A possible sterilizing cure of HIV-1 infection without stem cell transplantation
Annals of internal medicine, 2022•acpjournals.org
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 …
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 …
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+ 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.
Primary Funding Source
National Institutes of Health and Bill & Melinda Gates Foundation.
acpjournals.org