VIH, POR UNA ÉTICA DE LA CURACIÓN: UN ANÁLISIS DE LOS ASPECTOS BIÓTICOS DE LA INVESTIGACIÓN ACTUAL CON VIH Y CRISPR-CAS9
DOI:
https://doi.org/10.56238/arev7n9-061Palabras clave:
Bioética, Revisión Integrativa, Acceso a la Salud, CRISPR-Cas9Resumen
La búsqueda de una cura para la infección por VIH continúa. Si bien los métodos convencionales no erradican el virus, permiten a las personas con VIH tener una mejor calidad de vida, siempre que sigan correctamente su tratamiento farmacológico. Con el avance de la biotecnología y la ingeniería genética, especialmente mediante la técnica CRISPR-Cas9, se han explorado nuevas posibilidades terapéuticas. Este estudio realizó una revisión integrativa y un análisis bioético de la investigación actual dirigida a una cura funcional del VIH mediante la manipulación genética del genoma humano. Utilizando la base de datos PubMed, se identificaron 115.538 artículos con el descriptor "VIH"; al incluir "CRISPR" se obtuvieron 444 resultados, y al añadir "cura", 83, de los cuales 80 se analizaron tras exclusiones por irrelevancia temática. La investigación destacó el desarrollo de métodos de control del VIH y las violaciones bioéticas asociadas, como la falta de representación, las fallas en el consentimiento informado y el acceso desigual a los tratamientos. La conclusión es que, a pesar del potencial de la tecnología CRISPR-Cas9, persisten importantes preocupaciones éticas. La bioética intervencionista, basada en los principios de prudencia, protección, precaución y prevención, debe guiar esta investigación. El acceso equitativo y la participación de la industria farmacéutica son esenciales para garantizar avances éticos e inclusivos, fomentando un diálogo continuo entre la ciencia y la bioética.
Descargas
Referencias
AGBOSU, E. et al. Targeted nanocarrier delivery of RNA therapeutics to control HIV infection. Pharmaceutics, [S.l.], v. 14, n. 7, p. 1352, 2022. DOI: 10.3390/pharmaceutics14071352.
AHLENSTIEL, C. L. et al. Block and lock HIV cure strategies to control the latent reservoir. Frontiers in Cellular and Infection Microbiology, [S.l.], v. 10, p. 424, 2020. DOI: 10.3389/fcimb.2020.00424.
AKKINA, R. New generation humanized mice for virus research: comparative aspects and future prospects. Virology, [S.l.], v. 479-480, p. 46-53, 2016. DOI: 10.1016/j.virol.2015.12.006.
ALBANESE, M. et al. Rapid, efficient and activation-neutral gene editing of polyclonal primary human resting CD4+ T cells allows complex functional analyses. Nature Methods, [S.l.], v. 19, n. 1, p. 81-89, 2022. DOI: 10.1038/s41592-021-01328-8.
ALLEN, A. et al. Gene editing of HIV-1 co-receptors to prevent and/or cure virus infection. Frontiers in Microbiology, [S.l.], v. 9, p. 2940, 2018. DOI: 10.3389/fmicb.2018.02940.
ANANWORANICH, J.; ROBB, M. L. The transient HIV remission in the Mississippi baby: why is this good news? Journal of the International AIDS Society, [S.l.], v. 17, 2014. DOI: 10.7448/IAS.17.1.19859.
ANLIKER, B. et al. Regulatory considerations for clinical trial applications with CRISPR-based medicinal products. The CRISPR Journal, [S.l.], v. 5, n. 3, p. 364-376, 2022. DOI: 10.1089/crispr.2022.0012.
ARTESI, M. et al. PCIP-seq: simultaneous sequencing of integrated viral genomes and their insertion sites with long reads. Genome Biology, [S.l.], v. 22, n. 1, p. 97, 2021. DOI: 10.1186/s13059-021-02307-0.
ATKINS, A. J. et al. HIV-1 cure strategies: why CRISPR? Expert Opinion on Biological Therapy, [S.l.], v. 21, n. 6, p. 781-793, 2021. DOI: 10.1080/14712598.2021.1865302.
BAKER, B. K. The TRIPS Agreement, access to HIV/AIDS pharmaceuticals, and the roles of the World Trade Organization, UNAIDS and WHO. AIDS and Intellectual Property Law, [S.l.], 2008.
BARDIN, L. Análise de conteúdo. Lisboa: Edições 70, 1977.
