Issue 20 David Ho, M.D.,Scientific Director & Chief Executive Officer at ADARC

December 2019

Scientific Director and Chief Executive Officer, Aaron Diamond AIDS Research Center (ADARC)

Irene Diamond Professor, The Rockefeller University

Dr. Ho, you are a world-renowned physician at the forefront of medical innovation with HIV/AIDS Research. Can you share with our readers what motivated you to attend medical school and become a physician? Also, what event in your career or philosophical reflection drove you to specialize in HIV/AIDS research?

Dr. Ho with Irene Diamond, the philanthropist who created the Aaron Diamond AIDS Research Center; 1991

In 1970, I started in college as a student interested in physics. As I took courses in biology, however, I realized that the life sciences were undergoing a major transformation with a series of important discoveries. Gradually, my interest evolved to focus on biology, with an eye toward diseases affecting human health. This was the reason that upon graduating from Caltech, I entered Harvard Medical School, although my main objective was medical research rather than the practice of medicine. Several years later, while serving as chief medical resident in a hospital on the west side of Los Angeles, I chanced to encounter cases of young gay men who presented to the hospital with a multitude of infections that suggested that their immune systems were severely impaired. In retrospect, these were among the earliest cases of AIDS reported to the CDC in 1981. This medical mystery piqued my scientific curiosity, which I have pursued ever since. Of course, I did not realize then that this nascent disease would ultimately become one of the worst pandemics in human history

We see that you have been devoted to medical research and education for over 30 years. What were some of the most memorable achievements during your professional life? Also, what were the most demanding obstacles you had to overcome during the path of your career, and how did you do it?

The most important contribution to AIDS research from my laboratory is the unraveling of the dynamics of HIV in infected persons. Analyzing patient data quantitatively, we were able to shatter the old notion that HIV infection was largely quiescent for a long period of time. Instead, we revealed that HIV was highly dynamic throughout the entire course of infection. Every day, billions and billions of new HIV particles are produced and then removed. Similarly, millions and millions of infected T cells become newly infected, which then die in short order. Associated with this extensive and continuous HIV replication is the rapid destruction of CD4 T cells that are so important in orchestrating our immune systems in fighting pathogens.

You and your colleagues discovered the innovative “AIDS cocktail”, a combination antiretroviral therapy. This discovery turned AIDS, a fatal disease with no cure, into a treatable disease with a significantly lower mortality rate. Can you share with our readers the background of this ground-breaking discovery? How did this finding affect the course of your research for HIV/AIDS? What lessons can other researchers learn from your experience, in AIDS and in other disorders?

Dr. Ho in ADARC Lab

From the understanding of HIV dynamics discussed above, we came to understand in great detail that the virus was mutating so rapidly that millions and millions of new variants were being produced each day inside the body of an infected person. Given such high mutation rates, we easily determined that, if the drugs were given individually, mutants would arise each day to continually resist our antiretroviral drugs. Even administering two drugs at a time was relatively easy for HIV to evade. However, our calculations also suggested that if we were to force the virus to make multiple key mutations simultaneously in one viral genome (to resist a combination of three or more drugs), the probability that resistance would develop was exceedingly low. This realization in 1995 led us to initiate three different trials of combination antiretroviral therapy in patients. Within a few months, we knew that our strategy was correct in that we were able to durably control HIV replication in our patients. We waited a year to be sure the good results could be maintained for that duration. Indeed, by the summer of 1996, I announced our results to the world at the International AIDS Conference held in Vancouver. That became the turning point of the AIDS epidemic when an automatic death sentence was transformed into a manageable disease. Gratifyingly, over 21 million individuals worldwide have benefited from such a treatment strategy.

Especially early on, AIDS research was stymied to some extent by the stigma associated with the behaviors that came to be associated with higher risk for contracting the disease. Was your own work ever hampered by this problem? Can you offer any insights for how to overcome such problems in the care and treatment of other patients likewise stigmatized?

"That became the turning point of the AIDS epidemic when an automatic death sentence was transformed into a manageable disease"

Dr. Ho with Dr. Gerald Friedland, Chairman of the Board, Aaron Diamonds AIDS Research Center at the National Portrait Gallery in Washington, D.C. 2017

It was certainly distressing to witness the stigma and discrimination endured by infected persons. The injustice was suffered at the hands not only of strangers but also of family and friends, and even health care workers. Just imagine dying from a lethal disease while being shunned by your loved ones! At the time, we could rely solely on science to argue that this disease is transmitted only by intimate contact such as sex and sharing of needles, and not by casual contact. It was not easy, but with the passage of time and accumulation of scientific evidence, much of the public (in the US) has become reassured by the lack of casual transmission of HIV. Around the globe, however, many remain ignorant about the basic facts on HIV/AIDS, resulting in persistence of stigma and discrimination against infected persons. Knowledge is power.

Dr. Ho with Magic Johnson and Bill Clinton at `The Inaugural Irene Diamond Gala Dinner in 2009

As the Scientific Director and CEO of the Aaron Diamonds AIDS Research Center (ADARC), please share with our readers the mission and goal of ADARC. Also, having been involved with the center since 1989, did you witness or initiate any major shifts in how ADARC pursues its goals?

Our institute came into being in 1989, and we had a singular mission of making scientific contributions that would be meaningful to controlling this epidemic. We have done so by focusing on important scientific topics that could have an impact on the lives of patients. We are now primarily working on how to develop new modalities to block HIV transmission. These include vaccines, antibodies, and long-acting antiretroviral drugs. In addition, while we have good therapies for patients, we still do not have a cure. Thus, the pursuit of curative strategies is another major focus for us. Lastly, starting in January, the Aaron Diamond AIDS Research Center will officially be a part of the Columbia University Vagelos College of Physicians and Surgeons. This transition will mark the second phase of our research institute.

You have been involved with the center and at the forefront of this field for three decades. As an eminent opinion leader of HIV/AIDS research, what do you think are current necessities and urgencies in the field? Also, what do you forecast the major changes would be in HIV/AIDS studies in the next 10 years? How does your projection affect your research?

The answer to this question is partially addressed above. Since this virus continues to spread, with over 1.7 million new infections worldwide each year, we need to come up with some effective ways to block HIV transmission. An effective vaccine is the ultimate solution. However, that task is daunting and likely to require many more years. In the meantime, we need to come up with strategies to contribute to the slowing of HIV spread. Most promising preventive approaches to date include the use of HIV neutralizing monoclonal antibodies or long-acting antiHIV drugs. Both of these areas are important to my group. I suspect that we will be making important progress on this front in the coming years.

Can you share your final remarks with our readers from around the world? Also, do you have any advice for physicians and healthcare professionals who wish to take part in medical innovation?

Dr. Ho featured as Time Magazine’s Man of the Year in 1996

Practicing doctors help patients each day, one at a time. That could be most gratifying. On the other hand, medical scientists could help many patients at once with a major breakthrough that comes once in a decade or a lifetime. That, too, is gratifying, of course. But the greatest reward day to day is the pursuit of new knowledge. One must have the passion, curiosity, and tenacity for solving the unknown and discovering the new.

David Ho, M.D.

Scientific Director and Chief Executive Officer,

Aaron Diamond AIDS Research Center (ADARC)

Irene Diamond Professor, The Rockefeller University

David Ho, M.D., is a medical doctor and HIV/AIDS researcher who has made many innovative contributions to the understanding and technological treatment of HIV infection. He is the Scientific Director and Chief Executive Officer of the Aaron Diamond AIDS Research Center (ADARC) and the Irene Diamond Professor at The Rockefeller University in New York City. Dr. Ho has been at the forefront of AIDS research for three David Ho, M.D. Scientific Director and Chief Executive Officer, Aaron Diamond AIDS Research Center (ADARC) Irene Diamond Professor, The Rockefeller University decades. He has published over 400 papers, enabling the scientific community to understand the mechanism of HIV replication. Dr. Ho pioneered the “AIDS Cocktail” of combination antiretroviral therapy, which allowed the control of HIV replication in patients. He has received numerous honors and awards for his scientific accomplishments. He is the recipient of 12 honorary doctorates, including those from Columbia University and Tsinghua University. Dr. Ho was Time magazine’s 1996 Man of the Year, and on January 8, 2001, he was presented with the Presidential Citizens Medal by President Clinton. He received his bachelor of science in physics with highest honors from the California Institute of Technology and an M.D. from the Harvard-MIT Division of Health Sciences and Technology. He completed his residency in internal medicine at Cedars-Sinai Medical Center, UCLA School of Medicine, and his fellowship at Massachusetts General Hospital and Harvard Medical School.

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