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

• Autores: Turk, Gabriela Julia Ana; Seiger, Kyra; Lian, Xiaodong; Sun, Weiwei; Parsons, Elizabeth M.; Gao, Ce; Rassadkina, Yelizaveta; Polo, Maria Laura; Czernikier, Alejandro; Ghiglione, Yanina Alexandra; Vellicce, Alejandra Fabiana; 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 Lorna; Yu, Xu G.
• Año de publicación: 2022
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: HIV; CURE; VIRAL RESERVOIRS; ELITE CONTROLLER
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Seiger, Kyra. Massachusetts Institute of Technology; Estados Unidos
Fil: Lian, Xiaodong. Massachusetts Institute of Technology; Estados Unidos
Fil: Sun, Weiwei. Massachusetts Institute of Technology; Estados Unidos
Fil: Parsons, Elizabeth M.. Massachusetts Institute of Technology; Estados Unidos
Fil: Gao, Ce. Massachusetts Institute of Technology; Estados Unidos
Fil: Rassadkina, Yelizaveta. Massachusetts Institute of Technology; Estados Unidos
Fil: Polo, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Czernikier, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Vellicce, Alejandra Fabiana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Varriale, Joseph. No especifíca;
Fil: Lai, Jun. No especifíca;
Fil: Yuki, Yuko. No especifíca;
Fil: Martin, Maureen. No especifíca;
Fil: Rhodes, Ajantha. University of Melbourne; Australia
Fil: Lewin, Sharon R.. University of Melbourne; Australia. Monash University; Australia
Fil: Walker, Bruce D.. Massachusetts Institute of Technology; Estados Unidos
Fil: Carrington, Mary. Massachusetts Institute of Technology; Estados Unidos
Fil: Siliciano, Robert. No especifíca;
Fil: Siliciano, Janet. No especifíca;
Fil: Lichterfeld, Mathias. Massachusetts Institute of Technology; Estados Unidos
Fil: Laufer, Natalia Lorna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina
Fil: Yu, Xu G.. Massachusetts Institute of Technology; Estados Unidos