BAROUCH, D. H. et al. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature, [S.l.], v. 482, p. 89-93, 2012. DOI: 10.1038/nature10766.
BBC NEWS. China condena a três anos de cárcel ao polêmico cientista que realizou a primeira modificação genética de bebês. 2019. Disponível em: https://www.bbc.com/mundo/noticias-50948086. Acesso em: 4 set. 2025.
BEAUCHAMP, T. L.; CHILDRESS, J. F. Princípios de ética biomédica. São Paulo: Loyola, 2002.
BENATAR, S. R. Global health ethics: the rationale for mutual caring. International Affairs, [S.l.], v. 79, n. 1, p. 107-138, 2003. DOI: 10.1111/1468-2346.00298.
BUSMAN-SAHAY, K. et al. Eliminating HIV reservoirs for a cure: the issue is in the tissue. Current Opinion in HIV and AIDS, [S.l.], v. 16, n. 4, p. 200-208, 2021. DOI: 10.1097/COH.0000000000000688.
CARVALHO, P. et al. Fatores associados à adesão à terapia antirretroviral em adultos: revisão integrativa de literatura. Ciência & Saúde Coletiva, Rio de Janeiro, v. 24, n. 7, p. 2543-2555, 2019. DOI: 10.1590/1413-81232018247.25332017.
CHAO, T.-C. et al. The long noncoding RNA HEAL regulates HIV-1 replication through epigenetic regulation of the HIV-1 promoter. mBio, [S.l.], v. 10, n. 5, e02016-19, 2019. DOI: 10.1128/mBio.02016-19.
CHARLESWORTH, C. T. et al. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nature Medicine, [S.l.], v. 25, n. 2, p. 249-254, 2019. DOI: 10.1038/s41591-018-0326-x.
CHNEEGANS, S.; LEWIS, J.; STRAZA, T. (Eds.). Relatório de ciências da UNESCO: a corrida contra o tempo por um desenvolvimento mais inteligente - resumo executivo. Paris: UNESCO Publishing, 2021.
CHOMONT, N. Silence, escape and survival drive the persistence of HIV. Nature, [S.l.], v. 614, n. 7947, p. 236-237, 2023. DOI: 10.1038/d41586-023-00247-8.
CHRISTENSEN, K. D. et al. Assessing the costs and cost-effectiveness of genomic sequencing. Journal of Personalized Medicine, [S.l.], v. 5, n. 4, p. 470-486, 2015. DOI: 10.3390/jpm5040470.
CHUN, T.-W. et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature, [S.l.], v. 387, n. 6629, p. 183-188, 1997. DOI: 10.1038/387183a0.
CHUNG, C. H. et al. Safe CRISPR-Cas9 inhibition of HIV-1 with high specificity and broad-spectrum activity by targeting LTR NF-κB binding sites. Molecular Therapy - Nucleic Acids, [S.l.], v. 21, p. 965-982, 2020. DOI: 10.1016/j.omtn.2020.07.033.
CHUPRADIT, K. et al. Validation of promoters and codon optimization on CRISPR/Cas9-engineered jurkat cells stably expressing αRep4E3 for interfering with HIV-1 replication. International Journal of Molecular Sciences, [S.l.], v. 23, n. 23, p. 15049, 2022. DOI: 10.3390/ijms232315049.
COHEN, M. S. et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine, [S.l.], v. 365, p. 493-505, 2011. DOI: 10.1056/NEJMoa1105243.
CONG, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science, [S.l.], v. 339, p. 819-823, 2013. DOI: 10.1126/science.1231143.
COSTA, R. B.; LIMA, E. F. Ética e segurança na edição genética: implicações da tecnologia CRISPR-Cas9. Revista de Bioética e Direito, [S.l.], n. 46, p. 77-98, 2024. DOI: [inserir DOI, se disponível].
DA COSTA, L. C. et al. Repression of HIV-1 reactivation mediated by CRISPR/dCas9-KRAB in lymphoid and myeloid cell models. Retrovirology, [S.l.], v. 19, n. 1, p. 12, 2022. DOI: 10.1186/s12977-022-00597-4.
DAI, W. et al. Genome-wide CRISPR screens identify combinations of candidate latency reversing agents for targeting the latent HIV-1 reservoir. Science Translational Medicine, [S.l.], v. 14, n. 667, eabh3351, 2022. DOI: 10.1126/scitranslmed.abh3351.
DAMPIER, W. et al. HIV excision utilizing CRISPR/Cas9 technology: attacking the proviral quasispecies in reservoirs to achieve a cure. MOJ Immunology, [S.l.], v. 1, n. 4, p. 00022, 2014. DOI: 10.15406/moji.2014.01.00022.
