Understanding post-viral sequelae through the lens of HIV

Medical workers working in conference room: © Africa Studio-stock.adobe.com

For IDWeek’s John Enders Lecture, Igho Ofotokun, MD, MSc, Grady Distinguished Professor of Medicine at Emory University School of Medicine in Atlanta, Georgia, presented a session, "Using HIV as a model to understand the post-acute sequelae of viral infections.” With equal measures of deep expertise and passion, Ofotokun summarized a career focused on understanding how viral effects linger after the acute phase of infection resolves.

The lecture paid homage to John Enders, PhD, the Nobel laureate who pioneered techniques for poliovirus cultivation. Ofotokun admired Enders for his “true embodiment of collaboration and team science,” and reminded listeners that Enders himself created a lasting paradigm for viral infection, including acute, latent persistent, and chronic persistent infection.

Ofotokun first drew parallels between HIV infection and post-viral syndromes, highlighting the enduring effects of viral infections after recovery. From cardiomyopathy linked to enteroviruses, to oncogenic transformations due to herpes viruses, he pointed out the similarity of these sequelae to long-COVID and age-related comorbidities in HIV.

Ofotokun's work, which he says is based in "science and serendipity,” stemmed from an observation in which studies investigating fat redistribution surprisingly suggested a high incidence of bone mineral loss in HIV patients. This revelation led to a string of comprehensive studies that elucidated the intricate balance between osteoclasts and osteoblasts and revealed a systemic interplay between the immune and skeletal systems. Throughout his work, Ofotokun seamlessly stepped between patient and mouse model, probing the intricacies of the immune dysfunction, ultimately determining that HIV inflicts bone damage by disrupting B cell function, and leading to signaling imbalance.

“But there are nuances,” noted Ofotokun, and it is not only HIV that poses a threat. While antiretroviral therapies have restored the lifespan of infected individuals, these medications have also been found to cause osteopenia. This led Ofotokun to explore the immune response to antiretroviral therapies, discovering a marked, irreversible increase in T cell-mediated bone resorption days-to-weeks after starting treatment for all antiretroviral therapies.

But in deep scientific understanding also comes potential interventions. Ofotokun shared that early studies suggest that zoledronic acid can prevent osteoclastic activity, advocating for more studies into the utility of this class of agents for HIV patients on antiretroviral therapy.

Ofotokun then shared that the signaling molecule of this story extends beyond bones, where it is also thought to involve other organ systems. Bridging past and present, he alluded to the parallels between his work into other age-related comorbidities in HIV and the recent challenges posed by the post-acute sequelae in COVID-19 patients.

In closing, Dr. Ofotokun expressed heartfelt gratitude for his mentors, colleagues, and family who fueled his journey. With over 200 peer-reviewed publications and numerous awards, his career speaks volumes about his dedication in this impressive body of work, showcasing the power of relentless, team-based, multi-faceted inquiry in medical science and patient care.

Reference
Ofotokun, I. Using HIV as a model to understand the post-acute sequelae of viral infections. IDWeek 2023. October 13, 2023. Boston, Massachusetts.