Showing posts with label immune. Show all posts
Showing posts with label immune. Show all posts

Thursday, 24 October 2013

Immune Protein Found to Block HIV Spread in Some People

News Picture: Immune Protein Found to Block HIV Spread in Some People

WEDNESDAY, Oct. 16 (HealthDay News) -- One percent of people infected with HIV have a second line of defense deep in their immune system, which serves as a back-up for the body's defenses that get wiped out by the virus, according to a new study.

These people, known as "controllers," are able to maintain long-term control of HIV without a daily regimen of antiviral medication because of a defensive immune protein, known as A3, which blocks the virus from spreading throughout their body.

Scientists from Northwestern University suggested their findings could help shorten the drug treatment required for others who have HIV, the virus that causes AIDS.

"Preserving and even increasing this defense in cells may make more HIV-infected persons into controllers and prevent HIV from rebounding to high and damaging levels when anti-HIV medications are stopped," the study's senior author, Dr. Richard D'Aquila, director of Northwestern's HIV Translational Research Center, said in a university news release.

In conducting the study, published online Oct. 16 in PLoS ONE, the researchers analyzed the cells of controllers in a lab. They found that these rare individuals have a greater supply of the A3 protein in specific white blood cells called resting memory T cells. Any new HIV made from those cells is rendered harmless by A3 and is unable to infect other cells.

Unlike other cells in the immune system that are unable to recognize HIV once it mutates, A3 is part of the so-called intrinsic immune system that isn't fooled by the virus. "The intrinsic immune system recognizes the basic guts of the virus -- the nucleic acids -- that HIV can't change and then damages those nucleic acids," D'Aquila explained.

The researchers suggested that earlier treatment could help others eventually maintain control of their HIV without medication by protecting their reserves of A3.

"Perhaps starting anti-HIV drugs very soon after HIV is caught, rather than the current practice of waiting until later to start, would work like the controllers' first line of defense," D'Aquila said. "If we preserve A3, it could minimize HIV's spread through the body as this protein seems to do in controllers."

The researchers noted there are several cases of early HIV treatment resulting in long-term control of the virus. For example, in January 2013, a baby born to an HIV-positive woman became infected with the virus but was given anti-HIV drug treatment within 36 hours of birth. That baby is now off antiviral medication and apparently cured of HIV, D'Aquila said.

If HIV remains unchecked for several months, however, the researchers suggested reserves of A3 are simply wiped out. They are currently working to develop a drug that would boost the A3 protein.

"Early-as-possible detection -- much easier with our new technology -- and early drug treatment will be the future of HIV therapy," D'Aquila concluded. He added that the new U.S. health law, the Affordable Care Act, now requires insurance companies to pay for routine HIV testing.

-- Mary Elizabeth Dallas MedicalNews
Copyright © 2013 HealthDay. All rights reserved. SOURCE: Northwestern University, news release, Oct. 16, 2013



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Friday, 5 July 2013

Early HIV Treatment Restores Immune System (CME/CE)

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Published: Jul 5, 2013

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.Note that this prospective cohort study demonstrated superior HIV control and CD4 counts among patient initiated on HIV therapy prior to achieving CD4 counts <500/mm3 -- adding to the potential value of earlier initiation of therapy.Be aware that the study findings may reflect inherent differences between those with higher baseline CD4 counts and those with lower baseline CD4 counts as it lacked an adequate control group.

KUALA LUMPUR -- Antiretroviral therapy can restore aspects of a normal immune system in some patients with chronic HIV, as well as reduce the size of the viral reservoir, a researcher said here.

The catch is they have to start with a relatively intact immune system, with at least 500 CD4-positive T cells per microliter of blood, according to Laurent Hocqueloux, MD, of the Centre Hospitalier Régional in Orleans, France.

But the finding, from a prospective observational cohort study, suggests such patients might be most likely to benefit from future interventional trials aimed at eradicating the virus, Hocqueloux argued at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.

Hocqueloux and colleagues have previously shown that treatment early in HIV infection leads to a weak viral reservoir and a good restoration of the immune system.

In some patients treated very early, that has led to what the researchers are calling "post-treatment control" -- the ability to go off HIV therapy without having the virus resume growing in the body.

But, Hocqueloux said, they wondered if some patients who had reached what is considered chronic infection might also see immune restoration and a weak viral reservoir.

To find out, they studied 309 patients treated with antiretroviral drugs from 2005 through 2012 and asked what proportion would regain a normal CD4 count of at least 900 cells, a normal ratio of CD4 to CD8 cells of more than 1.0, and fewer than 2.3 log10 copies of HIV DNA per million peripheral blood mononuclear cells (PBMCs).

Patients were stratified by their lowest CD4 count before starting therapy -- fewer than 200, 200 to 499, and 500 or more.

At study entry, Hocqueloux reported none of the patients met the primary endpoint.

But after 4 years of treatment, 30% of those who started with more than 500 cells did so, compared with 7% of those in the middle category, and 2% of those in the lowest group. The trend was significant at P=0.0001.

Patients who started with 500 of more CD4 cells wound up with a median count of 1,100 cells, a CD4/CD8 ratio of 1.25, and an HIV DNA load of 2.51 log10 copies per million PBMCs.

Those who started with fewer than 500 cells were significantly worse on all three benchmarks, Hocqueloux said.

He cautioned that the study had a cohort design, had short follow-up, and still needs to be confirmed in other cohorts.

But at a minimum, the study confirms the value of early treatment, before the immune system is too badly degraded, he said. And the findings may point toward good candidates for trials of therapeutic vaccines or strategies aimed at "emptying" the viral reservoir and leading to remission.

Indeed, the study found a "very dramatic difference" between those with high and low initial CD4 counts in terms of the outcome of therapy, commented Robert Murphy, MD, of Northwestern University Feinberg School of Medicine in Chicago.

But patients who met the study's endpoint are unlikely to be able to control the virus on their own, without the aid of HIV therapy, because they are already chronically infected, Murphy told MedPage Today.

Still, he agreed with Hocqueloux that they might be the best choices for proof-of-concept studies aimed eradicating the viral reservoir, he said. "To prove the concept," he said, "you have to pick the patients most likely to succeed and these are those patients."

For that reason, he added, "this is a really, really important study."

The study was supported by the French national AIDS research agency. Hocqueloux did not make any financial disclosures.

Murphy reported financial links with Gilead.

Primary source: International AIDS Society
Source reference:
Hocqueloux L, et al "In chronically HIV-1-infected patients long-term antiretroviral therapy initiated above 500 CD4/mm3 achieves better HIV-1 reservoirs' depletion and T cell count restoration" IAS 2013; Abstract WEAB0102.

North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers' Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.