DARCI, G. et al. The impact of HIV-1 genetic diversity on CRISPR-Cas9 antiviral activity and viral escape. Viruses, [S.l.], v. 11, n. 3, p. 255, 2019. DOI: 10.3390/v11030255.
DASH, P. K. et al. CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice. Proceedings of the National Academy of Sciences, [S.l.], v. 120, n. 19, e2217887120, 2023. DOI: 10.1073/pnas.2217887120.
DASH, P. K. et al. Sequential LASER ART and CRISPR treatments eliminate HIV-1 in a subset of infected humanized mice. Nature Communications, [S.l.], v. 10, 2753, 2019. DOI: 10.1038/s41467-019-10366-y.
DOUDNA, J. A.; CHARPENTIER, E. The new frontier of genome engineering with CRISPR-Cas9. Science, [S.l.], v. 346, n. 6213, 2014. DOI: 10.1126/science.1258096.
DRACHLER, M. L. et al. The scale of self-efficacy expectations of adherence to antiretroviral treatment: a tool for identifying risk for non-adherence to treatment for HIV. PLoS ONE, [S.l.], v. 11, n. 2, e0147443, 2016. DOI: 10.1371/journal.pone.0147443.
DRAKE, M. J.; BATES, P. Application of gene-editing technologies to HIV-1. Current Opinion in HIV and AIDS, [S.l.], v. 10, n. 2, p. 123-127, 2015. DOI: 10.1097/COH.0000000000000134.
DUBÉ, K. et al. Ethical and practical considerations for cell and gene therapy toward an HIV cure: findings from a qualitative in-depth interview study in the United States. BMC Medical Ethics, [S.l.], v. 23, n. 39, 2022. DOI: 10.1186/s12910-022-00780-8.
EPSTEIN, S. Impure science: AIDS, activism, and the politics of knowledge. Berkeley: University of California Press, 1996.
FALCINELLI, S. D. et al. Combined noncanonical NF-κB agonism and targeted BET bromodomain inhibition reverse HIV latency ex vivo. Journal of Clinical Investigation, [S.l.], v. 132, n. 8, e157281, 2022. DOI: 10.1172/JCI157281.
FAN, M.; BERKHOUT, B.; HERRERA-CARRILLO, E. A combinatorial CRISPR-Cas12a attack on HIV DNA. Molecular Therapy - Methods & Clinical Development, [S.l.], v. 25, p. 43-51, 2022. DOI: 10.1016/j.omtm.2022.02.006.
FISCHER, M. L.; ROSANELI, C. F.; LUMMERTZ, T. B.; SGANZERLA, A. Brumadinho: o que eu tenho a ver com isso?: a bioética ambiental como instrumento de cidadania. InterEspaço: Revista de Geografia e Interdisciplinaridade, [S.l.], p. e202221, 2022. DOI: 10.18766/2446-6549/interespaco.v8n1p1-19.
FLEXNER, C. et al. HIV drug development: the next 25 years. Nature Reviews Drug Discovery, [S.l.], v. 17, p. 705-726, 2007. DOI: 10.1038/nrd2336.
GARRAFA, V. Da bioética de princípios a uma bioética interventiva. Revista Bioética, [S.l.], v. 13, n. 1, p. 125-134, 2005.
GUPTA, P. K.; SAXENA, A. HIV/AIDS: current updates on the disease, treatment and prevention. Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, [S.l.], v. 91, n. 3, p. 495-510, 2021. DOI: 10.1007/s40011-021-01237-7.
GUPTA, R. M.; MUSUNURU, K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. Journal of Clinical Investigation, [S.l.], v. 124, n. 10, p. 4154-4161, 2014. DOI: 10.1172/JCI72992.
HENDERSON, L. J. et al. Advances toward curing HIV-1 infection in tissue reservoirs. Journal of Virology, [S.l.], v. 94, n. 3, e00375-19, 2020. DOI: 10.1128/JVI.00375-19.
HENDRIKS, S. et al. Reasons for being in favour of or against genome modification: a survey of the Dutch general public. Human Reproduction Open, [S.l.], v. 3, n. 1, p. 1-12, 2018. DOI: 10.1093/hropen/hoy008.
HENRICH, T. J. et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Annals of Internal Medicine, [S.l.], v. 161, p. 319-327, 2014. DOI: 10.7326/M14-1027.
HERRERA-CARRILLO, E.; GAO, Z.; BERKHOUT, B. CRISPR therapy towards an HIV cure. Briefings in Functional Genomics, [S.l.], v. 19, n. 3, p. 201-208, 2020. DOI: 10.1093/bfgp/elz039.
HERSKOVITZ, J. et al. CRISPR-Cas9 mediated exonic disruption for HIV-1 elimination. EBioMedicine, [S.l.], v. 73, 103678, 2021. DOI: 10.1016/j.ebiom.2021.103678.
HOEN, E. 't; BERGER, J.; CALMY, A.; MOON, S. Driving a decade of change: HIV/AIDS, patents and access to medicines for all. Journal of the International AIDS Society, [S.l.], v. 14, n. 1, p. 15, 2011. DOI: 10.1186/1758-2652-14-15.
HORVATH, P.; BARRANGOU, R. CRISPR/Cas, the immune system of bacteria and archaea. Science, [S.l.], v. 327, n. 5962, p. 167-170, 2010. DOI: 10.1126/science.1179555.
HOU, P. Editing of CXCR4 by CRISPR/Cas9 confers cells resistant to HIV-1 infection. Scientific Reports, [S.l.], v. 5, 15577, 2015. DOI: 10.1038/srep15577.
HUANG, Z.; NAIR, M. A CRISPR/Cas9 guidance RNA screen platform for HIV provirus disruption and HIV/AIDS gene therapy in astrocytes. Scientific Reports, [S.l.], v. 7, 5955, 2017. DOI: 10.1038/s41598-017-06269-x.
HULTQUIST, J. F. et al. A Cas9 ribonucleoprotein platform for functional genetic studies of HIV-host interactions in primary human T cells. Cell Reports, [S.l.], v. 17, n. 5, p. 1438-1452, 2016. DOI: 10.1016/j.celrep.2016.09.087.
HUSSEIN, M. et al. A CRISPR-Cas cure for HIV/AIDS. International Journal of Molecular Sciences, [S.l.], v. 24, n. 2, p. 1563, 2023. DOI: 10.3390/ijms24021563.
HUTTER, G. et al. Long-term control of HIV by CCR5 Δ32/Δ32 stem-cell transplantation. New England Journal of Medicine, [S.l.], v. 360, n. 7, p. 692-698, 2009. DOI: 10.1056/NEJMoa0802905.
IHRY, R. J. et al. p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells. Nature Medicine, [S.l.], v. 24, n. 7, p. 939-946, 2018. DOI: 10.1038/s41591-018-0050-6.
IMRAN, M. et al. Modern biotechnology-based therapeutic approaches against HIV infection. Biomedical Reports, [S.l.], v. 7, n. 6, p. 504-507, 2017. DOI: 10.3892/br.2017.1006.
INNOVATIVE GENOMICS INSTITUTE. Paying for CRISPR cures: the economics of genetic therapies. 2022. Disponível em: https://innovativegenomics.org/news/paying-for-crispr-cures/. Acesso em: 4 set. 2025.
JANSSENS, J. et al. CRISPR/Cas9-induced mutagenesis corroborates the role of Transportin-SR2 in HIV-1 nuclear import. Microbiology Spectrum, [S.l.], v. 9, n. 2, e01336-21, 2021. DOI: 10.1128/Spectrum.01336-21.
JEROME, K. R. Disruption or excision of provirus as an approach to HIV cure. AIDS Patient Care and STDs, [S.l.], v. 30, n. 12, p. 551-555, 2016. DOI: 10.1089/apc.2016.0172.
JIANKUI, H. et al. Draft ethical principles for therapeutic assisted reproductive technologies. The CRISPR Journal, [S.l.], v. 1, n. 6, p. 4-6, 2018. DOI: 10.1089/crispr.2018.0051.
JINEK, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science, [S.l.], v. 337, n. 6096, p. 816-821, 2012. DOI: 10.1126/science.1225829.
JONAS, H. O princípio responsabilidade: ensaio de uma ética para a tecnologia civilizacional. Tradução de Marijane Lisboa e Luiz Barros Montez. Rio de Janeiro: Contraponto; Ed. PUC-Rio, 2006.
JOUNG, J. K.; SANDER, J. D. TALENs: a widely applicable technology for targeted genome editing. Nature Reviews Molecular Cell Biology, [S.l.], v. 14, n. 1, p. 49-55, 2013. DOI: 10.1038/nrm3486.
