Patrick W G Mallon's research while affiliated with St. Vincent’s Hospital, Fairview and other places
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Publications (176)
Introduction: As people living with HIV age, the increasing burden of multimorbidity poses a significant health challenge. The aims of this study were to identify common patterns of multimorbidity and examine changes in their burden, as well as their associations with risk factors, over a 3–5 year period in people with HIV, enrolled in the Pharmaco...
Background:
Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined.
Objectives:
We investigated EC activation in patients with acute...
A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infectivity, using physiologically relevant models of the human bronchial epithelium, to model earl...
Purpose of review:
The purpose of this article is to review alterations in microbiota composition, diversity, and functional features in the context of chronic inflammation and comorbidities associated with HIV infection.
Recent findings:
The gut microbiome is an important mediator of host immunity, and disruption of gut homeostasis can contribu...
Background
Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated post-infection/post-vaccination.
Here we describe a novel medium-throughput flow cytometry based micro-neutralisation assay to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-...
Background
Which components of the immune response to SARS-CoV-2 vaccination best protect against subsequent infection remains unclear. We explored SARS-CoV-2 specific antibody and B-cell responses post 3rd dose vaccine and their relationship to subsequent SARS-CoV-2 infection.
Methods
In a multicentre prospective cohort, adult subjects provided s...
Background
Long COVID is a heterogenous condition. We previously demonstrated distinct phenotypes of long COVID, but the impact of later waves caused by SARS-CoV-2 variants on long COVID presentations has not been described.
Methods
We selected individuals with ongoing symptoms > 4 weeks from PCR-confirmed COVID-19 in a multicentre, prospective co...
Background
A wide array of assays to detect the serologic response to SARS-CoV-2 have been developed since the emergence of the pandemic. The majority of these are either qualitative or semi-quantitative, detect antibodies against one antigenic target, and are not adaptable to new antigens.
Methods
We developed a new, multiplex immunoassay to dete...
Background:
People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk.
Methods:
We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: 'gut/immune activation', 'neurovascular', and 'refe...
Background:
Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2.
Search methods:
We searched the Cochra...
Background:
The pan-European VACCELERATE network aims to implement the first transnational harmonised and sustainable vaccine trial Volunteer Registry, serving as single entry-point for volunteers willing to participate in large scale vaccine clinical studies across the European region. The present work exhibits a set of harmonised vaccine trial e...
Background/Objectives
People with obesity (PWO) face an increased risk of severe outcomes from COVID-19, including hospitalisation, ICU admission and death. Obesity has been seen to impair immune memory following vaccination against influenza, hepatitis B, tetanus, and rabies. Little is known regarding immune memory in PWO following COVID-19 adenov...
Background
Monitoring systems have been developed during the COVID-19 pandemic enabling clinicians to remotely monitor physiological measures including pulse oxygen saturation (SpO2), heart rate (HR), and breathlessness in patients after discharge from hospital. These data may be leveraged to understand how symptoms vary over time in COVID-19 patie...
Background: We aim to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with a new diagnosis of HIV and advanced immune suppression in Malawi, and whether they associated with arterial stiffness.
Methods : Microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) were carried out...
A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSA...
Study Objectives
We investigated associations between inflammatory profiles/clusters and sleep measures in people living with HIV and demographically-/lifestyle-similar HIV-negative controls in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY)-Sleep sub-study.
Methods
Primary outcome was insomnia (Insomnia Severity Index [...
Objective:
Both obesity and HIV infection are characterized by a state of chronic inflammation associated with increased morbidity and mortality. This review aims to assess the available literature on immune dysregulation in obesity and people with HIV infection (PWH).
Design:
A systematic review of peer-reviewed literature.
Methods:
We conduc...
Background/Objectives: People with obesity (PWO) face an increased risk of severe outcomes from COVID19, including hospitalisation, ICU admission and death. Obesity has been seen to impair immune memory following vaccination against influenza, hepatitis B, tetanus, and rabies. Little is known regarding immune memory in PWO following COVID19 adenovi...
