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. 

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.

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.  

The Quest for an HIV Cure Looms Large

By: Sarah Hooper, intern, ADAP Advocacy Association, and senior at East Carolina University

Earlier this year, it was revealed by the National Institutes of Health (NIH) that it would pump $14.6 million into a HIV research program headed up by the University of Southern California (USC) and the Fred Hutchinson Cancer Research Center. The aim of the research program is to eliminate the need for HIV patients to take daily medication, and to hopefully achieve an overall cure. 

Photo Source: RT News App

According to End Points News, the therapy would allow a patient’s own stem cells to fight the HIV infection and allow them to make new immune cells when the infection is fought. (End Point News)

“The approach was inspired by three patients who appear to have been cured of the virus — all of whom received blood stem cell transplants from donors who carried a mutation in the CCR5 gene. One of them, dubbed the “Berlin patient,” had been off antiretroviral drugs from 2007,” End Point News said.

In 2006, Timothy Ray Brown (also known as the Berlin patient) was diagnosed with myeloid leukemia. In 2007, Brown received two bone marrow transplants, and halted his HIV medications in the process (ScienceMag). Since the bone marrow transplant, researchers have only found traces of HIV, none of which is able to replicate in Brown’s system- effectively curing him of HIV.

NIH’s new research program is using similar technology in its search to find a cure for HIV. By using stem cells to fight the disease, the need for medication is much lesser, as one’s own body can fight HIV. However, the process Brown went through to fully cure himself of HIV is intense.

“The first is the process of conditioning, in which doctors destroyed Brown’s own immune system with chemotherapy and whole-body irradiation to prepare him for his bone marrow transplant. His oncologist, Gero Hütter, who was then with the Free University of Berlin, also took an extra step that he thought might not only cure the leukemia but also help rid Brown’s body of HIV. He found a bone marrow donor who had a rare mutation in a gene that cripples a key receptor on white blood cells the virus uses to establish an infection. The third possibility is his new immune system attacked remnants of his old one that held HIV-infected cells, a process known as graft versus host disease,” ScienceMag said. 

In September 2020, Brown passed away from his cancer, and the HIV community mourned his loss.

Photo Source: HIV Plus Magazine

The search for a cure to HIV has been ongoing since the virus was discovered. Treatment with antiretrovirals has been a massive step away from a death sentence and towards a normal life for HIV patients. The issue with the HIV virus is it can be hidden in cells while being suppressed by current HIV treatment. The only HIV patients who have been successfully cured of the virus were also undergoing intense treatments for a separate cancer diagnosis, according to ViiV Healthcare. 

These patients underwent a bone marrow transplant in which an HIV free bone marrow was placed in their body, which is a high-risk surgery as is. 

“While their treatments were extremely high risk and not amenable to wide scale implementation, these instances of cure bring hope of what is possible in our efforts to end the HIV epidemic,” ViiV Healthcare said. 

The NIH initiative to eliminate the need for daily medication is an incredible effort made available by years of previous research and effective treatment. If successful, this effort could change the lives of millions of HIV patients in the United States and around the world. 

References:

• A cure for HIV the end goal. (n.d.). Retrieved September 17, 2020, from https://viivhealthcare.com/en-gb/our-stories/innovation-hiv-science/towards-a-cure-exploring-cure-and-remission-in-hiv/
• DeFeudis, N. (2020, September 03). Researchers teamed up to develop a 'three in one' HIV treatment - and the NIH is throwing in $14.6M. Retrieved September 16, 2020, from https://endpts.com/researchers-teamed-up-to-develop-a-three-in-one-hiv-treatment-and-the-nih-is-throwing-in-14-6m/
• Jon Cohen Sep. 25, 2., Meredith Wadman Sep. 16, 2., Adrian Cho Sep. 15, 2., Ian Morse Sep. 14, 2., Eli Cahan Sep. 14, 2., Scott Waldman, E., . . . Rebekah Tuchscherer Aug. 26, 2. (2017, December 10). How did the 'Berlin patient' rid himself of HIV? Retrieved September 16, 2020, from https://www.sciencemag.org/news/2014/09/how-did-berlin-patient-rid-himself-hiv

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.