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

TURK, GABRIELA; SEIGER, KYRA; LIAN, XIAODONG; SUN, WEIWEI; PARSONS, ELIZABETH M.; GAO, CE; RASSADKINA, YELIZAVETA; POLO, MARIA LAURA; CZERNIKIER, ALEJANDRO; GHIGLIONE, YANINA; VELLICCE, ALEJANDRA; VARRIALE, JOSEPH; LAI, JUN; YUKI, YUKO; MARTIN, MAUREEN; RHODES, AJANTHA; LEWIN, SHARON R.; WALKER, BRUCE D.; CARRINGTON, MARY; SILICIANO, ROBERT; SILICIANO, JANET; LICHTERFELD, MATHIAS; LAUFER, NATALIA; YU, XU G.

ANN. INTERN. MED.

American College of Physicians

Año: 2022 vol. 175 p. 95 - 100

0003-4819

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.