Monkey Study Hints at Drug-Free Suppression of HIV

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Scientists may have found a way to suppress an HIV-like infection in monkeys, without the need for ongoing drug therapy.

The researchers added antibody therapy to standard drug treatment given to macaque monkeys infected with simian immunodeficiency virus (SIV). After three months, the animals were taken off the drugs, but their viral levels remained low to undetectable — for close to two years.

Experts stressed that the animal findings need to be viewed with caution, and that many questions remain.

But, they were also hopeful this could lead to a therapy that frees at least some people from their HIV drug regimens.

An initial safety study has already started at the U.S. National Institute of Allergy and Infectious Diseases (NIAID).

The drug “cocktails” used to treat HIV — known as combined antiretroviral therapy (ART) — have changed the face of the HIV/AIDS epidemic in countries where they are widely available.

“ART is highly effective at keeping the virus at almost undetectable levels in the blood,” said the study’s senior author, Aftab Ansari. He’s a professor at Emory University in Atlanta.

“But,” he added, “there are still some major issues. One is that when patients stop ART, the virus comes roaring back. So they have to take the drugs every day for the rest of their lives.”

That means facing the risk of long-term side effects such as heart, kidney and liver disease, type 2 diabetes and bone density loss. And, Ansari said, people on ART eventually develop resistance to the drugs they are taking, and need to switch to others.

A therapy that could essentially send HIV into remission, and release people from a lifetime drug regimen, would be a major advance, Ansari said.

For this study, his team used an antibody that targets a protein on immune system T cells called alpha4-beta7 integrin. The protein helps T cells find their way to lymph tissue in the gut.

The gut is a major reservoir for HIV, and HIV infects T cells. So Ansari reasoned that if T cells could be blocked from flocking to the gut during the acute stage of HIV infection, the T cells might be protected.

The investigators found that the alpha4-beta7 antibody seemed to do more than that.

The researchers began treatment on 18 macaques that had been infected with SIV for five weeks. The animals spent three months on ART drugs; four weeks after starting ART, the animals also began receiving infusions of either the antibody or a “control” substance, every three weeks.

Drug treatment got the animals’ blood levels of SIV down. When drugs were stopped, the virus rebounded in the control group.

Monkeys treated with the antibody, on the other hand, showed a much different pattern: Six of the eight remaining in the study showed some resurgence in the virus, but it was contained within four weeks. The other two showed no SIV rebound.

No one knows whether the findings will “translate” to humans, Ansari said.

But, he added, a pilot study is under way at NIAID — taking advantage of the fact that there is already an approved drug that is a humanized analogue of alpha4-beta7.

The drug, called vedolizumab (Entyvio), is used to treat Crohn’s disease and ulcerative colitis — two diseases in which the immune system mistakenly attacks the lining of the gut.

“I think people with HIV can really find some hope in these findings,” said Marcella Flores. She’s the associate director of research for amfAR, the Foundation for AIDS Research.

The “good news,” she noted, is that vedolizumab already exists and can be readily tested.

But there are still plenty of questions, Flores cautioned.

A major one is whether the antibody can be helpful if it’s given after the acute stage of HIV infection — a point at which few people would know they have the virus.

Ansari agreed. “If people have been infected for years, will this work?”

Flores also noted that with antibody therapy, it’s possible for people to develop their own antibodies against the treatment. That happened in three monkeys in this study.

She and Ansari also pointed to an unexpected finding: It’s not clear how the antibody is working.

The idea behind the experiment was that the antibody would block “trafficking” of T cells into the gut, and prevent them from being infected and “adding fuel to the fire,” Ansari said.

But the researchers saw something else that was unexpected: The resident T cells in the treated animals’ guts actually expanded.

It’s not clear what is going on, Ansari said. But, he added, it’s possible that the antibody is somehow “rebuilding” the immune system.

Ansari also stressed that if the approach eventually pans out in humans, it would not be a “cure.” It would suppress HIV without drugs, but would not eliminate it, he said.

The study was published Oct. 14 in Science.

More information

The U.S. Department of Health and Human Services has more on HIV treatment.

Source: HealthDay

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