HIV Lymphocyte Dynamics and Implications for Therapy
David Ho, Founding Scientific Director and Chief Executive Officer of the Aaron Diamond AIDS Research Center; ; Irene Diamond Professor at The Rockefeller University
Description: Few researchers become legends in their own time, but David Ho's relentless quest to understand and conquer the AIDS virus has earned him worldwide renown. He elucidates the approach his lab has taken in the last decade to understanding how HIV replicates in cells, and how effective drugs have been developed to stymie the progress of the virus once a patient is infected. Within weeks of contracting HIV, there is exponential growth of the virus, which peaks swiftly, followed by a long period where the number of virus particles produced equal the number of particles cleaned out by a patient's liver and spleen. There's a "steady flow out and a steady flow in," says Ho. During this period, which might last 10 years, the virus may not cause symptoms, but it steadily depletes the patient's supply of a type of crucial immune cell.
Ho's research in the 1990s took a quantitative approach to the dynamics of viral infection. By using a drug that helped block the reproduction of the virus, Ho discovered that virus replication and clearance happened very swiftly. "Half of what's in circulation is removed in a half-hour, to be replaced by an equal amount of virus." He also measured the total virus production per day, which for an average patient, meant somewhere between 1010 and 10 12 virus particles.
Ho says that one of the implications "of this relentless replication at very high levels" is a high mutation rate. HIV can shape shift and evade control by a single drug. Ho's research helped generate the AIDS cocktail -- multiple antiretroviral drugs to block the progression of HIV at different points in its replication cycle.
While these therapies have diminished the AIDS mortality rate, mainly in western nations, Ho hopes to slow the spread of HIV worldwide, especially in parts of Africa where it continues to grow exponentially in the population. A vaccine that could "put more pressure on the virus," at the earliest days of infection, could potentially "cause a shut off of infection and abolish it from taking hold."
About the Speaker(s): David Ho has been actively engaged in AIDS research for 24 years, and has published over 350 papers on the subject. He received his degrees from the California Institute of Technology (1974) and Harvard Medical School (1978). Subsequently, he did his clinical training in internal medicine and infectious diseases at Cedars-Sinai Medical Center/UCLA School of Medicine (1978-1982) and Massachusetts General Hospital/Harvard Medical School (1982-1985), respectively. Ho has received numerous honors and awards for his scientific accomplishments. He was named Time Magazine's Man of the Year in 1996, and was the recipient of a Presidential Medal in 2001. He has been elected as a member of the American Academy of Arts and Sciences, Academia Sinica (Republic of China), Chinese Academy of Engineering, and the Institute of Medicine, National Academy of Science in the United States. Ho served on the Board of Overseers of Harvard University, and he currently sits on the Board of Trustees of the California Institute of Technology, and Board of the Massachusetts Institute of Technology Corporation.
Host(s): School of Science, Harvard-MIT Division of Health Sciences and Technology
Tape #: T21078
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