KALIDASAN, V.; THEVA, D. K. Lessons learned from failures and success stories of HIV breakthroughs: are we getting closer to an HIV cure? Frontiers in Microbiology, [S.l.], v. 11, p. 46, 2020. DOI: 10.3389/fmicb.2020.00046.
KANDULA, U. R.; WAKE, A. D. Promising stem cell therapy in the management of HIV and AIDS: a narrative review. Biologics, [S.l.], v. 16, p. 89-105, 2022. DOI: 10.2147/BTT.S349131.
KHALILI, K. et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & Cell, [S.l.], v. 6, n. 5, p. 363-372, 2015a. DOI: 10.1007/s13238-015-0153-5.
KHALILI, K. et al. Genome editing strategies: potential tools for eradicating HIV-1/AIDS. Journal of Neurovirology, [S.l.], v. 21, n. 3, p. 310-321, 2015b. DOI: 10.1007/s13365-015-0341-y.
KHALILI, K.; WHITE, M. K.; JACOBSON, J. M. Novel AIDS therapies based on gene editing. Cellular and Molecular Life Sciences, [S.l.], v. 74, n. 13, p. 2439-2450, 2017. DOI: 10.1007/s00018-017-2479-5.
KLATZMANN, D. et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature, [S.l.], v. 312, p. 767-768, 1984. DOI: 10.1038/312767a0.
KLITZMAN, R.; BAYER, R. Mortal secrets: truth and lies in the age of AIDS. Baltimore: Johns Hopkins University Press, 2003.
KORDELAS, L.; VERHEYEN, J.; ESSER, S. Shift of HIV tropism in stem-cell transplantation with CCR5 Delta32 mutation. New England Journal of Medicine, [S.l.], v. 371, p. 880-882, 2014. DOI: 10.1056/NEJMc1405805.
LEBBINK, R. J. et al. Combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape. Scientific Reports, [S.l.], v. 7, 41968, 2017. DOI: 10.1038/srep41968.
LIMA, K. L.; MORAES, L. M. Transparência e responsabilidade no desenvolvimento de medicamentos: o caso do HIV. Políticas Públicas em Saúde, [S.l.], v. 14, n. 4, p. 610-629, 2023.
LIU, Z. et al. Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection. Cell & Bioscience, [S.l.], v. 7, p. 47, 2017. DOI: 10.1186/s13578-017-0174-5.
LUNDGREN, J. D. et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. New England Journal of Medicine, [S.l.], v. 373, n. 9, p. 795-807, 2015. DOI: 10.1056/NEJMoa1506816.
MAGRO, G.; CALISTRI, A.; PAROLIN, C. Targeting and understanding HIV latency: the CRISPR system against the provirus. Pathogens, [S.l.], v. 10, n. 10, p. 1257, 2021. DOI: 10.3390/pathogens10101257.
MAINA, E. K. et al. A review of current strategies towards the elimination of latent HIV-1 and subsequent HIV-1 cure. Current HIV Research, [S.l.], v. 19, n. 1, p. 14-26, 2021. DOI: 10.2174/1570162X18666200810104524.
MARTINS, C. D.; FERREIRA, D. E. Comparação da eficiência no desenvolvimento de fármacos entre empresas de biotecnologia e instituições públicas. Journal of Health Economics, [S.l.], v. 22, n. 4, p. 567-586, 2022.
MEHMETOGLU-GURBUZ, T. et al. Combination gene therapy for HIV using a conditional suicidal gene with CCR5 knockout. Virology Journal, [S.l.], v. 18, n. 1, p. 31, 2021. DOI: 10.1186/s12985-021-01500-3.
METZL, J. F. Hackeando Darwin: engenharia genética e o futuro da humanidade. Tradução de Renato Cardozo. São Paulo: Faro Editorial, 2020.
MEYER-RATH, G.; OVER, M. HIV treatment as prevention: modelling the cost of antiretroviral treatment—state of the art and future directions. PLoS Medicine, [S.l.], v. 9, n. 7, e1001247, 2012. DOI: 10.1371/journal.pmed.1001247.
MINISTÉRIO DA SAÚDE (BRASIL). Conselho Nacional de Saúde. Resolução nº 466, de 12 de dezembro de 2012. Dispõe sobre diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Diário Oficial da União, Brasília, 13 jun. 2013.
MORANGUINHO, I.; VALENTE, S. T. Block-and-lock: new horizons for a cure for HIV-1. Viruses, [S.l.], v. 12, n. 12, p. 1443, 2020. DOI: 10.3390/v12121443.
