By Bob Roehr
Monkeys infected with SIV, the primate equivalent of HIV, were given a nine-month course of a monoclonal antibody while on antiretroviral therapy (ART), then all treatment was stopped. Two of the treated monkeys showed no rebound of the virus while the remaining 10 animals showed a “viral blip” before they naturally suppressed their virus to a very low level. Certain subsets of immune cells also were replenished.
A study using a human version of the antibody is already underway and results from those first patients should be known by late 2017 or early the following year.
Anthony Fauci ripped up his scheduled remarks to present a detailed look at the data in an opening plenary address (Oct. 17) at the HIVR4P — research for prevention — conference in Chicago. It was based on a paper published a few days earlier (Oct. 14) in the journal Science. (DOI: 10.1126/science.aag1276, the paper is not freely available.)
Fauci is perhaps the world’s best-known face of HIV research. He has headed up the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) since the start of the epidemic, making major contributions in his own lab and distributing more than $29 billion is HIV research funding, approximately half of all NIH funding on the disease since 1984.
The a4b7 monkey antibody the researchers created blocks a similarly named receptor that appears on the surface of CD4 and other immune cells. Normally the receptor is used to help guide immune cells to the gut, a central site of HIV infection. There were clues from other studies that a4b7 might be important, so Fauci thought it would be interesting to block the receptor.
“What was exciting about it was how profound the difference was between the two” groups of monkeys, Fauci later explained to reporters. All of the animals that received the antibody were able to control the virus once they stopped ART, while the animals that did not receive the antibody all got sick. The initial group of animals remains healthy about two years after stopping ART while a second group remains healthy after about a year.
Even before the paper was published, the NIH launched a proof of principle study in humans, enrolling the first of an estimated 15 to 25 patients. (https://clinicaltrials.gov/ct2/show/NCT02788175?term=vedolizumab+hiv&rank=1)
It is using vedolizumab (trade name Entyvio), a human anti-a4b7 monoclonal antibody that was approved by the FDA in 2014 to treat the irritable bowel diseases (IBD) ulcerative colitis and Crohn’s disease. Fauci said the Japanese firm Takeda Pharmaceuticals has been “incredibly easy to work with” in terms of sharing data and preparing for the study of vedolizumab.
“I have to emphasize over and over again that we don’t know what the mechanisms” of action are — how or why it works — “but it is loud and clear what the effect is.” Fauci said, “I would not be surprised if we found out it was a different mechanism” from that seen with IBD.
Chicago HIV prevention activist Jim Pickett expressed the ambivalence of many who heard the presentation. While a “functional cure” for HIV would be warmly embraced, they don’t want to raise false hopes within the community for something that may not pan out, and if it does, is likely to require many more years of research.
:If monkeys were perfect predictors, then we would have an HIV vaccine by now,” cautioned Kenneth Mayer, director of research at Fenway Health in Boston.