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Introduction Elite controllers (ECs) represent a small subset of people living with HIV-1 (PLHIV), less than 1%, who can maintain undetectable viral load in the absence of antiretroviral therapy (ART) [...], BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS. The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next- generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS. PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs. CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART. FUNDING. Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.

INTRODUCTION: Rapidly progressive dementias (RPDs) are a group of neurological disorders characterized by a rapid cognitive decline. The diagnostic value of blood‐based biomarkers for Alzheimer's disease (AD) in RPD has not been fully explored. METHODS: We measured plasma brain‐derived tau (BD‐tau) and p‐tau181 in 11 controls, 15 AD patients, and 33 with RPD, of which 19 were Creutzfeldt‐Jakob disease (CJD). RESULTS: Plasma BD‐tau differentiated AD from RPD and controls (p = 0.002 and p = 0.03, respectively), while plasma and cerebrospinal fluid (CSF) p‐tau181 distinguished AD from RPD (p < 0.001) but not controls from RPD (p > 0.05). The correlation of CSF t‐tau with plasma BD‐tau was stronger (r = 0.78, p < 0.001) than the correlation of CSF and plasma p‐tau181 (r = 0.26, p = 0.04). The ratio BD‐tau/p‐tau181 performed equivalently to the CSF t‐tau/p‐tau181 ratio, differentiating AD from CJD (p < 0.0001). DISCUSSION: Plasma BD‐tau and p‐tau181 mimic their corresponding cerebrospinal fluid (CSF) markers. P‐tau significantly increased in AD but not in RPD. Plasma BD‐tau, like CSF t‐tau, increases according to neurodegeneration intensity. [ABSTRACT FROM AUTHOR]

Aim: Aim of this study was to evaluate the effect of anakinra (ANK) addition to remdesivir (RDV) on all-cause 28-day mortality in patients hospitalized with COVID-19. Patients & methods: ANK was administered intravenously at a dose of 5 mg/kg every 12 h in patients with severe respiratory failure and pronounced inflammatory status. 58 patients were treated with RDV + ANK, 219 patients with RDV. Results: The estimate of mortality at 28 days was 17.2% in the RDV + ANK group and 21.4% in the RDV group. Median time to death was 14 days in the RDV + ANK group and 19 in the RDV group. Conclusion: Despite severe respiratory failure and pronounced inflammatory status, patients who received RDV + ANK had similar mortality compared with patients who received RDV. In this study, we looked at hospitalized patients with COVID-19 pneumonia who were given different treatments. These included a combination therapy, an antiviral medication only or an antiviral and anti-inflammatory. Almost all patients received treatment with corticosteroids, another common anti-inflammatory medication that is currently part of standard COVID-19 treatment. Patients treated with the antiviral and anti-inflammatory showed more severe pneumonia compared with patients who received just the antiviral, probably reflecting the physicians' choice to give an anti-inflammatory to patients with a more serious clinical condition. Nevertheless, the mortality rate was similar in the two groups. The combination therapy of the antiviral and anti-inflammatory might improve mortality in COVID-19 patients with severe pneumonia to be comparable to mortality in patients with less severe clinical presentations. [ABSTRACT FROM AUTHOR]

Background: The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated. Key Points of the Guidelines Update: Version 12.0 of the guidelines recommend the same six first‐line treatment options for antiretroviral treatment (ART)‐naïve adults as versions 11.0 and 11.1: tenofovir‐based backbone plus an unboosted integrase inhibitor or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. The long‐acting section has been expanded in the ART and drug–drug interaction (DDI) panels. Tables for preferred and alternative ART in children and adolescents have been updated, as has the section on prevention of vertical transmission, particularly with new guidance for breastfeeding. A new DDI table has been included for the ART and anti‐infective drugs used for opportunistic infections, sexually transmitted infections, and other infectious conditions; lenacapavir has been included in all DDI tables. New sections on alcohol use and patient‐reported outcome measures (PROMs) have been included in the comorbidity panel, in addition to updates on many relevant topics, such as new resource guidance for deprescribing in people with HIV. Other sections, including travel, cognitive impairment, cancer screening, sexual health, and diabetes have also been revised extensively. The algorithm for the management of acute hepatitis C virus infection has been removed, as current guidelines recommend immediate treatment of all people with recently acquired hepatitis C virus. Updates on vaccination for hepatitis B virus and recommendations for simplification to tenofovir‐free two‐drug regimens in people with isolated anti‐hepatitis B core antibodies are provided. In the opportunistic infections and COVID‐19 panel, guidance on the management of COVID‐19 in people with HIV has been updated according to the most up‐to‐date evidence, and a new section on monkeypox has been added. Conclusions: In 2023, the EACS guidelines were updated extensively and now include several new sections. The recommendations are available as a free app, in interactive web format, and as a pdf online. [ABSTRACT FROM AUTHOR]