Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study
| Autor: | Kevin Einkauf, Joseph D. Yao, Dylan Hampton, Mathias Lichterfeld, Stephen W. Wietgrefe, Timothy W. Schacker, Patrick G. Dean, Tzong-Hae Lee, Sekar Natesampillai, Stacey A. Rizza, Stephane Hua, Rémi Fromentin, Jason V. Baker, Xu G. Yu, John D. Zeuli, Douglas D. Richman, Nicolas Chomont, Frank S. Rhame, Ashley T. Haase, Michael P. Busch, Steven M. Lada, Tae Wook Chun, Andrew D. Badley, Nathan W. Cummins, Mark R. Litzow, Guinevere Q. Lee, Sheila M. Keating |
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| Přispěvatelé: | Lewin, Sharon R |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RNA viruses Male Cell Transplantation lcsh:Medicine HIV Infections Pathology and Laboratory Medicine Biochemistry Medical and Health Sciences White Blood Cells 0302 clinical medicine Immunodeficiency Viruses Stem Cell Research - Nonembryonic - Human Animal Cells Medicine and Health Sciences Blood and Lymphatic System Procedures Leukocytes 030212 general & internal medicine Phylogeny T Cells virus diseases General Medicine Hematology Viral Load Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma 3. Good health Nucleic acids Infectious Diseases Anti-Retroviral Agents Medical Microbiology Viral Pathogens Lentivirus Viruses HIV/AIDS Stem cell Pathogens Cellular Types Infection Viral load Research Article Immune Cells Immunology Mononuclear Surgical and Invasive Medical Procedures Cytotoxic T cells Biology DNA replication Peripheral blood mononuclear cell Microbiology Virus 03 medical and health sciences Clinical Research Virology General & Internal Medicine Retroviruses Genetics Humans T Helper Cells Microbial Pathogens Transplantation Blood Cells lcsh:R Organisms Biology and Life Sciences HIV Leukapheresis Cell Biology DNA biology.organism_classification Stem Cell Research Viral Replication 030104 developmental biology Good Health and Well Being Viral replication Leukocytes Mononuclear HIV-1 Stem Cell Transplantation |
| Zdroj: | PLoS medicine, vol 14, iss 11 PLoS Medicine, Vol 14, Iss 11, p e1002461 (2017) PLoS Medicine Cummins, Nathan W; Rizza, Stacey; Litzow, Mark R; Hua, Stephane; Lee, Guinevere Q; Einkauf, Kevin; et al.(2017). Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.. PLoS medicine, 14(11), e1002461. doi: 10.1371/journal.pmed.1002461. UC Office of the President: Research Grants Program Office (RGPO). Retrieved from: http://www.escholarship.org/uc/item/6mz8z03f |
| Popis: | Background Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. Methods and findings We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures—including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue—the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. Conclusions allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs. Andrew Badley and colleagues study the viral reservoir in an individual with HIV infection after allogeneic stem cell transplantation. Author summary Why was this study done? Currently there is no cure for HIV infection. The only previously documented case of HIV cure occurred in the setting of stem cell transplantation for acute myeloid leukemia. However, other similar cases have not resulted in HIV cure. This observational study was done to further describe in detail the effects of allogeneic stem cell transplantation on residual HIV in a patient being treated for acute lymphoblastic leukemia. What did the researchers do and find? We prospectively collected blood and tissue samples from before and after stem cell transplantation and measured the HIV reservoir size using multiple complementary techniques. We found that the size of the HIV reservoir decreased substantially after transplantation to levels at or below the limit of detection of most assays. We observed a prolonged remission from HIV rebound after antiretroviral treatment interruption in the post-transplant period. The genetic sequence of the rebounding virus in the blood clustered closely with sequences from blood prior to treatment interruption. What do these findings mean? These findings affirm that allogeneic stem cell transplantation can profoundly decrease the size of the HIV reservoir. However, current technologies for measuring reservoir size in blood are insufficiently sensitive to predict HIV cure. Until new biomarkers of HIV cure are developed, the decision to discontinue antiretroviral therapy after allogeneic stem cell transplantation to assess a possible cure should be undertaken cautiously. |
| Databáze: | OpenAIRE |
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