Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT).

Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy.

Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART.

Depression is associated with poor self-reported adherence to antiretroviral therapy among people living with HIV attending an HIV clinic in the UK: results from a cross-sectional study.

Contemporary evidence is needed to assess whether the prevalence of depression remains high among people living with HIV in the United Kingdom despite recent efforts to improve patients' mental health, and if depression is negatively associated with individuals' adherence to antiretroviral therapy. In a secondary analysis of a cross-sectional clinic-based survey of alcohol consumption and associated health behaviour among people living with HIV in London, of the 221 respondents, 106 (48%) had poor self-reported adherence to antiretroviral therapy (CASE Index) and 69 (31%) screened positive for depression (PHQ-9). Poor self-reported adherence to ART was 72% higher among participants who screened positive for depression in comparison with participants who screened negative.

Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial.

The aim of this study is to identify the factors associated with peripheral neuropathy and to explore neurofilament light chain (NfL) as a biomarker for peripheral neuropathy (PN) in effectively virologically suppressed adults living with HIV. All protease inhibitor monotherapy versus ongoing triple therapy in the long-term management of HIV infection (PIVOT) trial participants with data on PN at baseline were included in the study. NfL plasma levels (pNfL) were measured in a sub-set of participants.

How surgical Trainee Research Collaboratives achieve success: a mixed methods study to develop trainee engagement strategies.

Objectives: This study aimed to understand the role of surgical Trainee Research Collaboratives (TRCs) in conducting randomised controlled trials and identify strategies to enhance trainee engagement in trials.

Design: This is a mixed methods study. We used observation of TRC meetings, semi-structured interviews and an online survey to explore trainees' motivations for engagement in trials and TRCs, including barriers and facilitators.

Bone turnover change after randomized switch from tenofovir disoproxil to tenofovir alafenamide fumarate in men with HIV.

Objective: Bone loss in people with HIV (PWH) is poorly understood. Switching tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) has yielded bone mineral density (BMD) increases. PETRAM (NCT#:03405012) investigated whether BMD and bone turnover changes correlate.

Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV-negative controls: A cross-sectional study nested within the POPPY cohort.

Background: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV.

Methods: Older (>50 years) and younger (<50 years) people with HIV and older HIV-negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Background: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

Methods: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA.

Derivation of a Protein Risk Score for Cardiovascular Disease Among a Multiracial and Multiethnic HIV+ Cohort.

Background Cardiovascular disease risk prediction models underestimate CVD risk in people living with HIV (PLWH). Our goal is to derive a risk score based on protein biomarkers that could be used to predict CVD in PLWH. Methods and Results In a matched case-control study, we analyzed normalized protein expression data for participants enrolled in 1 of 4 trials conducted by INSIGHT (International Network for Strategic Initiatives in Global HIV Trials).

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

Background: For people with HIV and CD4 counts >500 cells/mm, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4 counts are <350 cells/mm. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.

Methods: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4 counts .

Learning and memory function in young people with and without perinatal HIV in England.

Learning and memory are important for successful education and career progression. We assess these functions in young people (YP) with perinatal HIV (PHIV) (with or without a previous AIDS-defining illness) and a comparable group of HIV-negative YP. 234 PHIV and 68 HIV-negative YP completed 9 tests; 5 National Institutes of Health (NIH) Toolbox tests (2 executive function, 1 speed of information processing, 2 memory); 2 Hopkins Verbal Learning Test Revised (HVLT-R) (learning (L), delayed recall (R)), and 2 verbal application measures.

Alcohol, smoking, recreational drug use and association with virological outcomes among people living with HIV: cross-sectional and longitudinal analyses.

Objectives: There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non-adherence, viral non-suppression and subsequent viral rebound in PLWH.

Methods: The Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study recruited PLWH attending eight outpatient clinics in England between February 2011 and December 2012.

SARS-CoV-2 inhibition using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray.

There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19.

Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity.

Background: Understanding the genetic interplay between human hosts and infectious pathogens is crucial for how we interpret virulence factors. Here, we tested for associations between HIV and host genetics, and interactive genetic effects on viral load (VL) in HIV-positive antiretroviral treatment-naive clinical trial participants.

Methods: HIV genomes were sequenced and the encoded amino acid (AA) variants were associated with VL, human single nucleotide polymorphisms (SNPs), and imputed HLA alleles using generalized linear models with Bonferroni correction.

Network meta-analysis of post-exposure prophylaxis randomized clinical trials.

Objectives: We performed a network meta-analysis of PEP randomized clinical trials to evaluate the best regimen.

