Experiment in monkeys raises hopes of 'functional cure' for HIV

17 Oct, 2016

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 theorised 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.
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.

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