A recent case study demonstrates that a haplo-cord blood transplant can be an effective way to treat HIV-1. The published study is a case study of a woman diagnosed with Acute myeloid leukemia (a type of cancer in which bone marrow produces a large number of abnormal cells). She is a mixed-race woman who was diagnosed with HIV-1 infection four years before her acute myeloid leukemia (AML) diagnosis and was on antiretroviral treatment for her HIV-1.
HIV Virus
What are haploidentical blood transplants?
In Haplo-identical blood transplants, blood-producing cells (stem cells) from a related donor are matched with the recipient’s blood using the HLA (human leukocyte antigen) typing. After that, the blood is given to the recipient to replace diseased blood cells. A haploidentical transplant is when half of the HLA of the donor’s blood is a match to that of the recipient. The patient in this study received a haplo-cord transplant containing cord blood cells and haploidentical stem cells from a donor.
What is the CCR5 mutation?
Scientists noted that a frameshift mutation eliminates the cell surface expression of CCR5 (a receptor gene targeted by HIV-1) to infect T-cells (a type of immune cell). This frameshift mutation, a naturally occurring genetic variation in about 10 percent of the white Northern European population, makes a person resistant to HIV-1 variants that target CCR5. Before this study, only two case studies of patients who received CCR5 stem cell transplants and recovered from HIV-1. So, in this study, they aimed to find a possible donor with this type of mutation and assess the patient’s recovery after this transplant.
What did this study entail?
This study is part of the IMPAACT P1107. IMPAACT P1107 is an observational study about people living with HIV-1 who need an allogeneic stem cell transplant for their underlying illnesses. Scientists have provided details of her various blood test values indicating the course of her HIV-1 and her recovery after the transplant. To be concise, when she was diagnosed with HIV-1, her plasma viral load was higher than 1 million HIV-1 RNA copies/ml. Initially, she received ART during an acute HIV-1 infection. However, she had a latent HIV-1 reservoir at the time of transplant, measuring 1.38 infectious units/million, a level that is indicative of chronic HIV-1 infection.
The ART was revised multiple times during treatment for HIV-1. Her viral load was under control during the ART therapy, and the levels fell below the clinical limit to less than 20 HIV-1 RNA copies per ml. When she was diagnosed with AML after four years of her diagnosis of HIV-1, she also received chemotherapy that resulted in remission of AML.
The transplant and initial recovery
Researchers utilized the Stemcyte registry (a company aiming at storing and providing cord blood units) to find a CCR5 Δ32 mutated cord blood unit with an HLA match of 5 out of 8. They also found a haploidentical adult donor with the CCR5 allele. In 2017, the patient went through a haploidentical transplant followed by a cord blood unit of HLA match of ⅝. She also received prophylactic treatment against Graft versus Host disease and post-transplant infections. She was discharged 17 days after the transplant. Two weeks after her transplant, her lymphoid and myeloid blood lineages mainly contained haploidentical donor blood around 80% and 98%, respectively, and her B and T cells returned to normal levels by 6 and 13 months, respectively.
Recovery post-transplant
The patient went through periodic assessments after the transplant to assess her recovery and undergo blood tests to measure levels of HIV-1 RNA in her blood. Researchers mentioned that she suffered asymptomatic episodes of EBV, cytomegalovirus, and mild respiratory tract viruses. However, her overall recovery has been very promising.
She had undetectable levels of HIV RNA after the transplant at various intervals. She remained HIV-1-free for over 55 months in follow-up assessments. Similarly, her immune cell markers also exhibited a pattern indicative of her HIV-1 remission.
Limitations of the study
The researchers posit that it is a successful way to treat and possibly cure HIV-1 infection, considering previous evidence and evidence of this case study. However, they have mentioned that their study has limitations surrounding the complexity of the treatment method, the need for further studies, and several failed treatment cases using the same transplant method for HIV-1 treatment. They encourage further research to address these limitations and build the evidence base for this treatment.
Significance of this study
The current study provides a way forward for finding a possible cure for HIV-1 infection. Further research focused on studying a large number of patients and following them long-term may shed light on the effectiveness of this treatment. Although there is limited data on this particular type of treatment, it can stimulate further research to corroborate these findings. It can also stimulate thinking about finding additional CCR5-containing cord units.
The provided link provides further details regarding the participating institutions, funding agencies, and two other case studies studying the impact of similar treatments against HIV-1.
References
Hsu, J., Van Besien, K., Glesby, M. J., Pahwa, S., Coletti, A., Warshaw, M. G., Petz, L. D., Moore, T. B., Chen, Y. H., Pallikkuth, S., Dhummakupt, A., Cortado, R., Golner, A., Bone, F., Baldo, M., Riches, M., Mellors, J. W., Tobin, N. H., Browning, R., Persaud, D., Bryson, Y., & the IMPAACT P1107 Team. (2023). HIV-1 remission and possible cure in a woman after haplo-cord blood transplant. Cell, 186(6), 1115–1126. https://doi.org/10.1016/j.cell.2023.02.030
