HIV Science: Dynamic, Inspiring

Attending the Conference on Retroviruses and Opportunistic Infections (CROI) this year was, as always, an inspiring experience. The sheer breadth of groundbreaking research presented reaffirmed that the field of HIV science remains dynamic, innovative, and deeply committed to finding a cure. Among the many fascinating talks I attended, three stood out for their potential to reshape our understanding of how we might one day achieve long-term HIV remission without lifelong antiretroviral therapy (ART).

While we have long understood the importance of HIV-specific CD8⁺ T cellsin fighting HIV in lymph nodes, a study presented by Dr. Andrea Mastrangelo (University Hospital, Lausanne, Switzerland) took a deeper dive into how these cells function in individuals who naturally control the virus without medication—so-called “HIV controllers.” Dr. Mastrangelo’s research revealed that these individuals’ T cells exhibit a unique, stem-like quality that allows them to renew themselves and they appear to be able to evolve with time, suggesting a dynamic adaptation of the immune response. These findings underscore the importance of targeting lymph node-resident immune cells in future cure strategies, offering new hope for approaches that harness the body’s own defenses to suppress the virus.

Another interesting study focusing on lymphoid tissues was presented by Dr. Amare Eshetu (Yale University). Using an advanced approach known as spatial transcriptomics, Dr. Eshetu and colleagues identified distinct immune environments within these tissues that support HIV persistence. Interestingly, they found that in viremic individuals (those with active HIV replication), certain immune cells exhibited a genetic signature typical of both a strong antiviral response and exhaustion. In addition, these cells appear to express BACH2 and BCL2AT genes, possible markers of long-term survival. In contrast, in virally suppressed individuals, only minimal antiviral responses were detected. Understanding these immune landscapes may be key to developing therapies that can effectively target and eliminate HIV reservoirs.

The third highlight came from a plenary session by Dr. Ole Søgaard (Aarhus University Hospital, Denmark), a former amfAR grantee. Dr. Søgaard laid out two main cure strategies: (1) eradicating or inactivating the virus entirely and (2) training the immune system to control HIV without medication. While stem cell transplants have provided proof that eradication is possible, this method remains impractical for most people. Instead, much of the field’s focus has shifted to immune-mediated control, leveraging approaches such as therapeutic vaccines, broadly neutralizing antibodies, and repurposed drugs from cancer research. Encouragingly, some individuals have already demonstrated the ability to control HIV for years after stopping ART, proving that a functional cure is achievable.

Taken together, these studies reinforce a growing theme in HIV cure research: The immune system itself may hold the key to long-term control of the virus. Whether by enhancing CD8⁺ T cells, better characterizing the reservoir, or leveraging new therapies, we are edging closer to interventions that could allow people to live HIV-free without the need for daily medication.

As I leave CROI this year, I am more optimistic than ever that a future without HIV remains within reach. However, continued progress depends on sustained financial support for scientific studies and there is widespread anxiety in the scientific community about the future of federal funding for HIV research. Science is not a solitary endeavor; it thrives on teamwork, collaboration, and unwavering support from governments, institutions, and society at large. The fight against HIV is and has always been a collective endeavor.

Dr. Gramatica is a vice president and director of research at amfAR.

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