Measurement of quantitative antibody responses are increasingly important in evaluating the immune response to infection and vaccination. In this study we describe the validation of a quantitative, multiplex serologic assay utilising an electrochemiluminescence platform, which measures IgG against the receptor binding domain (RBD), spike S1 and S2...
Background:
Prolonged recovery is common after SARs-CoV-2 infection, however the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF-ADAMTS13 imbalance, dysregulated angiogenesis and immuno-thrombosis are hallmarks of acute COVID-19. We hypothesized that VWF-ADAMTS13 imbalance persists in convalescence together with...
Introduction
The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study...
Objective:
Obesity is a major risk factor for severe disease in COVID-19, with increased hospitalization, ICU admission and mortality. This increased impact of COVID-19 in people with obesity (PWO) is likely driven, in part, by the well described obesity-induced immune dysregulation. Obesity has also been associated with impaired immune memory in...
Introduction
Sleep problems are commonly reported in people with HIV (PWH) and may be exacerbated by HIV-induced inflammation. We determined associations between systemic inflammation and objective/subjective sleep measures in PWH and demographically/lifestyle similar HIV-negative controls.
Methods
Objective sleep measures from 7-day actigraphy (e...
Coronavirus disease 2019 (COVID-19) pandemic has demonstrated
how vaccines play a key role in the fight against infectious diseases. However,
identifying suitable study subjects can be challenging in clinical trials. Therefore,
within the VACCELERATE Consortium, a volunteer registry for vaccine trial
participation has been established. VACCELERATE’...
Background
We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID.
Methods
This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of a...
Background
Interleukin-6 (IL-6) is elevated in SARS-CoV-2 infection. IL-6 regulates acute-phase proteins, such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the protease-anti-protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS) compared to non-SARS-CoV-2 AR...
Background:
The European AIDS Clinical Society (EACS) Guidelines were revised in 2021 for the 17th time with updates on all aspects of HIV care.
Key points of the guidelines update:
Version 11.0 of the Guidelines recommend six first-line treatment options for antiretroviral treatment (ART)-naïve adults: tenofovir-based backbone plus an unboosted...
Background
It is the investigator’s responsibility to communicate the relevant information about a clinical trial to participants before they provide informed consent to take part. Systematic reviews indicate that participants often have a poor understanding of the concepts which are key to ensuring valid informed consent, such as randomisation and...
Background
Increases in lipids have been observed in people living with HIV (PLWH) switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We assessed changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) following a switch from TDF to TAF.
Methods
Adults with ≥1 lipid measure before and after swi...
Purpose of review:
Cardiovascular diseases (CVD) is one of the leading cause of morbidity and mortality in antiretroviral treated people living with HIV (PWH) with risk score algorithms based on traditional risk factors being shown to be consistently unreliable in estimating risk in this population. This review aims to examine recent data publishe...
Introduction : Saliva represents a less invasive alternative to nasopharyngeal swab (NPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. SalivaDirect is a nucleic acid extraction-free method for detecting SARS-CoV2 in saliva specimens. Studies evaluating the concordance of gold standard NPS and newly developed SalivaDir...
Background: We aimed to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with human immunodeficiency virus (HIV) and advanced immune suppression in Malawi, and whether they associated with arterial stiffness.
Methods: Antiretroviral therapy (ART)-naïve adults with a new HIV diagnosis and CD4 <100 ce...
Background and Objective
Many people living with HIV (PLWH) on stable tenofovir disoproxil fumarate (TDF)-containing regimens have switched to tenofovir alafenamide (TAF), despite the potential lipid-lowering effect of TDF. We aimed to assess the impact of switching from TDF to TAF on lipids in real-world clinical practice.MethodsPLWH prescribed TD...
Background
Non-communicable diseases (NCDs) are increased amongst people living with HIV (PLWH) and are driven by persistent immune activation. The role of socioeconomic status (SES) in immune activation amongst PLWH is unknown, especially in low-income sub-Saharan Africa (SSA), where such impacts may be particularly severe.
