART).
HIV once meant certain death. But, for more than half of the 36.7 million HIV patients around the world, ART transformed it into a chronic disease. Taken daily, ART suppresses the virus. But keeping up a daily medication regimen is difficult.
The drugs are expensive and toxic, causing nausea, fatigue and nerve problems in the short-term, and insulin resistance and other problems over time.
Only about a third of US patients take ART consistently enough to push the virus down to undetectable levels.
“We’re going to need other approaches,” says Dr Nelson Michael, director of the US Military HIV Research Programme at the Walter Reed Army Institute.
Much work has focused on the discovery of rare antibodies made by HIV patients that can neutralise several forms of the virus. One trial involving an antibody called PGT121, licensed by Gilead Sciences, reduced the virus to undetectable levels in 16 of 18 monkeys; the effect lasted for four months in three of them.
At Walter Reed, Michael is taking a different tack, testing whether a vaccine – being developed to prevent HIV infection – can fight off the virus in infected individuals.
Last month, Michael and researchers at Harvard’s Beth Israel Deaconess Medical Centre published the results of a monkey test of Johnson & Johnson’s HIV vaccine candidate called Ad26/MVA and Gilead’s experimental drug GS-986.
On its own, the vaccine had a modest effect. But it was more effective when it was given with GS-986, a so-called TLR-7 agonist that “kicks the immune system up to a higher gear,” Michael said.
All nine monkeys that got both treatments showed significantly reduced viral loads. In three, the combination therapy has kept the virus at bay for six months.
Human trials could begin within months, J&J’s chief scientific officer, Dr Paul Stoffels, said.
Takeda does not study HIV. But its researchers understood the basic science surrounding its drug Entyvio, an antibody engineered to attack a specific protein.
The drug, known generically as vedolizumab, is approved in more than 50 countries for ulcerative colitis and Crohn’s disease, which occur when the immune system attacks the intestines.
“Entyvio is a cell-trafficking molecule that affects immune responses,” Shetzline said.
“In this instance, the GI tract is what is harbouring this HIV cell population that needs to be cleared – at least that is what the monkey study implies.”
Takeda is providing the drug and supporting the pilot study. — Reuters