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Study of those who survive with HIV, without medicine, could yield medicine for those who do not

University at Buffalo doctor receives federal grant to study ‘long-term nonprogressors'

By Grove Potter

Release Date: May 5, 2017

“People have been studying this population, but there has not been a definitive explanation of why they do well without therapy.”
Mark Hicar, research assistant professor in pediatrics
Jacobs School of Medicine and Biomedical Sciences

BUFFALO, N.Y. — A small percentage of the world’s population ­— about 1 percent — can be infected with the HIV virus but not progress to AIDS, and researchers do not know why.

Called “long-term nonprogressors,” these people have been studied extensively, but the specific mechanism of their survival remains a secret.

A University at Buffalo faculty member and researcher has been awarded a $1.9 million, 5-year grant from the National Institute of Allergy and Infectious Diseases to look into that mystery.

“People have been studying this population, but there has not been a definitive explanation of why they do well without therapy,” said Mark D. Hicar, MD, PhD, research assistant professor in pediatrics in the Jacobs School of Medicine and Biomedical Sciences, and the grant’s principal investigator.

HIV and AIDS research has fallen from the headlines in America, in part, because new medicines have helped turn AIDS into a chronic disease that can be managed. But those drugs are expensive and widely available only in the developed world. Across the world, AIDS is still on ongoing issue, with 40 to 50 million active infections.

So it remains a global threat.

Hicar, also a pediatric infectious disease physician at Women and Children’s Hospital of Buffalo, is continuing work he started during his fellowship. He is looking into a group of 100 antibodies culled from a group of long-term nonprogressors. From this collection, he has discovered previous uncharacterized targets for antibodies on the gp41 section of the envelope protein on the surface of the virus.

Hicar discovered that, compared to those that progress to AIDS, other populations of long-term nonprogressors are also enriched for antibodies that target these specific sites. It’s possible that antibodies similar to those in his collection are key to how someone becomes a long-term nonprogressor.

Most antibodies help to shuttle viruses and bacteria to other immune cells that gobble them up. The antibodies in Hicar’s collection don’t seem to function in the normal manner of antibodies that neutralize virus. “It isn’t clear precisely how they work,” he said, but finding how they function is another aim of the study.

Hicar is an MD and has a PhD in immunology. As a student, he was interested in the DNA structure of how antibodies are built, and wanted to study the targets of antibodies in infectious diseases.

With the grant, he will study three groups of people with the HIV virus: long-term nonprogressors, regular progressors and people who have recovered while taking medication to discern if targeting these sites truly correlates with long term non-progression.

If Hicar has identified the mechanism that allows people to live with HIV without medication, it could lead to new medicines for people with the virus or even a vaccine.

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