TY - JOUR
T1 - A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation
AU - Turk, Gabriela
AU - Seiger, Kyra
AU - Lian, Xiaodong
AU - Sun, Weiwei
AU - Parsons, Elizabeth M.
AU - Gao, Ce
AU - Rassadkina, Yelizaveta
AU - Polo, Maria Laura
AU - Czernikier, Alejandro
AU - Ghiglione, Yanina
AU - Vellicce, Alejandra
AU - Varriale, Joseph
AU - Lai, Jun
AU - Yuki, Yuko
AU - Martin, Maureen
AU - Rhodes, Ajantha
AU - Lewin, Sharon R.
AU - Walker, Bruce D.
AU - Carrington, Mary
AU - Siliciano, Robert
AU - Siliciano, Janet
AU - Lichterfeld, Mathias
AU - Laufer, Natalia
AU - Yu, Xu G.
N1 - Publisher Copyright:
© 2021 American College of Physicians.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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 CCR5D32 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+ T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. 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.
AB - 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 CCR5D32 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+ T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. 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.
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U2 - 10.7326/L21-0297
DO - 10.7326/L21-0297
M3 - Article
C2 - 34781719
AN - SCOPUS:85124979090
SN - 0003-4819
VL - 175
SP - 95
EP - 100
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 1
ER -