Methods
We recruited M...
Background
Persistent symptoms including breathlessness, fatigue and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this ‘Long COVID’ syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascul...
Introduction : Saliva represents a less invasive alternative to nasopharyngeal swab (NPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. SalivaDirect is a nucleic acid extraction-free method for detecting SARS-CoV2 in saliva specimens. Studies evaluating the concordance of gold standard NPS and newly developed SalivaDir...
Objectives:
To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH).
Methods:
Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study...
Background : COVID- 19 confers an increased risk of thrombosis however the mechanisms underlying this coagulopathy and the optimal approach to thromboprophylaxis are unknown. Thrombotic risk is likely greatest among patients with severe COVID- 19 requiring critical organ support however patients with moderate disease may be at risk and might also b...
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 100 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with...
Background
In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had c...
Introduction: Tocilizumab is one of the main repurposed therapies investigated for COVID-19 pneumonia since the start of the pandemic, but there has been conflicting evidence for its use.
Areas covered: This review covers the physiology of interleukin-6 and its role in the pathophysiology of COVID-19. We discuss the use of tocilizumab in other dise...
Background:
Consistent with fulminant endothelial cell activation, elevated plasma von Willebrand factor (VWF) antigen levels have been reported in patients with COVID-19. The multimeric size and function of VWF are normally regulated through ADAMTS13-mediated proteolysis.
Objective:
This study investigated the hypothesis that ADAMTS13 regulatio...
Purpose of review:
People living with HIV (PWH) are at greater risk of low bone mineral density (BMD) and fractures compared to the general population. This narrative review summarises recent literature in the field, including the relative contribution of antiretroviral therapy and frailty to low BMD and fractures in PWH.
Recent findings:
The bo...
Background
Although reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood.
Methods
Within a large, well-phenotyped, diverse, prospective cohort of subje...
The interferon lambda (IFNL) single nucleotide polymorphism
(SNP) rs368234815 has been associated with altered host responses to
viral infection. We aimed to determine its impact on CD4:CD8 T-cell ratio
normalisation in people with HIV (PWH).
LINKED CONTENT
This article is linked to Taxonera et al paper. To view this article, visit https://doi.org/10.1111/apt.15804
Objectives:
To evaluate the agreement between self-reported sleep measures and insomnia with objectively-measured sleep parameters in people with HIV (PWH) and HIV-negative individuals.
Design:
Cross-sectional analysis of PWH and lifestyle-similar HIV-negative individuals.
Methods:
Self-reported measures included time spent in bed, sleep onset...
Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associ...
Study objectives:
We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches.
Methods:
Cognitive and 7-day/night actigraphy data were co...
Background: Whole-genome sequencing (WGS) of SARS-CoV-2 laboratory-confirmed cases can provide insights into viral transmission and genetic diversity at a population level. However, less is known about the impact of non-pharmaceutical interventions (NPIs), including lockdowns, on circulating SARS-CoV-2 lineages and variants of concern, the relative...
We investigated the correlations and agreement between cognitive assessments made using a computerised (CogState™, six domains) and a standard pen-and-paper battery (five domains) in PWH and lifestyle-similar HIV-negative individuals. Demographically adjusted domain and global T-scores were obtained and used to define cognitive impairment according...
The COVID-19 pandemic is an unprecedented global challenge that substantially risks reversing the progress in ending HIV. At the same time, it may offer the opportunity for a new era of HIV management. This viewpoint presents the impact of COVID-19 on HIV care, including the Joint United Nations Programme on HIV/AIDS (UNAIDS) “three 90s” targets. I...
Background
Self-reported sleep quality is poor in persons with HIV (PWH), but prior studies used non-specific questionnaires, investigated only single sleep disorders, or lacked HIV-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a pandemic infection in 2020 has presented many therapeutic challenges. Not least among these is the importance of abnormal host response to infection that is one of the main drivers of more severe disease. Despite significant research endeavours, very few effective th...
