Permanent control of HIV-1 pathogenesis in exceptional elite controllers : a model of spontaneous cure
Casado, Concepcion (Virología Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiología, Instituto de Salud Carlos III)
Gálvez, Cristina (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Pernas, María (Virología Molecular, Laboratorio de Referencia e Investigación en Retrovirus, Centro Nacional de Microbiología, Instituto de Salud Carlos III)
Tarancon-Diez, Laura (Universidad de Sevilla)
Rodriguez, Carmen (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Sanchez-Merino, Víctor (Centro Nacional de Microbiología, Instituto de Salud Carlos III)
Vera, Mar (Hospital Clínico San Carlos (Madrid))
Olivares, Isabel (Centro Nacional de Microbiología, Instituto de Salud Carlos III)
De Pablo-Bernal, Rebeca (Universidad de Sevilla)
Merino-Mansilla, Alberto (Centro Nacional de Microbiología, Instituto de Salud Carlos III)
Del Romero, Jorge (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Lorenzo-Redondo, Ramon (Northwestern University Feinberg School of Medicine, Chicago, USA)
Ruiz-Mateos, Ezequiel (Universidad de Sevilla)
Salgado, María (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martinez-Picado, Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Lopez-Galindez, Cecilio (Centro Nacional de Microbiología, Instituto de Salud Carlos III)

Date:	2020
Abstract:	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/10 6 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.
Grants:	Ministerio de Economía y Competitividad PI16/00684 Instituto de Salud Carlos III PI19/01127 Ministerio de Economía y Competitividad RD16/0025/0020
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 10 (february 2020) , ISSN 2045-2322

DOI: 10.1038/s41598-020-58696-y
PMID: 32024974

11 p, 2.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles