Learning About “Known Unknowns” and “Unknown Unknowns” to Cure HIV
Authors: Richard D'Aquila
Journal: Annals of Internal Medicine (2018)

Editorials20 November 2018Learning About “Known Unknowns” and “Unknown Unknowns” to Cure HIVRichard D'Aquila, MDRichard D'Aquila, MDFeinberg School of Medicine, Northwestern University, Chicago, Illinois (R.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-2822 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Medical scientists dealing with my case are not really certain what actually cured me of HIV. I think it was the lack of CCR5 protein in the donor stem cells, but…I realize I could be wrong.—Timothy Ray Brown (1)An allogeneic hematopoietic stem cell transplant (allo-HSCT) cured Timothy Ray Brown of HIV and cancer (1, 2). As he implied in the quote above, the mechanism responsible for his cure is a “known unknown.” The leading hypothesis is that immune reconstitution with cells from a donor with a mutated, nonfunctional CCR5 coreceptor for HIV played a major role. Curing HIV was ...References1. Brown TR. Timothy Ray Brown's continuing activism toward curing HIV. AIDS Res Hum Retroviruses. 2018;34:9-11. [PMID: 29256641] doi:10.1089/AID.2017.0318 CrossrefMedlineGoogle Scholar2. Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009;360:692-8. [PMID: 19213682] doi:10.1056/NEJMoa0802905 CrossrefMedlineGoogle Scholar3. Henrich TJ, Hu Z, Li JZ, Sciaranghella G, Busch MP, Keating SM, et al. Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation. J Infect Dis. 2013;207:1694-702. [PMID: 23460751] doi:10.1093/infdis/jit086 CrossrefMedlineGoogle Scholar4. Henrich TJ, Hanhauser E, Marty FM, Sirignano MN, Keating S, Lee TH, et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann Intern Med. 2014;161:319-27. [PMID: 25047577]. doi:10.7326/M14-1027 LinkGoogle Scholar5. Salgado M, Kwon M, Gálvez C, Badiola J, Nijhuis M, Bandera A, et al. Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogeneic stem cell transplant. Ann Intern Med. 2018;169:674-83. doi:10.7326/M18-0759 LinkGoogle Scholar6. Metcalf Pate KA, Pohlmeyer CW, Walker-Sperling VE, Foote JB, Najarro KM, Cryer CG, et al. A murine viral outgrowth assay to detect residual HIV type 1 in patients with undetectable viral loads. J Infect Dis. 2015;212:1387-96. [PMID: 25883388] doi:10.1093/infdis/jiv230 CrossrefMedlineGoogle Scholar7. Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018;561:479-84. [PMID: 30258136] doi:10.1038/s41586-018-0531-2 CrossrefMedlineGoogle Scholar8. Namazi G, Fajnzylber JM, Aga E, Bosch R, Acosta EP, Sharaf R, et al. The Control of HIV after Antiretroviral Medication Pause (CHAMP) study: post-treatment controllers identified from 14 clinical studies. J Infect Dis. 2018. [PMID: 30085241] doi:10.1093/infdis/jiy479 CrossrefMedlineGoogle Scholar9. Colby DJ, Trautmann L, Pinyakorn S, Leyre L, Pagliuzza A, Kroon E, et al; RV411 study group. Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection. Nat Med. 2018;24:923-6. [PMID: 29892063] doi:10.1038/s41591-018-0026-6 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.D.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-2822.Corresponding Author: Richard D'Aquila, MD, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, 625 North Michigan Avenue, Room 14-005, Chicago, IL 60611; e-mail, richard.[email protected]edu.This article was published at Annals.org on 16 October 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMechanisms That Contribute to a Profound Reduction of the HIV-1 Reservoir After Allogeneic Stem Cell Transplant Maria Salgado , Mi Kwon , Cristina Gálvez , Jon Badiola , Monique Nijhuis , Alessandra Bandera , Pascual Balsalobre , Pilar Miralles , Ismael Buño , Carolina Martinez-Laperche , Cristina Vilaplana , Manuel Jurado , Bonaventura Clotet , Annemarie Wensing , Javier Martinez-Picado , Jose Luis Diez-Martin , and Metrics 20 November 2018Volume 169, Issue 10Page: 719-720KeywordsAntiretroviral therapyBlood cellsCancer treatmentCellsDisclosureHIVImmune responseStem cellsT cellsViremia ePublished: 16 October 2018 Issue Published: 20 November 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...