Publications by authors named "Alagaratnam J"

Intro: Public health restrictions were introduced in the UK in March 2021 in response to the COVID-19 pandemic. The aim of our study was to understand the impact of the disruptions to routine healthcare services among people with HIV during this time and the effect on their engagement with healthcare, social, employment, and relationship networks and mental and physical well-being, to inform advanced planning in the event of future healthcare service disruptions.

Methods: An online survey was conducted, with participants recruited from one HIV clinic and one community organization in England.

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Increasingly, people attending HIV services are requesting long-acting injectable (LAI) antiretroviral treatment (ART). However, without HIV RNA resistance-associated mutation results, individuals are considered unsuitable for LAI ART. We present our experience of sequencing proviral HIV DNA in 30 individuals to inform suitability for LAI ART, of whom 23 were considered suitable.

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  • The study investigates the effects of antiretroviral therapy (ART) interruption on neuro-axonal injury, specifically measuring levels of neurofilament light protein (NfL) in individuals during primary HIV-1 infection.
  • Findings show that NfL decreased after 48 weeks of ART, indicating reduced neuronal injury, and remained stable despite viral rebound after ART interruption.
  • Additionally, baseline NfL levels correlated with higher plasma HIV-1 RNA and older age but showed no significant relationship with inflammation markers like IL-6 or total HIV-1 DNA.
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Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population.

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Background: The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated.

Key Points Of The Guidelines Update: Version 12.0 of the guidelines recommend the same six first-line treatment options for antiretroviral treatment (ART)-naïve adults as versions 11.

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People living with HIV are at increased risk for depression, though the underlying mechanisms for this are unclear. In the general population, depression is associated with peripheral and central inflammation. Given this, and since HIV infection elicits inflammation, we hypothesised that peripheral and central inflammatory biomarkers would at least partly mediate the association between HIV and depressive symptoms.

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  • A study focused on 42 individuals with unclear HIV status found that most were HIV elite controllers, meaning they can suppress the virus without treatment.
  • The research confirmed HIV infection in 30 participants and excluded it in 10, while 2 remained unconfirmed, with elite controllers showing normal immune cell counts.
  • The study highlights the need for more research on different molecular categories within elite controllers, as 95% of the HIV statuses were resolved during the investigation.*
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Objectives: In response to the COVID-19 pandemic, HIV outpatient attendances were restricted from March 2020, resulting in reduced frequency of HIV viral load (VL) monitoring (previously 6-monthly) in clinically stable and virologically suppressed people living with HIV (PLWH). We investigated virological outcomes during this period of reduced monitoring and compared with the previous year, prior to the COVID-19 pandemic.

Methods: People living with HIV with undetectable VL (<200 HIV RNA copies /mL) on antiretroviral therapy (ART) were identified from March 2018 to February 2019.

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  • Researchers tested a new COVID-19 vaccine called LNP-nCoVsaRNA on healthy adults aged 18-75 to see if it was safe and could create an immune response.
  • The study involved giving participants two doses of the vaccine (one smaller and one larger) about 14 weeks apart, and they monitored any side effects and looked for antibodies in their blood.
  • Results showed that most participants developed antibodies against the virus, and the vaccine was generally well-tolerated, meaning it didn't cause serious problems.
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Background: People with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) with good CD4 T-cell counts make effective immune responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are few data on longer term responses and the impact of a booster dose.

Methods: Adults with HIV were enrolled into a single arm open label study.

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Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation.

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People with HIV now have near-normal life expectancies due to the success of effective combination antiretroviral therapy (cART). Following cART initiation, immune recovery occurs, and opportunistic diseases become rare. Despite this, high rates of non-infectious comorbidities persist in treated people with HIV, hypothesized to be related to persistent immuno-activation.

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Cerebrospinal fluid (CSF) neurofilament light protein (NfL) is a marker of central nervous system neuro-axonal injury. A novel, ultra-sensitive assay can determine plasma NfL. In untreated people-with-HIV (PWH), CSF and plasma NfL are strongly correlated.

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Article Synopsis
  • The study aimed to examine the effects of HIV-remission strategies, specifically a "kick-and-kill" approach, on neuro-axonal injury as measured by plasma neurofilament light (NfL) levels in participants of the RIVER trial.
  • Researchers measured plasma NfL, HIV-1 RNA, and HIV-1 DNA in participants who received either standard ART or the additional kick-and-kill regimen; they found no significant differences in NfL levels between the two groups over time.
  • While increased HIV-specific T-cell responses were noted in those receiving the kick-and-kill strategy, these immune responses did not correlate with NfL levels, indicating that this approach may
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Objective: To assess the overall pooled correlation coefficient estimate between cerebrospinal fluid (CSF) and blood neurofilament light (NfL) protein.

Methods: We searched Medline, Embase and Web of Science for published articles, from their inception to 9 July 2019, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies reporting the correlation between CSF and blood NfL in humans were included.

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Background: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV.

Methods: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18-55 years with HIV were enrolled at two HIV clinics in London, UK.

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  • The study aimed to analyze the clinical, lab, and imaging features of people with HIV experiencing cerebrospinal fluid (CSF) HIV RNA escape at clinics in the UK and Italy.
  • A total of 106 individuals were identified, with the majority presenting acute symptoms like cognitive decline, confusion, and headache, particularly in those with higher CSF HIV RNA levels.
  • Findings indicate that cognitive decline is more common in chronic cases, suggesting the need for close monitoring of PWH with CSF HIV RNA escape for specific symptoms based on the timing and severity of their condition.
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Objectives: As people with HIV (PWH) age, the prevalence of frailty increases. Rapid screening tests to identify frailty within HIV outpatient settings are required to identify at-risk individuals. We undertook a service evaluation to assess three short frailty assessments in PWH.

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Background: In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy.

Methods: This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018.

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We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up.

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  • A new analytical method using high-performance liquid chromatography tandem mass spectrometry was developed to accurately measure cenicriviroc (CVC) levels in human plasma and cerebrospinal fluid (CSF).
  • The process included sample preparation with acetonitrile, column separation utilizing a specific gradient, and detection via positive ion mode with selected reaction monitoring.
  • The method proved to be precise and accurate, validating a calibration range for plasma (5 to 1000 ng/mL) and CSF (0.241 to 15.0 ng/mL), with over 90% recovery of CVC from both types of fluids.
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Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people's quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla™) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera™).

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Objectives: The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH).

Methods: PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into 'low' (< 10%), 'intermediate' (10-20%) and 'high' (> 20%) categories for each.

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