Author Topic: Experiment in Monkeys Raises Hopes for HIV cure  (Read 237 times)

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Experiment in Monkeys Raises Hopes for HIV cure
« on: October 17, 2016, 01:05:38 AM »

A new drug combination helped stave off a monkey version of HIV for nearly two years after stopping all treatments, raising hopes for a functional cure for HIV, U.S. researchers said on Thursday.

The treatment involved standard HIV drugs, known as antiretroviral therapy or ART, plus an experimental antibody that hits the same target as Takeda Pharmaceutical's Entyvio, a drug approved in more than 50 countries for ulcerative colitis and Crohn’s disease.

The findings, published Thursday in the journal Science, are promising enough that scientists at the National Institutes of Health, which funded the research, have already begun testing the Takeda drug, known generically as vedolizumab, in people newly infected with HIV.

“The experimental treatment regimen appears to have given the immune systems of the monkeys the necessary boost to put the virus into sustained remission," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious diseases, part of the NIH, who co-led the study.

Sustained remission - known as a "functional cure" - could have sweeping implications for people infected with the human immunodeficiency virus or HIV, which attacks the immune system.

Highly effective treatments known as antiretroviral therapy push the virus down to undetectable levels in the blood, but they must be taken every day over a person's lifetime to remain effective, said Aftab Ansari of Emory University School of Medicine who co-lead the study.

Ansari said the study was based on the understanding that in the early days of infection, HIV attacks a specific class of immune cells that congregate in large quantities in the gut. They theorized that if they could protect these immune cells, they could buy the immune system enough time to mount an effective response.

To do this, the team tested an antibody that blocks a protein called alpha-4/beta-7 integrin that HIV uses to attack immune cells in the gut.

For the study, they infected 18 monkeys with simian immunodeficiency virus or SIV, the monkey version of HIV. They then treated all of the animals with ART for 90 days, and, as it does in humans, the ART controlled the virus, reducing it to undetectable levels.

Antiretroviral drugs used in this stage of the experiment included Gilead's tenofovir and emtricitabine, sold in a combination drug for people as Truvada, and a Merck integrase inhibitor known as L-870812.

In 11 monkeys, the scientists then gave infusions of the antibody for 23 weeks, and seven monkeys got a placebo. Three of the 11 monkeys developed a reaction to the treatment and had to stop the therapy.

In the eight monkeys that got the treatment, six initially showed signs that SIV was rebounding, but eventually their immune systems were able to control the virus. In two others, the virus never rebounded. All eight have continued to suppress SIV to undetectable levels for up to 23 months after all treatment stopped. In the control group, SIV rebounded and all seven animals died.

The study did not look at whether the monkeys were still able to transmit the virus, but studies in people have shown that reducing HIV to undetectable levels cuts transmission rates by nearly 100 percent.

Ansari said the study is promising because it could eventually lead to a treatment for HIV in people that would not require a lifetime of ART therapy.

Scientists have recently focused on efforts to cure HIV, reducing the burden of lifelong treatment, but prior efforts have been frustrated by the HIV virus' ability to form hidden reservoirs that replenish the virus when treatments are halted.

In one dramatic case, Timothy Ray Brown, the so-called "Berlin patient," was cured of HIV after an elaborate treatment for leukemia in 2007 that involved the destruction of his immune system and a stem cell transplant from a donor with a rare genetic mutation that resists HIV infection.

Ansari cautioned that not all treatments that work in monkeys will work in people. He said the findings are still very early, and said many more experiments are needed to understand why the antibody protected the monkeys.

Still, he said Takeda's antibody vedolizumab is "identical" to the one the team used on the monkeys.

NIH researchers already have begun a study to see if a 30-week course of Takeda's drug vedolizumab is safe and helps control HIV when patients are temporarily taken off conventional ART treatments. Preliminary results are expected by the end of 2017 with further data becoming available into 2018.

If proven safe, the drug would need to be studied in larger trials to prove it is also effective.

Takeda spokeswoman Elissa Johnsen said the company is "pleased to support the trial and contribute to scientific discovery" but said it was too early to comment on future development plans.



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