Casado, ConcepcionGalvez, CristinaPernas, MariaTarancon-Diez, LauraRodriguez, CarmenSanchez-Merino, VíctorVera, MarOlivares, IsabelDe Pablo-Bernal, RebecaMerino-Mansilla, AlbertoDel Romero, JorgeLorenzo-Redondo, RamonRuiz-Mateos, EzequielSalgado, MaríaMartinez-Picado, JavierLopez-Galindez, Cecilio2022-11-032022-11-032020-02-05Casado C, Galvez C, Pernas M, Tarancon-Diez L, Rodriguez C, Sanchez-Merino V, et al. Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure. Sci Rep. 2020 Feb 5;10(1):1902http://hdl.handle.net/10668/4324Elite 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Disease progressionHIV-1Spontaneous cureDNAViral loadElite controllers, HIVVirusesProgresión de la enfermedadVIH-1ADNVirusCarga viralVIH no-progresivosMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease ProgressionMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV InfectionsMedical Subject Headings::Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression::Remission, SpontaneousMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Microbiological Techniques::Viral LoadMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Microbiological Processes::Virus Physiological Processes::Virus ReplicationMedical Subject Headings::Persons::Persons::Patients::Survivors::HIV Long-Term SurvivorsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, BiologicalMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-LymphocytesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Microbial::Genes, Viral::Genes, envMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::ImmunityMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNAresearch article32024974open access10.1038/s41598-020-58696-y2045-2322PMC7002478