MUSUNURU, K. The CRISPR generation: the story of the world’s first gene-edited babies. New Jersey: BookBaby, 2019.
NERYS-JUNIOR, A. et al. Comparison of the editing patterns and editing efficiencies of TALEN and CRISPR-Cas9 when targeting the human CCR5 gene. Genetics and Molecular Biology, [S.l.], v. 41, n. 1, p. 167-179, 2018. DOI: 10.1590/1678-4685-GMB-2017-0065.
NGUYEN, K. et al. Multiple histone lysine methyltransferases are required for the establishment and maintenance of HIV-1 latency. mBio, [S.l.], v. 8, n. 1, e00133-17, 2017. DOI: 10.1128/mBio.00133-17.
NOHAMA, N. et al. CRISPR e edição genômica: técnica, bioética e controvérsias. Ponta Grossa: Atena, 2023.
OPHINNI, Y. et al. Multiplexed tat-targeting CRISPR-Cas9 protects T cells from acute HIV-1 infection with inhibition of viral escape. Viruses, [S.l.], v. 12, n. 11, p. 1223, 2020. DOI: 10.3390/v12111223.
ORGANIZAÇÃO PARA COOPERAÇÃO ECONÔMICA E DESENVOLVIMENTO (OCDE). Key biotechnology indicators. Paris, 2012. Disponível em: https://www.oecd.org/sti/inno/keybiotechnologyindicators.htm. Acesso em: 4 set. 2025.
PACKARD, T. A. et al. CCL2: a chemokine potentially promoting early seeding of the latent HIV reservoir. mBio, [S.l.], v. 13, n. 5, e01891-22, 2022. DOI: 10.1128/mbio.01891-22.
PATEL, S. et al. T-cell therapies for HIV: preclinical successes and current clinical strategies. Cytotherapy, [S.l.], v. 18, n. 8, p. 931-942, 2016. DOI: 10.1016/j.jcyt.2016.04.007.
PEDERSEN, S. F. et al. Inhibition of a chromatin and transcription modulator, SLTM, increases HIV-1 reactivation identified by a CRISPR inhibition screen. Journal of Virology, [S.l.], v. 96, n. 13, e00577-22, 2022. DOI: 10.1128/jvi.00577-22.
PERNET, O.; YADAV, S. S. Stem cell-based therapies for HIV/AIDS. Advanced Drug Delivery Reviews, [S.l.], v. 103, p. 187-201, 2016. DOI: 10.1016/j.addr.2016.04.027.
PETER, L.; WOLFE, S. M. Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries. New England Journal of Medicine, [S.l.], v. 337, n. 12, p. 853-856, 1997. DOI: 10.1056/NEJM199709183371212.
PETERSON, T. A.; MACLEAN, A. G. Current and future therapeutic strategies for lentiviral eradication from macrophage reservoirs. Journal of Neuroimmune Pharmacology, [S.l.], v. 14, n. 1, p. 68-93, 2019. DOI: 10.1007/s11481-018-9814-4.
PHAM, H. T.; MESPLÈDE, T. The latest evidence for possible HIV-1 curative strategies. Drugs in Context, [S.l.], v. 7, 212522, 2018. DOI: 10.7573/dic.212522.
PLUTA, A.; JAWORSKI, J.; CORTÉS-RUBIO, C. Balance between retroviral latency and transcription: based on HIV model. Pathogens, [S.l.], v. 10, n. 1, p. 16, 2020. DOI: 10.3390/pathogens10010016.
POTTER, V. R. Bioethics: bridge to the future. Englewood Cliffs: Prentice-Hall, 1971.
QU, D. et al. The variances of Sp1 and NF-κB elements correlate with the greater capacity of Chinese HIV-1 B’-LTR for driving gene expression. Scientific Reports, [S.l.], v. 6, 34532, 2016. DOI: 10.1038/srep34532.
RACITI, C. G. et al. Ethical considerations for research involving pregnant women living with HIV and their young children: a systematic review of the empiric literature and discussion. BMC Medical Ethics, [S.l.], v. 22, n. 1, p. 38, 2021. DOI: 10.1186/s12910-021-00601-2.
RATHORE, A. et al. CRISPR-based gene knockout screens reveal deubiquitinases involved in HIV latency in two Jurkat cell models. Scientific Reports, [S.l.], v. 10, n. 1, p. 5350, 2020. DOI: 10.1038/s41598-020-62335-9.
REUST, C. Common adverse effects of antiretroviral therapy for HIV disease. American Family Physician, [S.l.], v. 83, n. 12, p. 1443-1451, 2011.
ROSANELI, C. F. et al. O legado ético no enfrentamento da pandemia COVID-19: a sinergia entre a perspectiva global e a identidade regional. HOLOS, [S.l.], v. 4, p. 1-19, 2021. DOI: 10.15628/holos.2021.11146.
ROYCHOUDHURY, P. et al. Viral diversity is an obligate consideration in CRISPR/Cas9 designs for targeting the HIV reservoir. BMC Biology, [S.l.], v. 16, n. 1, p. 75, 2018. DOI: 10.1186/s12915-018-0544-1.
RUTISHAUSER, R. L. et al. TCF-1 regulates HIV-specific CD8+ T cell expansion capacity. JCI Insight, [S.l.], v. 6, n. 3, e136648, 2021. DOI: 10.1172/jci.insight.136648.
RYDER, S. P. CRISPRbabies: notes on a scandal. The CRISPR Journal, [S.l.], v. 1, n. 1, p. 355-357, 2018. DOI: 10.1089/crispr.2018.29010.spr.
SAAYMAN, S. M. et al. Potent and targeted activation of latent HIV-1 using the CRISPR/dCas9 activator complex. Molecular Therapy, [S.l.], v. 24, n. 3, p. 488-489, 2016. DOI: 10.1038/mt.2016.12.
SCHELLER, S. H. et al. Biallelic, selectable, knock-in targeting of CCR5 via CRISPR-Cas9 mediated homology directed repair inhibits HIV-1 replication. Frontiers in Immunology, [S.l.], v. 13, 821190, 2022. DOI: 10.3389/fimmu.2022.821190.
SAMJI, H. et al. Closing the gap: increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS ONE, [S.l.], v. 8, n. 12, e81355, 2013. DOI: 10.1371/journal.pone.0081355.
SANTOS, G. H.; ALMEIDA, H. I. Conflitos de interesse em pesquisas financiadas por empresas de biotecnologia: desafios éticos e soluções. Ética em Pesquisa, [S.l.], v. 10, n. 3, p. 300-318, 2023.
SCHRAMM, F. R. Bioética da proteção: ferramenta válida para enfrentar problemas morais na era da globalização. Revista Bioética, [S.l.], v. 16, n. 1, p. 11-23, 2008.
SILVA, A. M.; ROCHA, B. L. Impacto do financiamento privado na inovação biotecnológica: um estudo de caso da pesquisa sobre o HIV. Revista Brasileira de Inovação em Saúde, [S.l.], v. 15, n. 2, p. 234-250, 2023.
SLAYMAKER, I. M. et al. Rationally engineered Cas9 nucleases with improved specificity. Science, [S.l.], v. 351, n. 6268, p. 84-88, 2016. DOI: 10.1126/science.aad5227.
SMITH, L. et al. Silencing integrated SIV proviral DNA with TAR-specific CRISPR tools. Journal of Medical Primatology, [S.l.], v. 49, n. 5, p. 269-279, 2020. DOI: 10.1111/jmp.12480.
SMITH, L. M. et al. Multiplexed simian immunodeficiency virus-specific paired RNA-guided Cas9 nickases inactivate proviral DNA. Journal of Virology, [S.l.], v. 95, n. 23, e00882-21, 2021. DOI: 10.1128/JVI.00882-21.
SOROKINA, A. et al. Detection of CCR5Δ32 mutant alleles in heterogeneous cell mixtures using droplet digital PCR. Frontiers in Molecular Biosciences, [S.l.], v. 9, 805931, 2022. DOI: 10.3389/fmolb.2022.805931.
SULLIVAN, N. et al. Designing safer CRISPR/Cas9 therapeutics for HIV: defining factors that regulate and technologies used to detect off-target editing. Frontiers in Microbiology, [S.l.], v. 11, p. 1872, 2020. DOI: 10.3389/fmicb.2020.01872.
SULLIVAN, N. T. et al. Novel gRNA design pipeline to develop broad-spectrum CRISPR/Cas9 gRNAs for safe targeting of the HIV-1 quasispecies in patients. Scientific Reports, [S.l.], v. 9, n. 1, p. 17088, 2019. DOI: 10.1038/s41598-019-52353-9.
'T HOEN, E. F. The global politics of pharmaceutical monopoly power: drug patents, access, innovation and the application of the WTO Doha Declaration on TRIPS and public health. Netherlands: AMB Publishers, 2009.
URNOV, F. D. et al. Genome editing with engineered zinc finger nucleases. Nature Reviews Genetics, [S.l.], v. 11, n. 9, p. 636-646, 2010. DOI: 10.1038/nrg2842.
WANG, G. et al. A combinatorial CRISPR-Cas9 attack on HIV-1 DNA extinguishes all infectious provirus in infected T cell cultures. Cell Reports, [S.l.], v. 17, n. 11, p. 2819-2826, 2016. DOI: 10.1016/j.celrep.2016.11.057.
WEATHERLEY, D. A. V.; BOSWELL, M. T.; ROWLAND-JONES, S. L. Targeting TRIM5α in HIV cure strategies for the CRISPR-Cas9 era. Frontiers in Immunology, [S.l.], v. 8, p. 1616, 2017. DOI: 10.3389/fimmu.2017.01616.
WOLLEBO, H. S. et al. CRISPR/Cas9 system as an agent for eliminating polyomavirus JC infection. PLoS ONE, [S.l.], v. 10, n. 9, e0136046, 2015. DOI: 10.1371/journal.pone.0136046.
XIAO, Q.; GUO, D.; CHEN, S. Application of CRISPR/Cas9-based gene editing in HIV-1/AIDS therapy. Frontiers in Cellular and Infection Microbiology, [S.l.], v. 9, p. 69, 2019. DOI: 10.3389/fcimb.2019.00069.
XU, L. et al. CRISPR/Cas9-mediated CCR5 ablation in human hematopoietic stem/progenitor cells confers HIV-1 resistance in vivo. Molecular Therapy, [S.l.], v. 25, n. 8, p. 1782-1789, 2017. DOI: 10.1016/j.ymthe.2017.04.027.
YANG, X. et al. PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-κB signaling. EMBO Reports, [S.l.], v. 21, n. 11, e49305, 2020. DOI: 10.15252/embr.201949305.
YANG, X. et al. MAT2A-mediated S-adenosylmethionine level in CD4+ T cells regulates HIV-1 latent infection. Frontiers in Immunology, [S.l.], v. 12, p. 745784, 2021. DOI: 10.3389/fimmu.2021.745784.
YE, L. et al. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection. Proceedings of the National Academy of Sciences, [S.l.], v. 111, n. 26, p. 9591-9596, 2014. DOI: 10.1073/pnas.1407473111.
YEH, Y.-H. J. et al. The clonal expansion dynamics of the HIV-1 reservoir: mechanisms of integration site-dependent proliferation and HIV-1 persistence. Viruses, [S.l.], v. 13, n. 9, p. 1858, 2021. DOI: 10.3390/v13091858.
YIN, C. et al. Functional screening of guide RNAs targeting the regulatory and structural HIV-1 viral genome for a cure of AIDS. AIDS, [S.l.], v. 30, n. 8, p. 1163-1174, 2016. DOI: 10.1097/QAD.0000000000001077.
YIN, C. et al. In vivo excision of HIV-1 provirus by saCas9 and multiplex single-guide RNAs in animal models. Molecular Therapy, [S.l.], v. 25, n. 5, p. 1168-1186, 2017. DOI: 10.1016/j.ymthe.2017.03.017.
YODER, K. E. A CRISPR/Cas9 library to map the HIV-1 provirus genetic fitness. Acta Virologica, [S.l.], v. 63, n. 2, p. 129-138, 2019. DOI: 10.4149/av_2019_202.
YU, S. et al. Experimental treatment of SIV-infected macaques via autograft of CCR5-disrupted hematopoietic stem and progenitor cells. Molecular Therapy - Methods & Clinical Development, [S.l.], v. 17, p. 520-531, 2020. DOI: 10.1016/j.omtm.2020.02.001.
ZHANG, Q. et al. Genome-wide CRISPR/Cas9 transcriptional activation screen identifies a histone acetyltransferase inhibitor complex as a regulator of HIV-1 integration. Nucleic Acids Research, [S.l.], v. 50, n. 12, p. 6687-6701, 2022. DOI: 10.1093/nar/gkac476.
ZHANG, Y. et al. CRISPR/gRNA-directed synergistic activation mediator (SAM) induces specific, persistent and robust reactivation of the HIV-1 latent reservoirs. Scientific Reports, [S.l.], v. 5, 16277, 2015. DOI: 10.1038/srep16277.
ZHU, W. et al. The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology, [S.l.], v. 12, n. 1, p. 22, 2015. DOI: 10.1186/s12977-015-0150-2.
