Extremely low viral reservoir in treated chronically HIV-1-infected individuals
Cristina Gálvez, Víctor Urrea, Judith Dalmau, Montse Jiménez, Bonaventura Clotet, Valérie Monceaux, Nicolas Huot, Lorna Leal, Victoria González-Soler, María González‐Cao, Michaela Müller‐Trutwin, Asier Sáez‐Cirión, Felipe García, Julià Blanco, Javier Martínez‐Picado, María Salgado
Abstract
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/10 6 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/10 6 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/10 6 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 + T TM and T EMRA in the absence of cART, and higher CD8 + T N 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