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Turk G, Seiger K, Lian X, et al. A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation. Ann Intern Med. 2021;doi: 10.7326/L21-0297.
Turk, G., Seiger, K., Lian, X., Sun, W., Parsons, E. M., Gao, C., Rassadkina, Y., Polo, M. L., Czernikier, A., Ghiglione, Y., Vellicce, A., Varriale, J., Lai, J., Yuki, Y., Martin, M., Rhodes, A., Lewin, S. R., Walker, B. D., Carrington, M., Siliciano, R., Siliciano, J., Lichterfeld, M., Laufer, N., & Yu, X. G. (2021). A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation. Annals of internal medicine, . https://doi.org/10.7326/L21-0297
Turk, Gabriela, et al. "A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation." Annals of internal medicine vol. (2021). doi: https://doi.org/10.7326/L21-0297
Turk G, Seiger K, Lian X, Sun W, Parsons EM, Gao C, Rassadkina Y, Polo ML, Czernikier A, Ghiglione Y, Vellicce A, Varriale J, Lai J, Yuki Y, Martin M, Rhodes A, Lewin SR, Walker BD, Carrington M, Siliciano R, Siliciano J, Lichterfeld M, Laufer N, Yu XG. A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation. Ann Intern Med. 2021 Nov 16; doi: 10.7326/L21-0297. Epub 2021 Nov 16. PMID: 34781719.
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Ann Intern Med. 2021 Nov 16; doi: 10.7326/L21-0297. Epub 2021 Nov 16.

A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation.

Annals of internal medicine

Gabriela Turk, Kyra Seiger, Xiaodong Lian, Weiwei Sun, Elizabeth M Parsons, Ce Gao, Yelizaveta Rassadkina, Maria Laura Polo, Alejandro Czernikier, Yanina Ghiglione, Alejandra Vellicce, Joseph Varriale, Jun Lai, Yuko Yuki, Maureen Martin, Ajantha Rhodes, Sharon R Lewin, Bruce D Walker, Mary Carrington, Robert Siliciano, Janet Siliciano, Mathias Lichterfeld, Natalia Laufer, Xu G Yu

Affiliations

  1. Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET - Universidad de Buenos Aires, and Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Universidad de Buenos Aires, Buenos Aires, Argentina (G.T., N.L.).
  2. Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, and Infectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts (K.S., X.L., W.S., E.M.P., C.G., M.L., X.G.Y.).
  3. Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts (Y.R., B.D.W.).
  4. Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET - Universidad de Buenos Aires, and Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina (M.L.P., A.C., Y.G.).
  5. Department of Hematology, Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina (A.V.).
  6. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (J.V., J.L., R.S., J.S.).
  7. Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (Y.Y., M.M.).
  8. The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia (A.R.).
  9. The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, and Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia (S.R.L.).
  10. Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (M.C.).

PMID: 34781719 DOI: 10.7326/L21-0297

Abstract

BACKGROUND: A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection.

OBJECTIVE: To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy.

DESIGN: Detailed investigation of virologic and immunologic characteristics.

SETTING: Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts.

PATIENT: A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication.

MEASUREMENTS: Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing.

RESULTS: No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4

LIMITATIONS: Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved.

CONCLUSION: Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection.

PRIMARY FUNDING SOURCE: National Institutes of Health and Bill & Melinda Gates Foundation.

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