Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine.

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV).

Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI.

Results: Among the 395 PLWH receiving RPV, 180 (45.

Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases.

By binding to multiple antigens simultaneously, multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass of antibody-based constructs, consist of engineered structures designed to bridge immune effector cells to their target, thereby redirecting the immune response toward the tumor cells or infected cells. The increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and infections.

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe.

Background: Investigating the role of late presenters (LPs) in HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus before diagnosis, when they are not aware of their HIV status.

Objective: To characterize individuals living with HIV-1 followed up in Europe infected with subtypes A, B, and G and to compare transmission clusters (TC) in LP vs. non-late presenter (NLP) populations.

Incarceration history is associated with HIV infection among community-recruited people who inject drugs in Europe: A propensity-score matched analysis of cross-sectional studies.

Aims: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe.

Design, Setting And Participants: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months).

Multimeric immunotherapeutic complexes activating natural killer cells towards HIV-1 cure.

Background: Combination antiretroviral therapy (cART) has dramatically extended the life expectancy of people living with HIV-1 and improved their quality of life. There is nevertheless no cure for HIV-1 infection since HIV-1 persists in viral reservoirs of latently infected CD4 T cells. cART does not eradicate HIV-1 reservoirs or restore cytotoxic natural killer (NK) cells which are dramatically reduced by HIV-1 infection, and express the checkpoint inhibitors NKG2A or KIR2DL upregulated after HIV-1 infection.

Validation of a SARS-CoV-2 Surrogate Neutralization Test Detecting Neutralizing Antibodies against the Major Variants of Concern.

SARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron BA.

Vaccine- and Breakthrough Infection-Elicited Pre-Omicron Immunity More Effectively Neutralizes Omicron BA.1, BA.2, BA.4 and BA.5 Than Pre-Omicron Infection Alone.

Since the emergence of SARS-CoV-2 Omicron BA.1 and BA.2, several Omicron sublineages have emerged, supplanting their predecessors.

The anti-caspase 1 inhibitor VX-765 reduces immune activation, CD4 T cell depletion, viral load, and total HIV-1 DNA in HIV-1 infected humanized mice.

HIV-1 infection results in the activation of inflammasome that may facilitate viral spread and establishment of viral reservoirs. We evaluated the effects of the caspase-1 inhibitor VX-765 on HIV-1 infection in humanized NSG mice engrafted with human CD34 hematopoietic stem cells. Expression of caspase-1, NLRP3, and IL-1β was increased in lymph nodes and bone marrow between day 1 and 3 after HIV-1 infection (mean fold change (FC) of 2.

Liver Disease and Treatment Needs of Asymptomatic Persons Living With Hepatitis B in Senegal.

The prevalence of active hepatitis B among asymptomatic persons remains unclear in Africa. Of 1206 newly diagnosed persons in Senegal, 12.3% had significant fibrosis and 31.

Impact of COVID-19 & Response Measures on HIV-HCV Prevention Services and Social Determinants in People Who Inject Drugs in 13 Sites with Recent HIV Outbreaks in Europe, North America and Israel.

HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011-2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020.

Imprint of Initial Education and Loss of Ly49C/I in Activated Natural Killer Cells of TAP1-KO and C57BL/6 Wildtype Mice.

Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of their major histocompatibility complex class I molecules with self-specific inhibitory receptors that recognize them. In the absence of such contacts, caused by either the lack of expression of the inhibitory receptors or a very low level of major histocompatibility complex class I (MHC class I) proteins, NK cells are hypo-reactive at baseline ().

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone.

SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.

Trends of Transmitted and Acquired Drug Resistance in Europe From 1981 to 2019: A Comparison Between the Populations of Late Presenters and Non-late Presenters.

Background: The increased use of antiretroviral therapy (ART) has decreased mortality and morbidity of HIV-1 infected people but increasing levels of HIV drug resistance threatens the success of ART regimens. Conversely, late presentation can impact treatment outcomes, health costs, and potential transmission of HIV.

Objective: To describe the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in HIV-1 infected patients followed in Europe, to compare its patterns in late presenters (LP) vs non-late presenters (NLP), and to analyze the most prevalent drug resistance mutations among HIV-1 subtypes.

Analysis of the Origin and Dissemination of HIV-1 Subtype C in Bulgaria.

HIV-1 subtype C is the most abundant strain of HIV-1 infections worldwide and was found in the first known patients diagnosed with HIV/AIDS in Bulgaria in 1986. However, there is limited information on the molecular-epidemiological characteristics of this strain in the epidemic of the country. In this study, we analyze the evolutionary history of the introduction and dissemination of HIV-1 subtype C in Bulgaria using global phylogenetic analysis, Bayesian coalescent-based approach, and molecular clock methods.

Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe.

Objectives: To explore the effectiveness and durability of integrase strand transfer inhibitor (INSTI)-based regimens in pre-treated subjects.

Methods: Treatment-experienced individuals starting an INSTI-based regimen during 2012-2019 were selected from the INTEGRATE collaborative study. The time to virological failure [VF: one measurement of viral load (VL) ≥ 1000 copies/mL or two ≥ 50 copies/ml or one VL measurement ≥ 50 copies/mL followed by treatment change] and to INSTI discontinuation were evaluated.

The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures.

Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is key since DAA failure is rare and real-life data are scattered.

Determinants of HIV-1 Late Presentation in Patients Followed in Europe.

To control the Human Immunodeficiency Virus (HIV) pandemic, the World Health Organization (WHO) set the 90-90-90 target to be reached by 2020. One major threat to those goals is late presentation, which is defined as an individual presenting a TCD4+ count lower than 350 cells/mm or an AIDS-defining event. The present study aims to identify determinants of late presentation in Europe based on the EuResist database with HIV-1 infected patients followed-up between 1981 and 2019.

Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-naive individuals: results from a European multi-cohort study.

Background: INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care.

Objectives: We analysed ART-naive patients who started INSTI-based regimens in 2012-19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts.

Active Components from Prevent HIV-1 Entry by Distinct Mechanisms of Action.

is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of , and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone.