• Gabriela Turk, Kyra Seiger, Xiaodong Lian, Weiwei Sun, Elizabeth M Parsons, Ce Gao, Yelizaveta Rassadkina, Maria Laura Polo, Alejandro Czernikier, Yanina Ghiglione, Alejandra Vellicce, Joseph Varriale, Jun Lai, Yuko Yuki, Maureen Martin, Ajantha Rhodes, Sharon R Lewin, Bruce D Walker, Mary Carrington, Robert Siliciano, Janet Siliciano, Mathias Lichterfeld, Natalia Laufer, and Xu G Yu.
• Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET - Universidad de Buenos Aires, and Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Universidad de Buenos Aires, Buenos Aires, Argentina (G.T., N.L.).
• Ann. Intern. Med. 2022 Jan 1; 175 (1): 9510095-100.

BackgroundA 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.ObjectiveTo 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.DesignDetailed investigation of virologic and immunologic characteristics.SettingTertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts.PatientA patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication.MeasurementsAnalysis 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.ResultsNo 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.LimitationsAbsence 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.ConclusionGenome-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 SourceNational Institutes of Health and Bill & Melinda Gates Foundation.

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