Leveraging international stakeholders' experiences with oral PrEP costs to accelerate implementation of the monthly dapivirine vaginal ring: A qualitative study.

Background: Costing and financing systematic implementation are recognized barriers to human immunodeficiency virus (HIV) prevention. In the absence of empiric implementation and economic data, perspectives from international stakeholders involved in developing and supporting daily oral pre-exposure prophylaxis (PrEP) policy, and programs can provide critical insights for developing costed plans to support and accelerate the rollout of novel long-acting PrEP (LA-PrEP) methods, such as the monthly dapivirine vaginal ring (PrEP ring).

Methods: We interviewed stakeholders from purposively selected international organizations about anticipated PrEP-ring implementation costs, evidence gaps and key process steps for developing a costed rollout plan template (CRPT).

Implementation and resource needs for long-acting PrEP in low- and middle-income countries: a scoping review.

Introduction: Several low- and middle-income countries (LMICs) are preparing to introduce long-acting pre-exposure prophylaxis (LAP). Amid multiple pre-exposure prophylaxis (PrEP) options and constrained funding, decision-makers could benefit from systematic implementation planning and aligned costs. We reviewed national costed implementation plans (CIPs) to describe relevant implementation inputs and activities (domains) for informing the costed rollout of LAP.

Viral delivery of a peptide-based immunomodulator enhances T cell priming during vaccination.

Modern, subunit-based vaccines have so far failed to induce significant T cell responses, contributing to ineffective vaccination against many pathogens. Importantly, while today's adjuvants are designed to trigger innate and non-specific immune responses, they fail to directly stimulate the adaptive immune compartment. Programmed cell death 1 (PD-1) partly regulates naïve-to-antigen-specific effector T cell transition and differentiation by suppressing the magnitude of activation.

A mixed methods study evaluating acceptability of a daily COVID-19 testing regimen with a mobile-app connected, at-home, rapid antigen test: Implications for current and future pandemics.

Background: Widespread use of at-home rapid COVID-19 antigen tests has been proposed as an important public health intervention to interrupt chains of transmission. Antigen tests may be preferred over PCR because they provide on-demand results for relatively low cost and can identify people when they are most likely to be infectious, particularly when used daily. Yet the extent to which a frequent antigen testing intervention will result in a positive public health impact for COVID-19 will depend on high acceptability and high adherence to such regimens.

A Peptide-Based PD1 Antagonist Enhances T-Cell Priming and Efficacy of a Prophylactic Malaria Vaccine and Promotes Survival in a Lethal Malaria Model.

The blockade of programmed cell death-1 (PD1) and its ligand PDL1 has been proven to be a successful immunotherapy against several cancers. Similar to cancer, PD1 contributes to the establishment of several chronic infectious diseases, including malaria. While monoclonal antibodies (mAbs) targeting checkpoint receptors are revolutionary in cancer treatment, the immune-related adverse events (irAEs) may prevent their utilization in prophylactic and therapeutic treatments of infectious diseases.

Novel Peptide-Based PD1 Immunomodulators Demonstrate Efficacy in Infectious Disease Vaccines and Therapeutics.

Many pathogens use the same immune evasion mechanisms as cancer cells. Patients with chronic infections have elevated levels of checkpoint receptors (e.g.

Optical Control of Cytokine Production Using Photoswitchable Galactosylceramides.

α-Galactosylceramides are glycosphingolipids that show promise in cancer immunotherapy. After presentation by CD1d, they activate natural killer T cells (NKT), which results in the production of a variety of pro-inflammatory and immunomodulatory cytokines. Herein, we report the synthesis and biological evaluation of photochromic derivatives of KRN-7000, the activity of which can be modulated with light.

Islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1.

Purpose Of Review: To discuss the potential role of islatravir (ISL), a novel reverse transcriptase translocation inhibitor, in the treatment and prevention of human immunodeficiency virus type 1 (HIV-1) infection.

Recent Findings: Islatravir (4'-ethynyl-2-fluoro-2'-deoxyadenosine, MK-8591) is a long-acting first-in-class nucleoside reverse transcriptase translocation inhibitor with the potential for versatile dosing routes and dosing intervals. It demonstrated robust antiviral activity when dosed once daily and once weekly in HIV-1-infected individuals and SIV-infected rhesus macaques.

Problem-Based Learning Could Tackle the Issue of Insufficient Education and Adherence in People Living With HIV/AIDS.

Poor medication adherence is still the main cause of antiretroviral therapy (ART) failure among people living with HIV/AIDS (PLWHA). Effective behavioral interventions are needed to improve HIV awareness and medication adherence. In this retrospective cohort study, we assessed the effect of problem-based learning (PBL) approaches to HIV-related education and adherence outcomes among PLWHA and a college student sample.

Psychometric Properties and Factor Structure of the Chinese Version of the Hospital Anxiety and Depression Scale in People Living With HIV.

The population of people living with HIV (PLWH) is growing in number and usually results in mental health problems that impact their quality of life. Therefore, valid instruments and screening methods for psychological disorders are of great significance. The Hospital Anxiety and Depression Scale (HADS) reveals good psychometric properties, but shows ambiguous results in factor structure.

Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial.

Background: Cabotegravir (GSK1265744) is an integrase strand transfer inhibitor in development as a long-acting (LA) intramuscular injectable suspension for HIV-1 pre-exposure prophylaxis (PrEP).

Objective: We report participant outcomes from the phase IIa ECLAIR study related to tolerability, acceptability, and satisfaction of cabotegravir LA.

Methods: The ECLAIR study (ClinicalTrials.

No detection of CD4-independent human immunodeficiency virus 1 envelope glycoproteins in brain tissue of patients with or without neurological complications.

Macrophage (mac)-tropic human immnunodeficiency virus type 1 (HIV-1) and simian immnunodeficiency virus (SIV) in brain are associated with neurological disease. Mac-tropic HIV-1 evolves enhanced CD4 interactions that enable macrophage infection via CD4, which is in low abundance. In contrast, mac-tropic SIV is associated with CD4-independent infection via direct CCR5 binding.

Efficacy and Safety of Oral TDF-Based Pre-exposure Prophylaxis for Men Who Have Sex With Men: A Systematic Review and Meta-Analysis.

Pre-exposure prophylaxis (PrEP) is used as an HIV prevention method by people at substantial risk of HIV infection. This systematic review and meta-analysis evaluates current clinical evidence for use of oral TDF-based PrEP among men who have sex with men. A comprehensive literature search in PubMed, web of science, Google Scholar and ClinicalTrials.

The Double Burdens of Mental Health Among AIDS Patients With Fully Successful Immune Restoration: A Cross-Sectional Study of Anxiety and Depression in China.

Anxiety and depression continue to be significant comorbidities for people with HIV infection. We investigated the prevalence of and factors associated with anxiety and depression among adult HIV-infected patients across China. In this cross-sectional study, we described clinical and psychosocial variables related to depression and anxiety in 4103 HIV-infected persons.

From CD4-Based Initiation to Treating All HIV-Infected Adults Immediately: An Evidence-Based Meta-analysis.

Background: The World Health Organization (WHO) Consolidated antiretroviral therapy (ART) guidelines set the CD4 T-cell counts threshold to 500 cells/mm in 2013, and 2015 guidelines recommend treating all HIV-infected adults regardless of their CD4 T-cell counts. To inform the decision-making around ART guidelines for people living with HIV, we systematically reviewed the literature to estimate differences in clinical benefits between individuals starting treatment with baseline CD4 T-cell counts ≥500 cells/mm (early initiation) as compared to <500 cells/mm (deferred initiation).

Methods: We systematically searched the electronic databases and abstracts for randomized controlled trials (RCT) and observational studies.

Molecular Signatures of HIV-1 Envelope Associated with HIV-Associated Neurocognitive Disorders.

Purpose Of Review: The HIV-1 envelope gene (env) has been an intense focus of investigation in the search for genetic determinants of viral entry and persistence in the central nervous system (CNS).

Recent Findings: Molecular signatures of CNS-derived HIV-1 env reflect the immune characteristics and cellular constraints of the CNS compartment. Although more readily found in those with advanced HIV-1 and HIV-associated neurocognitive disorders (HAND), molecular signatures distinguishing CNS-derived quasispecies can be identified early in HIV-1 infection, in the presence or absence of combination antiretroviral therapy (cART), and are dynamic.

Burden of sleep disturbances and associated risk factors: A cross-sectional survey among HIV-infected persons on antiretroviral therapy across China.

This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects.

Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy.

The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation.

Optimization of the Solubility of HIV-1-Neutralizing Antibody 10E8 through Somatic Variation and Structure-Based Design.

Unlabelled: Extraordinary antibodies capable of near pan-neutralization of HIV-1 have been identified. One of the broadest is antibody 10E8, which recognizes the membrane-proximal external region (MPER) of the HIV-1 envelope and neutralizes >95% of circulating HIV-1 strains. If delivered passively, 10E8 might serve to prevent or treat HIV-1 infection.

Lipid and Carbohydrate Modifications of α-Galactosylceramide Differently Influence Mouse and Human Type I Natural Killer T Cell Activation.

The ability of different glycosphingolipids (GSLs) to activate type I natural killer T cells (NKT cells) has been known for 2 decades. The possible therapeutic use of these GSLs has been studied in many ways; however, studies are needed in which the efficacy of promising GSLs is compared under identical conditions. Here, we compare five unique GSLs structurally derived from α-galactosylceramide.

HIV-1 fitness cost associated with escape from the VRC01 class of CD4 binding site neutralizing antibodies.

Unlabelled: Broadly neutralizing antibodies (bNAbs) have been isolated from selected HIV-1-infected individuals and shown to bind to conserved sites on the envelope glycoprotein (Env). However, circulating plasma virus in these donors is usually resistant to autologous isolated bNAbs, indicating that during chronic infection, HIV-1 can escape from even broadly cross-reactive antibodies. Here, we evaluate if such viral escape is associated with an impairment of viral replication.

Viral envelope is a major determinant of enhanced fitness of a multidrug-resistant HIV-1 variant.

Multidrug-resistant (MDR) HIV-1 viruses are thought to be less pathogenic than wild-type viruses because of the fitness costs of drug-resistance mutations. However, we identified an individual infected with MDR virus associated with rapid disease progression referred to as MDR-1. To study the contribution of virologic factors to rapid disease progression, we constructed molecular clones that demonstrated high replication fitness and cytopathicity.