"It's sobering": A formerly exciting HIV cure strategy fails in humans | Science

By Jon Cohen Jul. When Science published a monkey study almost 2 years ago that showed an anti-inflammatory antibody effectively cured monkeys intentionally infected with simian form of the AIDS virus, the spectacular results have turned many heads. But some skeptical researchers felt that the data seemed too good to be true and predicted that the intervention would not work on HIV in humans. They were right.

Anthony Fauci, head of the US National Institute of Allergy and Infectious Diseases and co-author of the article Science reported today the failure from a clinical trial that was trying to translate remarkable monkey success to humans. "We have not seen these dramatic results at all," Fauci told the International AIDS Conference in Amsterdam this week.

In the monkey experiment, animals infected with simian immunodeficiency virus (SIV) were treated with antiretroviral drugs (ARVs) that suppressed the pathogen, then given repeated injections of 39, an antibody that blocks a receptor called α4β7 found on immune cells. The researchers then stopped giving both the antibodies and the ARVs, and the monkeys still completely controlled the SIV for more than 9 months. The virus quickly returned to control animals that had received only antiretrovirals, and this treatment was discontinued. Some considered that the antibody-treated monkeys were cured because they seemed able to control indefinitely the small amount of virus that persisted without further intervention.

In the human study, Fauci and his colleagues recruited 18 people who were all on antiretrovirals and had undetectable levels of HIV in their blood for at least 2 years. For 30 weeks, participants received 9 infusions of vedolizumab, a monoclonal antibody that binds to α4β7 and is on the market to treat Crohn's disease and ulcerative colitis (which was slightly different from the previous one). antibody received by monkeys)

is found on the surface of CD4 white blood cells, the preferred target of HIV. The Fauci group had already shown in test tube experiments that white blood cells strewn with both α4β7 and CD4 are much more sensitive than other cells to HIV infection. . If people reacted like monkeys to antibody therapy, once vedolizumab blocks α4β7, they could stop antiretroviral drugs and HIV that would inevitably remain would copy itself, but would have trouble infecting cells. and to create new virions

. case, Fauci explained. In all 18 but two people, HIV returned after stopping ARVs. In addition, a team of researchers who were not involved in the original study on the monkeys tried to repeat it in another group of primates, and they reported at the meeting that their experience n & # 39; Had not succeeded. The original monkey results, Fauci said, "could be a stroke of luck."

Kenneth Mayer, a prominent HIV / AIDS clinician who is the director of medical research at the Fenway Institute in Boston, called the results "sober." And more, the vedolizumab joins a long list of other potential HIV cure strategies that have yielded exciting initial results, but which, once put to the test in the real world, have become kaput.