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Lab Spotlight - Susan Koletar, MD

Raising Awareness: HIV/AIDS VideoWith a small ironic laugh, Susan Koletar, MD, director of Ohio State's Division of Infectious Diseases in the Department of Internal Medicine, recounts how she was "pretty sure" the first reports in 1981 of a cluster of men with a rare opportunistic infection and no known cause of immunosuppression would have no impact on her career. As a medical student when AIDS was first observed in the United States, she had broad interests in almost all medical fields. By the time she finished her fellowship in infectious diseases at The Ohio State University in 1987, however, she found herself working in the middle of a new epidemic that set the course of her career as a clinician specializing in HIV.

Dr. Koletar came to The Ohio State University with the goal of studying opportunistic infections in immunocompromised transplant patients. When HIV-positive patients began appearing in the Midwest, she started her research on thrush, an oral fungal infection common at that time in the population. Koletar's research was part of the early efforts, in those grim times, focusing on controlling and preventing the opportunistic infections that quickly killed those infected with the virus. The young clinician began working with Robert Fass, MD, the director of the AIDS clinical trials unit (ACTU), the federally funded grant that supports a wide variety of AIDS clinical trials. She took over as the principal investigator at Ohio State in 2002.

A review of the subjects of Dr. Koletar's clinical trials over her career tracks the progress against HIV. As antiretroviral (ART) therapy was developed to directly treat the HIV infection, trials designed to test the drugs and administration of the drugs were added to her repertoire. Now, HIV infection in the United States can be treated as a chronic problem. Koletar notes that mathematical models predict that an individual infected with HIV at age 25 who receives regular care and treatment has a life expectancy only four months shorter than normal. Her clinical research now focuses on what seemed like an unlikely set of problems only a few years ago—chronic illnesses.

If understanding chronic illnesses such as kidney and heart diseases or osteoporosis in patients not infected with HIV, it is much more so in the HIV-positive population. Koletar lists the complicating factors: chronic inflammation from constant low-grade viral load, high smoking rates among the HIV-positive population, side effects from decades of ART treatment, and interactions between ART therapies and drugs used to treat chronic illness. Among the clinical trials she is conducting are those that begin to address treatment of bone loss and heart disease in the HIV infected population.

One trial close to finishing accrual at Ohio State is the START trial, which addresses treatment of HIV more directly. START is designed to test whether it is best to begin ART therapy when the count of CD4 cells, the lymphocytes that are directly infected by HIV, drops to a certain threshold or when it is discovered that the patient is infected by HIV. HIV-positive individuals may not have lowered CD4 counts for a long period of time after infection. Keeping the viral load very low by treating immediately may lead to better outcomes, but committing to drug therapy sooner in life may lead to chronic side effects such as kidney or heart disease. It also means that patients need to commit to the drug regimen for more of their lives. Koletar notes that stopping therapy once it has begun is dangerous, leading to drug resistance and poor health outcomes. Given that many of the newly infected patients Dr. Koletar now sees are young—in their 20s—this is not a small commitment, even if the famously complex drug cocktails of the early days of ART therapy have given way to pills combining drugs,  thus simplifying  treatment regimens.

Another promising trial in Koletar's profile is one testing a therapeutic vaccine against HIV. Most are familiar with preventive vaccines, those administered to confer immunity from a disease such as measles. Therapeutic vaccines, on the other hand, are designed to boost the body's natural immunity so it can control the virus more effectively, allowing the infected individual to go extended periods of time without medication. It is hoped this can lead to improved compliance with a reduced drug regimen, a reduction in side effects, fewer drug-drug interactions—and perhaps a lower viral load in an entire populations, which could lead to fewer infections.

Through all the clinical research she conducts, Dr. Koletar remains passionate about her patients. She fears for the generation of young people who have an "It's just HIV and it's treatable" attitude and expresses sorrow at the number of very young people she is seeing in the clinic who are newly infected. Although treatable, her own experience in research shows how different a life lived with HIV is from a normal life.