Thursday, March 2, 2023

HIV Cure: Trial and Error Sheds New Light

By: Ranier Simons, ADAP Blog Guest Contributor

According to the World Health Organization (WHO), at the end of 2021, about 38.4 million people globally were living with HIV/AIDS.[1] Medical science has advanced through the years, creating novel treatments for many illnesses, eradicating diseases from the global population, and finding cures for others. However, a permanent cure for HIV remains elusive. Researchers have recently announced a fifth person that has been cured of HIV. While the news is exciting and further adds to knowledge about the virus, the mechanism of the cure is not scalable. Additionally, it is important to note that a promising HIV-vaccine also recently failed advanced-stage clinical trials. 

A Cure for HIV?
Photo Source: Scientific Scarsdalian

A 53-year-old man, known as the "Dusseldorf patient", is the fifth and latest person to be cured of HIV due to a blood stem cell transplant.[2] This is the exact mechanism by which four other people have been cured of HIV. This man and the others received a blood stem cell transplant as an aggressive late-stage effort to treat leukemia. 

In 2013, doctors destroyed the patient's cancerous bone marrow and subsequently healthy bone marrow as well and replaced it with donor stem cells from a person who had a mutation that rendered them resistant to HIV infection.[3] The mutation was in the genes for the CCR5 receptor, a receptor HIV needs to enter immune cells. The mutation prevents the CCR5 receptor from being expressed on the surface of immune cells. The transplanted stem cells grew and replaced the old bone marrow, giving the patient a new HIV-resistant immune system. In 2018, the Dusseldorf patient stopped taking ART and has remained HIV-virus-free.[3]

The first person to be cured of HIV/AIDS as a result of a stem-cell transplant to treat blood cancer was Timothy Ray Brown in 2007. He was known as the "Berlin patient", and his cure was confirmed in 2009. Another patient, the "London patient", was reported as being cured in 2019. A 63-year-old man known as the "City of Hope" patient and a woman known as the "New York patient" were reported in scientific literature in 2022 as being cured. The "City of Hope" patient, thus far, has been the person who has lived with HIV the longest. At one point in his HIV journey, he had an AIDS diagnosis, having had HIV since 1998.[4] 

Unfortunately, blood stem cell transplantation is not a scalable solution, and it is only used in extreme cases for people battling blood cancers with no other options. It cannot be used as a cure for all patients living with HIV because the risks are too significant. It is not guaranteed to work and is very dangerous since it requires wiping out a person's entire immune system, and that state leaves a patient open to infections with no protection. Additionally, it is possible a person's body could reject the donor stem cells as well.

Pathways to a Cure
Photo Source: POZ Magazine

January 2023 also brought news of a failed HIV-vaccine clinical trial. The Mosaico Study, a phase 3 clinical trial conducted by the HIV Vaccine Trials Network(HVTN), was ended due to the results of an interim review.[5] The Mosaico Study vaccine was what is known as a 'mosaic vaccine.' This means that it contains genetic material from a variety of HIV strains prevalent worldwide to trigger a broad immune response.[5] The study focused on cisgender men and transgender people who have sex with cisgender men and/or transgender people from around the world. The failure of the trial was reported when it was found that the vaccine was ineffective in preventing infections compared with the placebo.[6]  Over the past 40 years, clinical trials on HIV vaccines have reached phase 3 only eight times.[6] All have failed.

A significant factor in why HIV is so challenging to cure is how it operates. When HIV enters the body, some of the immune cells it infects are long-lived immune cells that soon become latent. Those sleeping cells can stay dormant for years. While those infected immune cells are dormant, they are not replicating HIV. Antiretroviral therapies target infected cells that are actively replicating new copies of HIV. Thus, the "sleeping cells" are not being targeted. The latent or "sleeping" cells are what scientists refer to as HIV reservoirs in the body. Those infected cells can wake up and become active at any time. That is why it is essential to be consistent with antiretroviral adherence. 

We may not have a cure for HIV/AIDS. However, the disappointing vaccine trials and the science learned from the extreme stem cell transplants are still valuable and push us closer to conquering the virus. Trial and error will eventually produce powerful tools to beat HIV/AIDS.

[1] World Health Organization. (2023). HIV. Retrieved from https://www.who.int/data/gho/data/themes/hiv-aids#:~:text=Globally%2C%2038.4%20million%20%5B33.9%E2%80%93,considerably%20between%20countries%20and%20regions

[2] Sathyakumar, K. (2023, February 20). 5th person confirmed to be cured of HIV. Retrieved from https://abcnews.go.com/Health/5th-person-confirmed-cured-hiv/story?id=97323361

[3] Reardon, S.(2023, February 21). Third patient free of HIV after recieving virus-resistant cells. Retrieved from https://www.nature.com/articles/d41586-023-00479-2

[4] Marquez, L.(2022, July 27). Patient achieves HIV and blood cancer remission three decades after HIV diagnosis through stem cell transplant at City of Hope. Retrieved from  https://www.cityofhope.org/patient-achieves-hiv-and-blood-cancer-remission-three-decades-after-hiv-diagnosis-through-stem-cell#:~:text=Known%20as%20the%20City%20of,is%20now%2066%20years%20old

[5] Fred Hutchinson Cancer Center. (2023, January 27). Phase 3 Mosaic-Based Investigational HIV Vaccine Study Discontinued Following Disappointing Results of Planned Data Review. Retrived from https://www.hvtn.org/news/news-releases/2023/01/phase-3-mosaic-based-investigational-hiv-vaccine-study-discontinued-following-disappointing-results-planned-data-review.html

[6] Loewy, M. (2023, February 13). Researchers Voice 'Frustration' at Failed HIV Vaccine Trial. Retrieved from https://www.medscape.com/viewarticle/988191#vp_1

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.  

No comments: