ADAR1 function affects HPV replication and is associated to recurrent human papillomavirus-induced dysplasia in HIV coinfected individuals.

Infection by human papillomavirus (HPV) alters the microenvironment of keratinocytes as a mechanism to evade the immune system. A-to-I editing by ADAR1 has been reported to regulate innate immunity in response to viral infections. Here, we evaluated the role of ADAR1 in HPV infection in vitro and in vivo.

HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection.

HIV Nef is a central auxiliary protein in HIV infection and pathogenesis. Our results indicate that HDAC6 promotes the aggresome/autophagic degradation of the viral polyprotein Pr55Gag to inhibit HIV-1 production. Nef counteracts this antiviral activity of HDAC6 by inducing its degradation and subsequently stabilizing Pr55Gag and Vif viral proteins.

Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa.

HIV viral reservoirs are established very early during infection. Resident memory T cells (T) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4T display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities.

Meeting report: 32nd International Conference on Antiviral Research.

The 32nd International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held in Baltimore, Maryland, USA, on May 12-15, 2019. This report gives an overview of the conference on behalf of the Society. It provides a general review of the meeting and awardees, summarizing the presentations, and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development.

Different pattern of stool and plasma gastrointestinal damage biomarkers during primary and chronic HIV infection.

Introduction: Primary HIV infection (PHI) is the initial phase after HIV acquisition characterized by high viral replication, massive inflammatory response and irreversible immune-damage, particularly at the gastrointestinal level. In this study we aimed to characterize the dynamics of gastrointestinal damage biomarkers during the different phases of HIV infection and assess their association with HIV-disease markers and their accuracy to differentiate PHI from chronic HIV infection (CHI).

Methods: PHI-individuals (n = 57) were identified as HIV-seronegative/HIV-RNA positive and were followed up for one year at the Manhiça District Hospital in Mozambique.

Attachment Styles, Condomless Sex, and Drugs in HIV-Positive Gay and Bisexual Men.

This study evaluated whether attachment styles might be related to condomless sex, use of drugs, and adherence to antiretroviral treatment (ART) in 400 HIV-positive gay and bisexual men (GBM). With the Relationship Questionnaire, 160 men were classified as securely attached and 240 as insecurely attached (88 dismissive, 79 preoccupied, and 73 fearful). Insecurely attached GBM had more condomless sex ( = 0.

Dual effect of the broad spectrum kinase inhibitor midostaurin in acute and latent HIV-1 infection.

Midostaurin is a multi-kinase inhibitor with antineoplastic activity. We assessed the capacity of midostaurin to affect early and late steps of HIV-1 infection and to reactivate HIV-1 latently infected cells, alone or in combination with histone deacetylase inhibitors (HDACi) known to act as latency-reversing agents (LRA). Acute HIV-1 infection was assessed by flow cytometry in three cell types treated with midostaurin in the presence or absence of SAMHD1.

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.

Background: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships.

Methods: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries.

Increasing Diagnostic Uncertainties in Children With In Utero HIV Infection.

We present a case of an in utero HIV-infected child, who on day 1 of life had a positive whole blood total nucleic acid test but viral load <20 RNA copies/mL. Dried blood spot total nucleic acid testing was negative on day 1, 10 and at 3 months, while on ART prophylaxis then positive at 5 months after prophylaxis ended. Retrospective peripheral blood mononuclear cells HIV DNA testing from day 1 of life was positive, confirming in utero infection.

Glutaminolysis and lipoproteins are key factors in late immune recovery in successfully treated HIV-infected patients.

The immunological, biochemical and molecular mechanisms associated with poor immune recovery are far from known, and metabolomic profiling offers additional value to traditional soluble markers. Here, we present novel and relevant data that could contribute to better understanding of the molecular mechanisms preceding a discordant response and HIV progression under suppressive combined antiretroviral therapy (cART). Integrated data from nuclear magnetic resonance (NMR)-based lipoprotein profiles, mass spectrometry (MS)-based metabolomics and soluble plasma biomarkers help to build prognostic and immunological progression tools that enable the differentiation of HIV-infected subjects based on their immune recovery status after 96 weeks of suppressive cART.

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic.

In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4 T cell counts. HIV-1 envelope glycoprotein complex (Env) is a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function in this rare clinical phenotype.

Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting.

Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks.

Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia.

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CART fratricide. CD1a is exclusively expressed in cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained at relapse.

Approach to amoebic colitis: Epidemiological, clinical and diagnostic considerations in a non-endemic context (Barcelona, 2007-2017).

Background: Amoebic colitis is the most frequent clinical manifestation of invasive intestinal infection due to Entamoeba histolytica and a common cause of diarrhoea worldwide. Since higher transmission rates are usually related to poor health and exposure to unhygienic conditions, cases reported in Europe usually involve immigrants and international travellers. The goal of this study was to characterise both the clinical and the epidemiological features of a European population diagnosed with amoebic colitis and then to evaluate the diagnostic tools and therapeutic options applied.

Switching From a Protease Inhibitor-based Regimen to a Dolutegravir-based Regimen: A Randomized Clinical Trial to Determine the Effect on Peripheral Blood and Ileum Biopsies From Antiretroviral Therapy-suppressed Human Immunodeficiency Virus-infected Individuals.

Background: Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy.

Methods: Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group).

Cancer immunotherapy of patients with HIV infection.

Cancer immunotherapy with antibodies against immune checkpoints has made impressive advances in the last several years. The most relevant drugs target programmed cell death 1 (PD-1) expressed on T cells or its ligand, the programmed cell death ligand 1 (PD-L1), expressed on cancer cells, and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Unfortunately, cancer patients with HIV infection are usually excluded from cancer clinical trials, because there are concerns about the safety and the anti-tumoral activity of these novel therapies in patients with HIV infection.

Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages.

Macrophages are natural target cells of human immunodeficiency virus type 1 (HIV-1). Viral replication appears to be delayed in these cells compared to lymphocytes; however, little is known about the kinetics of early post-entry events. Time-of-addition experiments using several HIV-1 inhibitors and the detection of reverse transcriptase (RT) products with droplet digital PCR (ddPCR) revealed that early replication was delayed in primary human monocyte-derived macrophages of several donors and peaked late after infection.

Awareness, knowledge, use, willingness to use and need of Pre-Exposure Prophylaxis (PrEP) during World Gay Pride 2017.

Objective: To assess the awareness, knowledge, use, and willingness to use and need of PrEP among men who have sex with men (MSM) and transgender women (TW) who attended World Gay Pride (WGP) 2017 in Madrid.

Design And Methods: Online survey. Participants were recruited through gay-oriented dating apps and HIV Non-Governmental Organizations´ social media.

Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice.

The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown.

Incidence of cervical high-grade squamous intraepithelial lesions in HIV-1-infected women with no history of cervical pathology: up to 17 years of follow-up.

Currently, Papanicolaou smears are proposed at three-year intervals for cervical screening to all women living with HIV. The aim of this retrospective cohort study was to provide data on the incidence of cervical high-grade squamous intraepithelial lesions (HSIL) in cervical smear confirmed by histology in HIV-1-infected women (two consecutive normal Papanicolaou smears at baseline) after a long-term follow-up. Sixty-seven women (recruited between March 1999 and January 2003) were analyzed.

High Prevalence of Sarcopenia in HIV-Infected Individuals.

Background: Sarcopenia is a geriatric syndrome that leads to a loss of functionality and mortality.

Methods: We assessed the prevalence of sarcopenia in HIV-infected patients attended in our HIV Unit who had at least two DXA scans from 2000 to 2016 (1,720 DXA scans from 860 individuals). Sarcopenia was determinate according to appendicular skeletal muscle mass index (ASM) calculated as the ratio between skeletal muscle mass index (SMI) by DXA and height (kg/m).

Meeting report: 31 International Conference on Antiviral Research.

The 31 International Conference on Antiviral Research (ICAR) was held in Porto, Portugal from June 11-15, 2018. In this report, volunteer rapporteurs provide their summaries of scientific presentations, hoping to effectively convey the speakers' goals and the results and conclusions of their talks. This report provides an overview of the invited keynote and award lectures and highlights of short oral presentations, from the perspective of experts in antiviral research.

CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir.

CD32 has been shown to be preferentially expressed in latently HIV-1-infected cells in an in vitro model of quiescent CD4 T cells. Here we show that stimulation of CD4+ T cells with IL-2, IL-7, PHA, and anti-CD3/CD28 antibodies induces T-cell proliferation, co-expression of CD32 and the activation of the markers HLA-DR and CD69. HIV-1 infection increases CD32 expression.

ADAR1 affects HCV infection by modulating innate immune response.

The hepatitis C virus (HCV) is a globally prevalent infectious pathogen. As many as 80% of people infected with HCV do not control the virus and develop a chronic infection. Response to interferon (IFN) therapy is widely variable in chronic HCV infected patients, suggesting that HCV has evolved mechanisms to suppress and evade innate immunity responsible for its control and elimination.

Impact of intensification with raltegravir on HIV-1-infected individuals receiving monotherapy with boosted PIs.

Background: Monotherapy with ritonavir-boosted PIs (PI/r) has been used to simplify treatment of HIV-1-infected patients. In previous studies raltegravir intensification evidenced ongoing viral replication and reduced T cell activation, preferentially in subjects receiving PI-based triple ART. However, data about low-level viral replication and its consequences in patients receiving PI/r monotherapy are scarce.