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

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.

Development of a multiplex droplet digital PCR assay for detection of enterovirus, parechovirus, herpes simplex virus 1 and 2 simultaneously for diagnosis of viral CNS infections

“…With the advantage of absolute quantitation without a standard curve and the potential of more accurate and sensitive end-point measurements, ddPCR has been applied to pathogens detection of infectious diseases like human immunodeficiency virus (HIV) [ 17 – 19 ], hepatitis B virus (HBV) [ 20 ], hepatitis C virus (HCV) [ 21 ] and viruses in aqueous humor [ 13 ].…”

ART duration and immunometabolic state determine efficacy of DC-based treatment restoring functional HIV- specific CD8+ T cells in PLWH

“…Our PLWH cohort was defined by individuals who were under ART, with undetectable plasma HIV-1 viral load (<20 mRNA copies/ml), with no co-infection with HCV, and CD4+ T cell counts higher than 400 cells/ml. In this regard, we focused on PLWH who more likely contain preserved memory CD8+ T cells able to mediate competent immune responses, as reduction of antigen exposure on treated PLWH has been described to partially restore CD8+ T cell function and reduce exhaustion, compared to non-treated PLWH (61)(62)(63). This allowed us to evaluate the capacity of our adjuvant-DC strategy to induce CD8+ T cell responses in PLWH at different times since treatment initiation.…”

Inducible HIV-1 Reservoir Quantification: Clinical Relevance, Applications and Advancements of TILDA

“…Several studies have shown that the frequency of cells that could be induced to express HIV-1 msRNA is small in most individuals treated during AHI (Fiebig stages 1-III) ( Colby et al, 2018 ; Leyre et al, 2020 ). Furthermore, some long-term suppressed patients or elite HIV-1 controllers have significantly lower latent viral reservoirs ( Siliciano et al, 2003 ; Autran et al, 2011 ; Bertoldi et al, 2020 ; Galvez et al, 2020 ). In these cases, reservoir estimation using TILDA is technically challenging.…”