Frank J. Palella Jr., Ph.D., affiliate faculty member at ISGMH and professor of medicine in the Division of Infectious Diseases at Northwestern University, presented on his work on January 21 as part of ISGMH’s annual Affiliate Showcase.
Palella’s lecture on “Lessons Learned from HIV Observational Cohorts” emphasized the power of observational data in HIV/AIDS research by outlining specific research studies that greatly impacted the ways healthcare providers have treated HIV/AIDS over the last four decades. Palella argued that observational research, which involves observing individuals and measuring their health outcomes without providing any interventions, is an excellent way to study dangerous exposures. “If you suspect something—a practice, a drug—will pose a health risk, you can’t conduct a trial in which you expose someone willingly to that. But if it involves a practice or exposure that is common enough, you can study people at highest risk for exposure,” explained Palella. Such research first linked cigarette smoking to lung cancer and high cholesterol to heart disease. In the 1980s and 1990s, observational research proved crucial in addressing prognostic factors and effective therapy interventions for HIV/AIDS.
Major observational cohort studies created in the 1980s and 1990s, such as the Multicenter AIDS Cohort Study and the HIV Outpatient Study (HOPS), helped to identify prognostic factors in HIV/AIDS, which are measurements to predict one’s health and optimize effective treatment. First established in 1983, the Multicenter AIDS Cohort Study is the longest ongoing natural and treated history study of HIV infection in the world. Its original cohort included both HIV-infected and uninfected men who have sex with men (MSM), which provided a naturally occurring control group for researchers to analyze. Through this cohort, Palella and his colleagues were able to show in the collected data that both an individual’s CD4 cell count, the number of white blood cells that fight infection, as well as their viral load, the amount of HIV in an individual’s blood, were important prognostic factors for which HIV-positive individuals presented symptoms or not.
The HOPS study involved 10 sites of care across seven U.S. cities, with over 11,000 participants enrolled from 1993 through 2018. With the advent of Highly Active Anti-Retroviral Therapy (HAART therapy) in 1996, Palella and his colleagues observed dramatic and then sustained declines in mortality and morbidity rates in this cohort. “All it took was 1 to 1.5 years of data” to illustrate this effect, Palella said. This research led Palella and his team to write the lead article in The New England Journal of Medicine (NEJM) in 1998, which concluded that the declines in morbidity and mortality due to AIDS were attributable to the use of more intensive antiretroviral therapies. The article remains one of the most highly cited papers in the history of the HIV epidemic.
After the HOPS study, HIV’s next research focus centered on when therapy should begin for an HIV-infected person. Palella began by looking at patients whose providers initiated therapy at different CD4 cell count levels. It had been argued at the time that, because of the purported toxicity of HAART therapy, treatment should be reserved for patients whose white blood cell count dropped below 200. Through the HOPS study, however, Palella and his colleagues were able to show that waiting to treat patients until their white blood cell count was below 200 resulted in four times as much death. Additionally, this data provided the first hint that having higher cell counts in the 350-500 range could actually be beneficial for fighting infection. “The observational data on mortality, survival, and other diseases showed that intervening with therapy as soon as a patient is diagnosed is the best possible path forward,” Palella said. Starting therapy as soon as HIV is diagnosed remains a best practice today.
Nanette Benbow also presented at the Affiliate Showcase on what it takes to create meaningful public-academic health partnerships. Read about her talk here.