Objectives
Tocilizumab is a humanized monoclonal antibody which targets and inhibits interleukin-6 (IL-6) and has demonstrated efficacy in treating diseases associated with hyper-inflammation. Data are suggestive of tocilizumab as a potential treatment for patients with COVID-19 infection. The aim of this study is to determine the safety and effica...
Objective:
To investigate the prevalence of widespread pain among people with HIV (PWH) and describe associations with antiretroviral therapy (ART) and markers of HIV disease stage.
Design:
Cross-sectional analysis of cohort study in the United Kingdom and Ireland.
Methods:
Pain information was collected during the baseline visit (conducted fr...
Background
Although guidelines for the management of HIV infection include recommendations for aging people living with HIV (PLWH), clinical practice of European HIV care providers may vary.Method
We performed a study using a 3-phase Delphi methodology by involving a panel of clinicians with expertise in HIV infection clinical management. The main...
The original version of this article unfortunately contained a mistake.
Objective:
To determine comorbidity indices in persons-with-HIV (PWH) and lifestyle-similar HIV-negative controls.
Design:
Cross-sectional analysis of the Pharmacokinetic and clinical Observations in PeoPle over fifty (POPPY) cohort study in UK and Ireland.
Methods:
The Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index (CCI) and t...
Background:
The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in...
Background:
Whilst reporting improved renal and bone safety profiles, studies have noted changes in lipid profiles among people living with HIV (PLWH) receiving antiretroviral therapy (ART) switching away from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We aimed to characterize changes in lipids observed after switching to...
Background:
Inflammation drives vascular dysfunction in HIV, but in low-income settings causes of inflammation are multiple, and include infectious and environmental factors. We hypothesised that patients with advanced immunosuppression could be stratified into inflammatory phenotypes that predicted changes in vascular dysfunction on ART.
Methods...
: Associations between markers of liver and renal dysfunction and NRTI plasma exposure are ill-defined. As part of a large cohort study (POPPY), we analysed associations between ALT and eGFR results in people living with HIV on tenofovir (TFV) disoproxil fumarate (TDF), emtricitabine (FTC), abacavir (ABC) and lamivudine (3TC). While we found no ass...
One of the most explored therapeutic approaches aimed at eradicating HIV-1 reservoirs is the “shock and kill” strategy which is based on HIV-1 reactivation in latently-infected cells (“shock” phase) while maintaining antiretroviral therapy (ART) in order to prevent spreading of the infection by the neosynthesized virus. This kind of strategy allows...
Background
People living with HIV (PLWH) have been observed to have twice the risk for atherosclerotic cardiovascular disease (ASCVD) as the general population. Increases in total and low-density lipoprotein cholesterol have been observed in PLWH switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Changes in regimens...
Despite efficient combination of the antiretroviral therapy (cART), which significantly decreased mortality and morbidity of HIV-1 infection, a definitive HIV cure has not been achieved. Hidden HIV-1 in cellular and anatomic reservoirs is the major hurdle toward a functional cure. Microglial cells, the Central Nervous system (CNS) resident macropha...
Introduction
Increased prevalence of low bone mineral density (BMD) and increased fracture incidence are observed in persons living with HIV (PLWH). The trabecular bone score (TBS) is a novel index of bone microarchitecture which improves fracture prediction independent of BMD.
Methods
The HIV UPBEAT study is a single centre, prospective cohort st...
Multivariable model; Predictors of TBS in HIV UPBEAT cohort including bone turnover markers.
Model (i) CTx, (ii) OC and (iii) P1NP (all models are adjusted for the individual bone turnover marker in addition to adjustment for age, gender, ethnicity and BMI). HIV status denotes HIV- positive versus HIV -negative status, TBS—Trabecular bone score C.I...
Unadjusted and adjusted analysis within the HIV positive subgroup exploring associations between HIV-specific factors and lower TBS.
*All variables adjusted for age, gender, Ethnicity, body mass index and current smoking status. Variables which remained significant following these adjustments remained in subsequent models until association was lost...