Can We Realize a Functional Cure of HIV?
##plugins.themes.bootstrap3.article.main##
##plugins.themes.bootstrap3.article.sidebar##
Abstract
Despite significant advances in antiretroviral therapy (ART), which have transformed HIV from a fatal disease into a manageable chronic condition, a definitive cure remains elusive. Functional cure, defined as durable viral remission without ongoing therapy, represents a realistic yet ambitious goal that could drastically reduce global morbidity, mortality, and transmission. Achieving this requires addressing the complex challenges posed by viral reservoirs, immune evasion, and viral latency. Recent advances in gene editing, immunotherapy, and latency-reversing agents offer promising avenues, yet each approach faces scientific, logistical, and ethical hurdles. This article argues that while a sterilizing cure—complete eradication of the virus—is currently impractical, a functional cure may be attainable through coordinated strategies that combine ART, immune modulation, and innovative biomedical interventions. By critically examining current research and emerging technologies, we can envision a future in which HIV is controlled without daily therapy, reshaping both clinical practice and global public health strategies.
##plugins.themes.bootstrap3.article.details##
HIV, Functional Cure, Antiretroviral Therapy, Viral Reservoirs, Immunotherapy
No funding source declared.
Barouch, D. H., Whitney, J. B., Moldt, B., et al. (2013). Therapeutic efficacy of potent neutralizing HIV-1–specific monoclonal antibo-dies in SHIV-infected rhesus monkeys. Nature, 503(7475), 224–228. DOI: https://doi.org/10.1038/nature12744
Caskey, M., Klein, F., Lorenzi, J. C. C., et al. (2015). Viraemia su-ppressed in HIV-1–infected humans by broadly neutralizing antibody 3BNC117. Nature, 522(7557), 487–491. DOI: https://doi.org/10.1038/nature14411
Chun, T. W., Moir, S., & Fauci, A. S. (2015). HIV reservoirs as obstacles and opportunities for an HIV cure. Nature Immunology, 16(6), 584–589. DOI: https://doi.org/10.1038/ni.3152
Cillo, A. R., Mellors, J. W. (2016). Which therapeutic strategy will achieve a cure for HIV-1? Current Opinion in Virology, 18, 14–19. DOI: https://doi.org/10.1016/j.coviro.2016.02.003
Deeks, S. G., Lewin, S. R., & Havlir, D. V. (2013). The end of AIDS: HIV infection as a chronic disease. The Lancet, 382(9903), 1525–1533. DOI: https://doi.org/10.1016/S0140-6736(13)61809-7
Eisinger, R. W., Dieffenbach, C. W., & Fauci, A. S. (2019). HIV viral load and transmissibility of HIV infection: Undetectable equals untransmitta-ble. JAMA, 321(5), 451–452.DOI: https://doi.org/10.1001/jama.2018.21167
Finzi, D., Blankson, J., Siliciano, J. D., et al. (1999). Latent infection of CD4+ T cells provides a mecha-nism for lifelong persistence of HIV-1. Nature Medicine, 5, 512–517. DOI: https://doi.org/10.1038/8394
Gupta, R. K., Abdul-Jawad, S., McCoy, L. E., et al. (2019). HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell trans-plantation. Nature, 568(7751), 244–248. DOI: https://doi.org/10.1038/s41586-019-1027-4
Hütter, G., Nowak, D., Mossner, M., et al. (2009/long-term follow-up relevance). Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. New England Journal of Medicine, 360(7), 692–698. DOI: https://doi.org/10.1056/NEJMoa0802905
Lewin, S. R., Attoye, T., Bansbach, C., Doehle, B., Dubé, K., Dybul, M., SenGupta, D., Jiang, A., Johnston, R., Lamplough, R., McCune, J. M., Nabel, G. J., Ndung'u, T., Pottage, J., Ripin, D., Rooney, J. F., Si-kazwe, I., Nsubuga, M., Warren, M., Deeks, S. G., … Sunnylands 2019 Working Group (2021). Mul-ti-stakeholder consensus on a target product profile for an HIV cure. The lancet. HIV, 8(1), e42–e50. DOI: https://doi.org/10.1016/S2352-3018(20)30234-4
Liu, B., Zou, F., Lu, L., Chen, C., He, D., Zhang, X., Tang, X., Liu, C., Li, L., & Zhang, H. (2016). Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Recei-ving Suppressive Combined Anti-retroviral Therapy. Journal of viro-logy, 90(21), 9712–9724. DOI: https://doi.org/10.1128/JVI.00852-16
Margolis, D. M., Garcia, J. V., Hazuda, D. J., & Haynes, B. F. (2016). Latency reversal and viral clearance to cure HIV-1. Science, 353(6297), aaf6517. DOI: https://doi.org/10.1126/science.aaf6517
Pitman, M. C., Lau, J. S. Y., McMahon, J. H., & Lewin, S. R. (2018). Barriers and strategies to achieve a cure for HIV. The Lancet HIV, 5(6), e317–e328. DOI: https://doi.org/10.1016/S2352-3018(18)30039-0
Saayman, S. M., Lazar, D. C., Scott, T. A., et al. (2015). Potent and targeted activation of latent HIV-1 using the CRISPR/dCas9 activator complex. Molecular The-rapy, 24(3), 488–498. DOI: https://doi.org/10.1038/mt.2015.202
Siliciano, J. D., & Siliciano, R. F. (2014). Recent developments in the search for a cure for HIV-1 infection: targeting the latent reservoir for HIV-1. The Journal of Allergy and Clinical Immunology, 134(1), 12–19. DOI: https://doi.org/10.1016/j.jaci.2014.05.026
Tucker, J. D., Rennie, S., & Su-garman, J. (2018). Social and ethical implications of HIV cure research. Journal of the Internati-onal AIDS Society, 21(1), e25072. DOI: https://doi.org/10.1002/jia2.25072
UNAIDS. (2023). Global AIDS update 2023: The path that ends AIDS. https://www.unaids.org
Xu, L., Yang, H., Gao, Y., et al. (2019). CRISPR/Cas9-mediated CCR5 ablation in human hemato-poietic stem/progenitor cells con-fers HIV-1 resistance in vivo. Mo-lecular Therapy, 27(11), 1785–1796. DOI: https://doi.org/10.1016/j.ymthe.2019.08.004.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.