Extremely low viral reservoir in treated chronically HIV-1-infected individuals

EBioMedicine

Valérie Monceaux¹  Lorna Leal¹  Victor Urrea¹  Maria Salgado²  Javier Martinez-Picado³  Maria González-Cao⁴  Victoria González-Soler⁵  Julià Blanco⁶  Felipe García⁷  Asier Sáez-Cirión⁸  Michaela Müller-Trutwin⁸  Nicolas Huot⁹  Cristina Gálvez⁹  Montse Jimenez⁹  Judith Dalmau⁹  Bonaventura Clotet⁹ 

[1] Autonomous University of Barcelona, Cerdanyola del Vallés, Spain;CIBER Epidemiologia y Salud Publica (CIBERESP), Spain;Microbiology Department. Laboratori Clínic Metropolitana Nord. University Hospital “Germans Trias i Pujol”, Badalona, Spain. Department of Genetics and Microbiology. Autonomous University of Barcelona, Spain;University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain;‘Lluita contra la SIDA’ Foundation, Badalona, Spain;Centre for Epidemiological Studies on Sexually Transmitted Diseases and HIV/AIDS of Catalonia (CEEISCAT), Health Department, Generalitat de Catalunya, Spain;Infectious Diseases Department, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain;Institut Pasteur, Unité HIV Inflammation et Persistance, Paris, France;IrsiCaixa AIDS Research Institute and Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain;

关键词: HIV reservoir;    HIV latency;    total HIV-DNA;    immunophenotyping;    HIV-specific antibodies;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Small viral reservoirs are found predominantly in HIV-1 controllers and individuals treated during acute/early HIV-1 infection. However, other HIV+ individuals could naturally also harbour low viral reservoirs. Methods: We screened 451 HIV-1-infected treated-individuals with suppressed plasma viremia for at least 3 years and stored cryopreserved peripheral blood mononuclear cells (PBMCs). Total HIV-DNA was analysed in PBMCs with ddPCR. Individuals with <50 HIV-DNA copies/106 PBMCs constitute the ‘Low Viral Reservoir Treated’ cohort (LoViReT). Longitudinal samples were obtained from 12 chronically treated LoViReT and compared to 13 controls (>50 HIV-DNA copies/106 PBMCs) to analyse total HIV-DNA, T-cell and NK-cell populations, HIV-1 specific antibodies, and plasma inflammation markers. Findings: We found that 9.3% of the individuals screened had <50 HIV-DNA copies/106 PBMCs. At least 66% initiated cART during the chronic phase of HIV-1 infection (cp-LoViReT). Cp-LoViReT harboured lower levels of HIV-DNA before cART and after treatment introduction the decays were greater compared to controls. They displayed a marked decline in quantity and avidity in HIV-specific antibodies after initiation of cART. Cp-LoViReT had fewer CD8+ TTM and TEMRA in the absence of cART, and higher CD8+ TN after 18 months on therapy. Interpretation: Treated chronically HIV-1-infected LoViReT represent a new phenotype of individuals characterized by an intrinsically reduced viral reservoir, less impaired CD8+ T-cell compartment before cART, and low circulating HIV-1 antigens despite being treated in the chronic phase of infection. The identification of this unique group of individuals is of great interest for the design of future eradication studies. Funding: MSD Spain

【 授权许可】

Unknown