Effectiveness, safety, and patient-reported outcomes of bictegravir/emtricitabine/tenofovir alafenamide in routine clinical care in Italy: 12-Month results from the BICSTaR cohort.

Background: BICSTaR is a multi-national, observational cohort evaluating the effectiveness, safety, and patient-reported outcomes (PROs) in treatment-naïve (TN) and -experienced (TE) people with HIV-1 receiving bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in routine clinical care. We present the 12-month (M12) outcomes of the Italian BICSTaR cohort.

Methods: Participants initiating B/F/TAF in routine care were prospectively followed.

Clinical Pharmacology of the Single Tablet Regimen Bictegravir/Emtricitabine/Tenofovir Alafenamide in the evolving era of antiretroviral therapies.

In this fast-evolving era of antiretroviral chemotherapy, the single-tablet regimen (STR) BIC/FTC/TAF, an oral regimen including a potent INSTI (strand-transfer integrase inhibitors) like Bictegravir plus two different NRTIs (Nucleoside Reverse Transcriptase Inhibitors), is increasingly challenged by new oral combinations. Furthermore, long-acting injectable drugs have also been developed and others are being under development. Notably, no new STR consisting of two NRTIs plus a 3rd drug like an INSTI are in the industrial pipeline.

Central Nervous System Disorders with Auto-Antibodies in People Living with HIV.

People living with HIV (PLWH) may present atypical neurological complications. Recently, autoimmune manifestations of the central nervous system (CNS) have been described. We retrospectively described the features of PLWH presenting with acute neurological symptoms with positive anti-CNS antibodies.

Symptomatic and Asymptomatic Neurocognitive Impairment, ART Adherence and HIV Control: A 4-Year Observational Study.

We assessed whether symptomatic neurocognitive impairment (NCI) and asymptomatic NCI -of which the clinical relevance is debated- affect HIV control and the role of ART adherence in this relationship. Observational study on the relationship between NCI and viral control during the 2 years before and the 2 after the neurocognitive evaluation (NCE) of 322 PLWH on ART. Viral load (VL) was defined as undetectable, very low-level (VLLV), low-level (LLV), or high-level viremia (HLV), and classified overtime as persistent (p; ≥2 consecutive values in the same worst category), viral failure (VF; ≥1 HLV requiring ART changes), or optimal control.

Studying the Changes in Physical Functioning and Oxidative Stress-Related Molecules in People Living with HIV after Switching from Triple to Dual Therapy.

Background: Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy.

Host single nucleotide polymorphisms and biomarkers of neuronal damage and inflammation in people living with HIV.

Objectives: Blood-brain barrier impairment is frequent in people living with human immunodeficiency virus (PLWHIV), affecting the penetration of target cells and antiretrovirals into the central nervous system, through transporters (e.g. ABCB1), leading to neuroinflammation.

HBsAg kinetics after 7 years of therapy with tenofovir disoproxil fumarate in a cohort of naïve patients affected by chronic hepatitis B with different genotypes.

The role of different genotypes in nucleos(t)ide analogs (NAs) treatment is still debated. Previous studies conducted on special populations evidenced that the E genotype had the lower virological and serological response. This descriptive study aims to recognize the hepatitis B "s" antigen (HBsAg) decline during tenofovir disoproxil fumarate (TDF) treatment in a cohort of patient affected by chronic hepatitis B (CHB).

Pharmacological outlook of Lenacapavir: a novel first-in-class Long-Acting HIV-1 Capsid Inhibitor.

The evolution of antiretroviral therapy is now addressed to develop regimens consisting of two instead of three drugs and it is also increasingly oriented to develop long-acting parenteral formulations in order to increase treatment adherence and to reduce the multifaceted individual burden associated to daily intake of drugs. This new way was first paved by the dual association consisting of the INSTI Cabotegravir and the NNRTI Rilpivirine, whose formulations allow for a single administration every two months. In 2022 a new drug with a novel mechanism of action and a longer persistence of effective drug concentrations was made available in many countries for the treatment of drug-resistant HIV infection in association to other antiretrovirals.

Intrathecal production of anti-Epstein-Barr virus viral capsid antigen IgG is associated with neurocognition and tau proteins in people with HIV.

Objective: HIV and Epstein-Barr virus (EBV) co-infection has been linked to increased immune activation and larger HIV reservoir. We assessed whether anti-EBV humoral responses are associated with increased cerebrospinal fluid (CSF) inflammation and with neurocognitive impairment (NCI) in people with HIV (PWH).

Design: Cross-sectional analysis in 123 EBV-seropositive PWH either on antiretroviral therapy ( n  = 70) or not.

Parietal resting-state EEG alpha source connectivity is associated with subcortical white matter lesions in HIV-positive people.

Objective: Parietal resting-state electroencephalographic (rsEEG) alpha (8-10 Hz) source connectivity is abnormal in HIV-positive persons. Here we tested whether this abnormality may be associated with subcortical white matter vascular lesions in the cerebral hemispheres.

Methods: Clinical, rsEEG, and magnetic resonance imaging (MRI) datasets in 38 HIV-positive persons and clinical and rsEEG datasets in 13 healthy controls were analyzed.

Clinical pharmacology of the SingleTablet Regimen (STR) Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF).

In Italy a proportion of HIV patients exceeding 50% are diagnosed at advanced stages of disease. A sizeable proportion of patients under chronic HIV treatment has a story of poor adherence with archived resistance associated mutations, a condition implying some risks in case of treatment with dual regimens. Conventional three-drug regimens will remain necessary in the short-mid term, in order to avoid treatment failure and selection of drug resistance.

Pillars of long-term antiretroviral therapy success.

Background: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies.

Methods: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care.

Results: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life.

Real-life comparison of mortality in patients with SARS-CoV-2 infection at risk for clinical progression treated with molnupiravir or nirmatrelvir plus ritonavir during the Omicron era in Italy: a nationwide, cohort study.

Background: Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era.

Methods: Data collected in the nationwide, population-based, cohort of patients registered in the database of the Italian Medicines Agency (AIFA) were used.

Extended and Continuous Infusion of Novel Protected β-Lactam Antibiotics: A Narrative Review.

Consolidated data from pharmacokinetic and pharmacodynamic studies support the administration of β-lactam antibiotics in prolonged infusion (i.e., extended or continuous) to optimize therapeutic efficacy by increasing the probability of attaining maximal bactericidal activity.

COVID-19: A Possible Contribution of the MAPK Pathway.

Background: COVID-19 is characterized by an uncontrolled inflammatory response with high pro-inflammatory cytokine production through the activation of intracellular pathways, such as mitogen-activated protein kinase (MAPK). Viruses are able to exploit the MAPK pathway to their advantage; this pathway relevance to severe COVID-19 is poorly described. The aim of this study was to quantify biomarkers involved in the MAPK pathway and to clarify its possible role in affecting some COVID-19-related clinical features.

COVID-19: Focusing on the Link between Inflammation, Vitamin D, MAPK Pathway and Oxidative Stress Genetics.

An uncontrolled inflammatory response during SARS-CoV-2 infection has been highlighted in several studies. This seems to be due to pro-inflammatory cytokines whose production could be regulated by vitamin D, ROS production or mitogen-activated protein kinase (MAPK). Several genetic studies are present in the literature concerning genetic influences on COVID-19 characteristics, but there are few data on oxidative stress, vitamin D, MAPK and inflammation-related factors, considering gender and age.

Cerebrospinal Fluid CXCL13 as Candidate Biomarker of Intrathecal Immune Activation, IgG Synthesis and Neurocognitive Impairment in People with HIV.

Plasma C-X-C-motif chemokine ligand-13 (CXCL13) has been linked to disease progression and mortality in people living with HIV (PLWH) and is a candidate target for immune-based strategies for HIV cure. Its role in central nervous system (CNS) of PLWH has not been detailed. We described CSF CXCL13 levels and its potential associations with neurological outcomes.

Analytical validation of a novel UHPLC-MS/MS method for 19 antibiotics quantification in plasma: Implementation in a LC-MS/MS Kit.

Background: Therapeutic drug monitoring (TDM) for antibiotic drugs represents a consolidated practice to optimize the effectiveness and to limit the toxicity of specific drugs by guiding dosage adjustments. The comparison of TDM results with drug-specific pharmacokinetic/pharmacodynamic (PK/PD) parameters, based on killing dynamics and bacterial susceptibility, increases the probability of therapeutic success.

Purpose: The aim of this study was the analytical validation of a new UHPLC-MS/MS assay for the quantification of 19 antibiotics divided in two different sets considering their chemical/pharmacological properties.

Antiretroviral Levels in the Cerebrospinal Fluid: The Effect of Inflammation and Genetic Variants.

Neurocognitive impairments are common in people living with HIV. Some conditions, such as chronic inflammation, astrocyte infection and an impaired blood-brain barrier (BBBi), along with host genetic variants in transporter genes, may affect antiretroviral (ARV) exposure in the cerebrospinal fluid (CSF). The aim of this study was to evaluate ARV CSF penetration according to compartmental inflammation, BBB permeability and single-nucleotide polymorphisms (SNPs) in drug transporter encoding genes.