Mark D. Hicar, MD, PhD, assistant professor of pediatrics, has been awarded a five-year, $1.9 million grant from the National Institute of Allergy and Infectious Diseases to investigate why some people infected with the HIV virus do not develop AIDS.
Unlocking the Key to Long-Term Nonprogression
Called “long-term nonprogressors,” these people make up about 1 percent of the world’s population. Scientists have studied them extensively, but the specific mechanism of their survival remains a mystery.
“People have been studying this population, but there has not been a definitive explanation of why they do well without therapy,” says Hicar, the grant’s principal investigator.
Despite the fact new medicines have helped turn AIDS into a chronic disease that can be managed, the drugs are expensive and widely available only in the developed world. AIDS remains a global threat with 40 million to 50 million active infections worldwide.
Identifying the mechanism that allows people to live with HIV without medication could lead to new medicines for people with the virus or even a vaccine.
Discovering Uncharacterized Targets for Antibodies
Hicar holds a doctorate in molecular virology, immunology and medical genetics and 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.
A pediatric infectious disease physician at Women and Children’s Hospital of Buffalo, Hicar 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 previously 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.
Study Focuses on Three Groups of People with HIV Virus
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 viruses.
“It isn’t clear precisely how they work,” he says, but finding how they function is another aim of the study.
To discern if targeting these sites truly correlates with long term non-progression, he will use the grant to study three groups of people with the HIV virus:
- long-term nonprogressors
- regular progressors
- people whose immune system has recovered while taking medication