Marty VandenBroek, MSc Candidate, Translational Medicine
The current challenges and strategies for treating HIV was the topic of discussion at this past week’s Medical Grand Rounds, The Quest for the Holy Grail, presented by Dr. Santiago Perez. Dr. Perez shared the progress made in his studies and those of his peers, as well as his personal expertise from years studying the disease in Mexico, France, and Canada. He followed his presentation with a roundtable discussion with the TMED class to delve further into his experience and what the future holds for HIV treatment.
The current treatment for HIV is antiretroviral therapy (ART), a combination of drugs that are effective at controlling the replication and progression of the virus to manage the disease. This therapy allows patients to live effectively normal lives but is not a true cure. Dr. Perez stressed the importance of finding that cure, despite the effectiveness of ART. He shared discussions with patients who are desperate to be ‘freed’ of the disease. Despite the disease being under control, they still face the stigma of HIV, and even in some countries persecution and imprisonment should they transmit the virus. This leads to a fear of the disease, propagated by societies and media that are uninformed of how well the virus can be managed. Dr. Perez even shared a genuine story highlighting how the most harm to patients is due not to the disease itself, but the social stigma surrounding it.
Two patients have been cured of HIV using haematopoietic stem cell transplantation (HSCT), a therapy that replaces a patient’s immune cells with those from a donor. Both cases involved stem cells with a mutation in CCR5, a receptor that is key to the viral life cycle. However, the mutant CCR5 may not be the key to the cure. Surprisingly, Dr. Perez showed that patients who developed graft versus host disease (GVHD) as a result of HSCT may be cured of HIV, regardless of whether CCR5 was mutated or not. We discussed with Dr. Perez the potential ethical concerns of using GVHD to cure HIV and weighing the risk of inducing GVHD versus other alternatives. The true curative ability of HSCT with GVHD is not yet known, as while these patients appear to be HIV free, they remain on ART as a precaution, as the withdrawal of treatment poses its own risks and ethical concerns.
Other therapies have been trialled in animal models of HIV including gene therapy, which comes with its own ethical concerns should it be applied to humans. In addition, immunotherapies like anti-α4β7 treatment have had varying success, as one study appear to cure every animal, but when the same study was repeated last year not a single animal was cured.
Dr. Perez believed most in the use of CAR T-cell therapy, which allows a patient’s own T cells to be reprogrammed to fight the disease and should minimize the risks to patients. However, further research is required to make this treatment option more effective before being used in humans. This avenue is currently being explored and may only be years away from being applicable to HIV in the clinic.
Regardless of which treatment strategy emerges to cure HIV, Dr. Perez believes with the resources available today, it is possible to end the HIV/AIDS epidemic. By following the 90/90/90 rule, that is that 90% of people with HIV know their status, and 90% of those people receive full ART therapy, and 90% of those individuals have viral suppression, we can change the lives of millions of people worldwide. It requires everyone to be tested for HIV and making policy changes to ensure everyone has accessible ART, both at home and abroad.
At the end of our discussion, Dr. Perez shared his experience travelling the world as part of his research career. He encouraged everyone to explore different cultures, to open your mind and become a better person and researcher. He also shared one skill he thinks everyone should learn for self improvement: cooking. It allows you to take care of yourself, which is of utmost importance, but also teaches you to follow procedures to produce a desired result. Learning to be a good cook means you can adapt and improvise when needed, within limits; you may be able to replace butter with margarine in some cases, but milk and cream are not the same!
It was a pleasure to have Dr. Perez present at grand rounds, and on behalf of the TMED program, thank you for sharing your passion and insights!