Methods: After MEDLINE/Pubmed search, studies were included if: (1) were randomized, (2) comparing at least 2 PEP three-drug regimens and, (3) reported completion rates or discontinuation at 28 days. Five studies with 1105 PEP initiations were included and compared ritonavir-boosted lopinavir (LPV/r) vs.

Factors Associated With Nonadherence to Antiretroviral Therapy Among Young People Living With Perinatally Acquired HIV in England.

Young people living with perinatally acquired HIV may be at risk of poor adherence to antiretroviral therapy; identification of predictors, using a conceptual framework approach proposed previously by others, is important to identify those at higher risk. In 261 young people with perinatally acquired HIV in England, 70 (27%) reported 3-day nonadherence, 82 (31%) last month nonadherence, and 106 (41%) nonadherence on either measure. Of those reporting nonadherence on both measures, 52% (23/44) had viral load of <50 copies/ml, compared with 88% (127/145) of those reported being fully adherent.

Genital secretion HIV RNA shedding in HIV-positive patients on ritonavir-boosted protease inhibitor monotherapy or standard combination ART: a cross-sectional sub-study from the PIVOT Trial.

Background: Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono).

Methods: We measured HIV RNA and PI drug concentrations in samples of semen, cervico-vaginal and rectal mucosa secretions, and plasma in patients after 48-96 weeks on PI-mono or standard triple therapy.

Results: A total of 85 participants were recruited.

Reversible effect on lipids by switching from tenofovir disoproxil fumarate to tenofovir alafenamide and back.

Objective: The aim of the current study is to assess the effect of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on lipids in patients switching from TDF to TAF and back.

Methods: Retrospective data collection on patients who were initially switched from TDF to TAF and switched back to TDF after generics of TDF became available.

Results: In total, 385 patients were included.

Risky Alcohol Consumption and Associated Health Behaviour Among HIV-Positive and HIV-Negative Patients in a UK Sexual Health and HIV Clinic: A Cross-Sectional Questionnaire Study.

Alcohol misuse has been associated with negative consequences among HIV-positive patients. Data on real prevalence of risky alcohol consumption among the HIV-positive population in the UK are lacking. A cross-sectional questionnaire study using standardised validated instruments among HIV-positive (n = 227) and HIV-negative (n = 69) patients was performed.

Benefit of Early versus Deferred Antiretroviral Therapy on Progression of Liver Fibrosis among People with HIV in the START Randomized Trial.

The role of antiretroviral therapy (ART) in reducing or contributing to liver fibrosis in persons with human immunodeficiency virus (HIV) is unclear. We evaluated participants in the Strategic Timing of AntiRetroviral Treatment (START) trial for liver fibrosis using the AST to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4), and assessed for a benefit of early versus delayed ART on liver fibrosis progression. ART-naïve persons with high CD4 counts (>500 cells/µL) from 222 clinical sites in 35 countries were randomized to receive ART either at study enrollment (immediate treatment arm) or when their CD4 count fell below 350 cells/µL (deferred treatment arm).

Brain Perfusion, Regional Volumes, and Cognitive Function in Human Immunodeficiency Virus-positive Patients Treated With Protease Inhibitor Monotherapy.

Background: Protease inhibitor monotherapy (PIM) for human immunodeficiency virus (HIV) may exert suboptimal viral control in the central nervous system. We determined whether cerebral blood flow (CBF) and regional brain volumes were associated with PIM, and whether specific cognitive domains were associated with imaging biomarkers.

Methods: Cognitive assessments and brain magnetic resonance imaging were performed after the final visit of a randomized HIV-treatment strategy trial.

Anxiety and depression symptoms in young people with perinatally acquired HIV and HIV affected young people in England.

Adolescents with perinatal HIV (PHIV) may be at higher risk of anxiety and depression than HIV negative young people. We investigated prevalence of anxiety and depression symptoms in 283 PHIV and 96 HIV-affected (HIV-negative) young people in England recruited into the Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort. We used Hospital Anxiety and Depression Scale (HADS) scores and linear regression investigated predictors of higher (worse) scores.

Next generation sequencing of HIV-1 protease in the PIVOT trial of protease inhibitor monotherapy.

Background: The PIVOT trial examined whether patients with suppressed viral load on combination antiretroviral therapy could be safely switched long-term to ritonavir-boosted protease inhibitor (PI) monotherapy. The main trial publication reported that only one of 296 patients allocated to PI monotherapy experienced a loss of drug options due to protease mutations (identified by local Sanger sequencing resistance tests) likely selected by study drug.

Objectives: To assess if we had missed low frequency mutations, using a more sensitive methodology.

No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts.

Objective: To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/μl.

Design: Randomized trial.

Methods: The START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/μl.