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HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml -1 , >10,000 copies ml -1 for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8 + T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in cellular immunity were directly correlated to pre-treatment 3BNC117-sensitivity. Notably, increased HIV-1-specific immunity is associated with partial or complete ART-free virologic control during treatment interruption for up to 4 years. Our findings suggest that bNAb treatment at the time of ART initiation maintains HIV-1-specific CD8 + T cell responses that are associated with ART-free virologic control., (© 2022. The Author(s).)

A growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phase-separated molecular 'sponges', stabilized by quinary (transient and weak) interactions, control proteins involved in numerous biological functions. Retroviruses such as HIV-1 form by self-assembly when their genomic RNA (gRNA) traps Gag and GagPol polyprotein precursors. Infectivity requires extracellular budding of the particle followed by maturation, an ordered processing of ∼2400 Gag and ∼120 GagPol by the viral protease (PR). This leads to a condensed gRNA-NCp7 nucleocapsid and a CAp24-self-assembled capsid surrounding the RNP. The choreography by which all of these components dynamically interact during virus maturation is one of the missing milestones to fully depict the HIV life cycle. Here, we describe how HIV-1 has evolved a dynamic RNP granule with successive weak-strong-moderate quinary NC-gRNA networks during the sequential processing of the GagNC domain. We also reveal two palindromic RNA-binding triads on NC, KxxFxxQ and QxxFxxK, that provide quinary NC-gRNA interactions. Consequently, the nucleocapsid complex appears properly aggregated for capsid reassembly and reverse transcription, mandatory processes for viral infectivity. We show that PR is sequestered within this RNP and drives its maturation/condensation within minutes, this process being most effective at the end of budding. We anticipate such findings will stimulate further investigations of quinary interactions and emergent mechanisms in crowded environments throughout the wide and growing array of RNP granules.

Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in human immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV patients at different stages of HIV disease progression. In this cross-sectional study, CE from ApoB-depleted plasma, lipids levels, viral load (VL), CD4+/CD8+ T-cells, high-sensitive C-reactive protein (hsCRP), and lipoprotein (a) were evaluated in untreated HIV-infected patients (UHIVs; n = 43), elite controllers (ECs; n = 8), HIV-exposed seronegative individuals (HESNs; n = 32), and healthy controls (HCs; n = 14). Among UHIVs, those with CD4+ <500 cells/mm 3 presented the lowest significant CE, HDL cholesterol (HDL-C), and ApoAI levels. ECs showed similar HDL-C, ApoAI, and CE compared with HCs. Among UHIVs, CE positively correlated with CD4+ T-cell counts (Beta: 1.05; 95% CI: 1.02; 1.07), and for VL higher than 3.8 log, CE was inversely associated with VL (Beta: 0.70; 95% CI: 0.51; 0.95). Remarkably, HESNs presented higher CE (0.78 ± 0.14) than UHIVs (0.65 ± 0.17; P = 0.0005), but lower than HCs (0.90 ± 0.13; P = 0.009). hsCRP levels were highest in the UHIV group (0.45 ± 0.49). CE was sensitive to HIV disease progression. Low CE in HIV patients was associated with lower CD4+ T-cells and higher VL and hsCRP. CE was also lower in HESNs compared with HCs. Our results suggest that immune status secondary to HIV progression and exposure influence plasma HDL-CE capacity., (Copyright © 2018 Tort et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers., Results: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200 cp/ml) and 5 uninfected individuals (HIV-) through TaqMan Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs became significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-&#95;block 1), VP and ART individuals clustered together in a second block (VP/ART&#95;block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-&#95;block and down-expressed in VP/ART&#95;block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays., Conclusions: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.