The first woman cured from HIV: What is waiting in the future?

by Selina Zhao, Contributing Writer

In February, a woman* was reported as the third person ever to be cured of HIV. Unlike conventional treatments, this patient underwent a novel stem cell transplant involving umbilical cord stem cells. The patient chose not to disclose her identity, but the doctors and scientists involved in her treatment revealed that she is of diverse racial background. In the past, two male patients have already been confirmed to be cured of HIV, but what intrigued scientists about this patient is the fact that she is a female of mixed race (4).

Before discussing the patient’s uniqueness, one has to understand the peculiarity of HIV. HIV, or Human Immunodeficiency Virus, can cause Acquired Immunodeficiency syndrome (AIDS). HIV is a retrovirus targeting immune cells in the body, specifically CD4⁺ T cells. Acute HIV infection will lead to a drastic depletion of CD4⁺ T cells in the blood, disrupting the regular immune response against HIV. This depletion of immune cells and the ineffective immune response against HIV eventually lead to the acquisition of AIDS (5).

However, thanks to medical advancements, the rate of HIV infection can be controlled using antiretroviral therapy accompanied by a variety of antiretroviral medications, such as Nucleotide Reverse Transcriptase Inhibitors that impede HIV from replicating its genes. In severe cases of AIDS, stem cell transplants using bone marrow would be administered as a last resort, as they are accompanied by intense side effects (1,5). The two cured male patients both received bone marrow transplants from donors resistant to HIV infection, but they both suffered from the graft-versus-host disease — a disease caused by donor cells attacking host cells (4).

But here comes the interesting part: the female patient who  received the umbilical cord blood transplant did not develop the graft-versus-host disease and only experienced mild side effects. One of the patient’s physicians suspects that the less specific cord blood transplant was responsible (4). Unlike bone marrow transplants, cord blood transplant donors do not have to be a perfect match with the recipient because of the higher versatility of cord blood stem cells and the lower need of HLA compatibility between the donor and the recipient (6). It is important to note that the patient initially received the umbilical cord blood transplant to treat her acute myeloid leukemia. Prior to the transplant, she had already received blood stem cells from a first-degree relative to treat her leukemia, which may have propped her immune system for the umbilical cord blood transplant (4). Since cord blood cells require time to fully infuse in the host body, the blood stem cells from the relative interacted with the immune system first, potentially preparing it for a smoother cord blood cell transplant, similar to how an attenuated vaccine props the body against the actual virus (4,6). Hence, researchers believe that this combination of blood stem cells minimized the impact of the donor cells on the host cells and made the transplant less dangerous. 

Seeing the success of a third potential HIV-free patient, researchers are compelled to reevaluate the effect of HIV on different individuals based on sex and race. Due to shorter and more exposed genital tracts, women are more susceptible to HIV transmission compared to men. But at a given rate of HIV infections, women were observed to have distinctively more CD8⁺ T cell activation, despite having lower HIV viral loads during early infection (7). While CD4⁺ T cells are essential in an immune response, they recruit CD8⁺ T cells to do the actual killing of the viral infected cell (3). Hormone levels also affect the progression of HIV infection. Estrogen and its receptor in the body has been identified to directly repress the transcription of HIV genes required for HIV replication. Aside from hormones, genetic differences also contribute to different HIV progression in men and women. The X chromosome carries critical genes that code for essential transcription factors, such as FOXP3, required for regular immune responses, which likely explains why women show lower HIV viral loads during early infection due to their additional X chromosome (1,7). 

The patient’s racial identity also intrigued researchers. The homozygous genetic mutation that confers resistance to HIV infection is largely found in individuals that have ancestry from northern Europe; even so, only 1% of modern northern Europeans express the HIV-resistant genotype. Due to her diverse racial backgrounds, it was difficult to find a compatible cord blood donor. Since the HIV-resistance gene has to be homozygous to be functional, the donor must be homozygous for this gene that is found more often in those of  northern European descent. However, to prevent the recipient’s body from rejecting the donor stem cells, the donor must also be compatible with the recipient for other genes as well, implying the donor is likely mixed race as well. Thus, it was challenging to find a mixed race donor who is homozygous for the gene predominantly found in northern Europeans (4). The patient’s acceptance of the cord blood transplant also provides scientists with additional information of potential novel HIV-resistant genes. Since women and racial minorities were historically neglected in clinical trials of HIV therapy, researchers are encouraged to expand their field of research to find a potential cure for HIV/AIDS (2,7).

Although no cures or vaccines have been currently discovered to eliminate HIV, the recovery of this patient from HIV reassures researchers and physicians that HIV is curable. Fourteen months after the transplant, the patient now shows no signs of HIV in blood tests. A full recovery will be confirmed when she stays off antiviral therapy for thirty-seven months; she is currently at the twenty-month mark (4). As researchers continue to investigate umbilical cord blood transplants, a potential cure for HIV could be the next evolutionary step for medicine.

*Note: The use of the terms “men” and “women” in this article only refers to their sex assigned at birth and not their gender identities. 

Edited by Laura Reumont

References

1. An, P., & Winkler, C. A. (2010). Host genes associated with HIV/AIDS: Advances in gene discovery. Trends in Genetics, 26(3), 119–131. https://doi.org/10.1016/j.tig.2010.01.002
2. Johnston, R. E., & Heitzeg, M. M. (2015). Sex, Age, Race and Intervention Type in Clinical Studies of HIV Cure: A Systematic Review. AIDS Research and Human Retroviruses, 31(1), 85–97. https://doi.org/10.1089/aid.2014.0205 
3. Laidlaw, B. J., Craft, J. E., & Kaech, S. M. (2016). The multifaceted role of CD4+ T cells in CD8+ T cell memory. Nature Reviews Immunology, 16(2), 102–111. https://doi.org/10.1038/nri.2015.10 
4. Mastroianni, B. (2022, February 21). First Woman ‘cured’ of HIV through stem cell treatments: What we know. Healthline. Retrieved March 10, 2022, from https://www.healthline.com/health-news/first-woman-cured-of-hiv-through-stem-cell-treatments-what-we-know
5. Moir, S., Chun, T.-W., & Fauci, A. S. (2011). Pathogenic mechanisms of HIV disease. Annual Review of Pathology: Mechanisms of Disease, 6(1), 223–248. https://doi.org/10.1146/annurev-pathol-011110-130254
6. Rocha, V., Labopin, M., Sanz, G., Arcese, W., Schwerdtfeger, R., Bosi, A., Jacobsen, N., Ruutu, T., de Lima, M., Finke, J., Frassoni, F., & Gluckman, E. (2004). Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. New England Journal of Medicine, 351(22), 2276–2285. https://doi.org/10.1056/nejmoa041469 
7. Scully, E. P. (2018). Sex differences in HIV infection. Current HIV/AIDS Reports, 15(2), 136–146. https://doi.org/10.1007/s11904-018-0383-2 

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