The theme of this year’s International AIDS Conference was “Resilience,” which seemed especially fitting given the ongoing challenges of COVID-19 and convening the conference online.
The “London patient”
It was also epitomized in the experience of Adam Castillejo, the “London patient,” who shared the story of his HIV diagnosis, cancer treatment, and ultimate cure of both by stem cell transplantation. Mr. Castillejo described his journey from skepticism to hope as he recounted the grueling challenges of undergoing a stem cell transplant and the rigors of participating as a research subject. But his main message to everyone living with HIV and in this time of COVID-19 was, “Don’t be afraid. Don’t despair. Don’t give up hope.”
Indeed, the cure-focused pre-conference included notes of hope in the summaries of recent research advances provided by Drs. Lillian Cohn and Katherine Bar. Among the top 10 advances were two stemming from the amfAR Institute for HIV Cure Research. First, the discovery of a marker in the blood that can predict that virus is about to re-emerge after antiretroviral therapy (ART) has been stopped. And second, the design of a new type of CAR T cell that kills HIV reservoir cells.
amfAR-supported research featured prominently in the top clinical advances too, including the development at the amfAR Institute of whole-body PET imagining of the reservoir, and the ability to conduct the complex ROADMAP study that tested a shock-and-kill approach using romidepsin plus antibodies.
Understanding the reservoir
Dr. Nicolas ChomontAccurately measuring the reservoir, and changes occurring naturally or as a result of interventions, was widely discussed at the conference. In particular, a new assay called IPDA (Intact Proviral DNA Assay) developed in the lab of Dr. Robert Siliciano appears to give a more accurate picture of reservoir size than previous, more labor-intensive tests. It has revealed that intact proviruses, the ones most likely to cause viral rebound when ART is stopped, appear to decay faster than defective proviruses. Dr. Michael Peluso from the amfAR Institute used the assay to differentiate those who naturally control their HIV infection from those who don’t. And, as described by Dr. Doug Nixon, amfAR grantee Dr. Brad Jones has optimized the IPDA assay so that it can be used to assess the reservoir in a wider range of HIV subtypes.
In an approach that gets at the nature of the reservoir, amfAR grantee Dr. Nicolas Chomont provided one explanation for expansions and contractions of the reservoir over time. Each infected CD4 T cell is specialized to fight a specific infectious pathogen, such as influenza, cytomegalovirus, Epstein-Barr virus, etc. When those HIV-infected CD4 T cells encounter the pathogen they are designed to fight, they expand in number, and thus the number of reservoir cells expands. Once the infection is cleared, the number of CD4 T cells contracts again, as does the size of that fraction of the reservoir.
Gene therapy and the future
Looking towards the future of cure research, another particularly interesting session, “Pushing the boundaries: new approaches to a cure,” focused largely on gene therapy approaches. amfAR grantee Dr. Joachim Hauber described a gene-editing tool developed by his team in Germany that directly excises the HIV provirus from infected cells. Others described ways to engineer cells to become factories for potent neutralizing antibodies, or to protect cells from infection.
The diversity of approaches to an HIV cure and the encouraging advances being made on many fronts were on full display at AIDS 2020. They give us every reason to sustain our momentum, keep pushing forward, and to heed Mr. Castillejo’s exhortation: Don’t give up hope.
Dr. Johnston is amfAR vice president and director of research.