Hematopoietic stem cell transplantation in the treatment of HIV infection – comparison of “Berlin patient”, “London patient” and “Dusseldorf patient”
DOI:
https://doi.org/10.15584/ejcem.2023.4.8Keywords:
AIDS, ART therapy, HIV, HSCT therapyAbstract
Introduction and aim. Human Immunodeficiency Virus-1 (HIV-1) remains one of the major issues in global public health. The standard therapy for HIV-1 positive patients includes using antiretroviral therapy (ART). These medications ensure suppression of viral replication but do not lead to a cure for the patient. The aim of this study was to present hematopoietic stem cell transplantation (HSCT) as a malignant treatment method which led to cure for three HIV-1 positive patients. Material and methods. Literature available in April 2023 was searched by using the PubMed and Google Scholar databases. Articles were selected using the following words: HIV, AIDS, HSCT therapy, ART therapy.
Analysis of the literature. In each case of these described HSCT, the donor of hematopoietic stem cells had a homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32/Δ32). This mutation leads to a permanent lack of the protein and prevents penetration of virus by using this receptor. After transplantation, all of these 3 patients remained virus-free despite discontinuation of ART therapy.
Conclusion. More research is needed to reduce the risk of using HSCT and perhaps in the future be able to use this therapy in all HIV-infected people.
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References
World Helath Organization. HIV. https://www.who.int/data/gho/data/themes/hiv-aids. Accessed April 12, 2023.
Phanuphak N, Gulick RM. HIV treatment and prevention 2019: Current standards of care. Curr Opin HIV AIDS. 2020;15(1):4-12. doi: 10.1097/COH.0000000000000588
HIV and AIDS Epidemic Global Statistics. HIV.gov. https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics/. Accessed July 6, 2023.
Wong CS, Wei L, Kim YS. HIV Late Presenters in Asia: Management and Public Health Challenges. Xu Y, ed. AIDS Res Treat. 2023;2023:1-8. doi: 10.1155/2023/9488051
Korencak M, Byrne M, Richter E, et al. Effect of HIV infection and antiretroviral therapy on immune cellular functions. JCI Insight. 2019;4(12):e126675. doi: 10.1172/JCI.INSIGHT.126675
Hütter G, Thiel E. Allogeneic transplantation of CCR5-deficient progenitor cells in a patient with HIV infection: An update after 3 years and the search for patient no. 2. AIDS. 2011;25(2):273-274. doi: 10.1097/QAD.0B013E328340FE28
Gupta RK, Peppa D, Hill AL, et al. Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report. Lancet HIV. 2020;7(5):e340-e347. doi: 10.1016/S2352-3018(20)30069-2
Reardon S. Third patient free of HIV after receiving virus-resistant cells. Nature. 2023;615(7950):13-14. doi: 10.1038/D41586-023-00479-2
Menéndez-Arias L, Delgado R. Update and latest advances in antiretroviral therapy. Trends Pharmacol Sci. 2022;43(1):16-29. doi: 10.1016/J.TIPS.2021.10.004
Gandhi RT, Bedimo R, Hoy JF, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2023;329(1):63-84. doi: 10.1001/JAMA.2022.22246
Prator CA, Donatelli J, Henrich TJ. From Berlin to London: HIV-1 Reservoir Reduction Following Stem Cell Transplantation. Curr HIV/AIDS Rep. 2020;17(4):385-393. doi: 10.1007/S11904-020-00505-2
Khalid K, Padda J, Wijeratne Fernando R, et al. Stem Cell Therapy and Its Significance in HIV Infection. Cureus. 2021;13(8):e17507. doi: 10.7759/CUREUS.17507
Surya Rao PK. CCR5 inhibitors: Emerging promising HIV therapeutic strategy. Indian J Sex Transm Dis AIDS. 2009;30(1):1-9. doi: 10.4103/0253-7184.55471
Zhen A, Kitchen S. Stem-cell-based gene therapy for HIV infection. Viruses. 2013;6(1):1-12. doi: 10.3390/V6010001
Pernet O, Yadav SS, An DS. Stem cell-based therapies for HIV/AIDS. Adv Drug Deliv Rev. 2016;103:187-201. doi: 10.1016/J.ADDR.2016.04.027
Allers K, Schneider T. CCR5Δ32 mutation and HIV infection: basis for curative HIV therapy. Curr Opin Virol. 2015;14:24-29. doi: 10.1016/J.COVIRO.2015.06.007
Rios A. HIV-related hematological malignancies: a concise review. Clin Lymphoma Myeloma Leuk. 2014;14 Suppl:96-103. doi: 10.1016/J.CLML.2014.06.020
Arslan S, Litzow MR, Cummins NW, et al. Risks and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Patients with HIV Infection. Biol Blood Marrow Transplant. 2019;25(8):e260-e267. doi: 10.1016/J.BBMT.2019.03.021
Re A, Cattaneo C, Montoto S. Treatment management of haematological malignancies in people living with HIV. Lancet Haematol. 2020;7(9):e679-e689. doi: 10.1016/S2352-3026(20)30115-0
Ambinder RF, Capoferri AA, Durand CM. Haemopoietic cell transplantation in patients living with HIV. Lancet HIV. 2020;7(9):e652-e660. doi: 10.1016/S2352-3018(20)30117-X
Kopeć-Szlęzak J. Haematopoietic stem cell in bone marrow niche. Journal of Transfusion Medicine. 2011;(3):129-135.
Lange C, Maldarelli F. Immune Reconstitution Following Allogeneic Stem Cell Transplantation in HIV infected Individuals: Years of Living Dangerously. Clin Infect Dis. 2022;74(9):1671-1674. doi: 10.1093/CID/CIAB565
Ding J, Liu Y, Lai Y. Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure. Front Immunol. 2021;12:688747. doi: 10.3389/FIMMU.2021.688747/BIBTEX
Hütter G, Nowak D, Mossner M, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009;360(7):692-698. doi: 10.1056/NEJMOA0802905
Watts G. Timothy Ray Brown. The Lancet. 2020;396(10259):1327. doi: 10.1016/s0140-6736(20)32151-6
Ding J, Liu Y, Lai Y. Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure. Front Immunol. 2021;12:1852. doi: 10.3389/FIMMU.2021.688747/BIBTEX
Gupta RK, Abdul-Jawad S, McCoy LE, et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem cell transplantation. Nature. 2019;568(7751):244. doi: 10.1038/S41586-019-1027-4
Jensen BEO, Knops E, Cords L, et al. In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation. Nat Med. 2023;29(3):583-587. doi: 10.1038/S41591-023-02213-X
Karuppusamy K V, Babu P, Thangavel S. The Strategies and Challenges of CCR5 Gene Editing in Hematopoietic Stem and Progenitor Cells for the Treatment of HIV. Stem Cell Rev Rep. 2021;17(5):1607-1618. doi: 10.1007/S12015-021-10145-7
Hsu J, Van Besien K, Glesby MJ, et al. the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1107 Team Correspondence HIV-1 remission and possible cure in a woman after haplo-cord blood transplant. Cell. 2023;186:1115-1126.e8. doi: 10.1016/j.cell.2023.02.030
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