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00925njm 22002777a 4500 dc Casado, Concepcion author Gálvez, Cristina author Pernas, Maria author Tarancon-Diez, Laura author Rodriguez, Carmen author Sanchez-Merino, Victor author Vera, Mar author Olivares, Isabel author De Pablo-Bernal, Rebeca author Merino-Mansilla, Alberto author Del Romero, Jorge author Lorenzo-Redondo, Ramon author Ruiz-Mateos, Ezequiel author Salgado, María author Martinez-Picado, Javier author Lopez-Galindez, Luis Cecilio author 2020-02-05 Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/106 CD4+ T-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure. Sci Rep. 2020 Feb 5;10(1):1902. 10.1038/s41598-020-58696-y 2045-2322 2045-2322 Scientific reports 32024974 http://hdl.handle.net/20.500.12105/9112 Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure