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Two elvitegravir/cobicistat‐based therapies combined with emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) or emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) are currently available for HIV patients. This study evaluated the modifications in the lipid profile of patients who received these treatments in the last three years at our institution. A retrospective observational study in HIV‐infected patients who received EVG/c/FTC/TDF or EVG/c/FTC/TAF from January 2015 to January 2018 at a reference hospital in northwestern Spain was carried out. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed using SPSS software. A total of 384 EVG/c‐based therapies were initiated during the study period, 151 EVG/c/FTC/TDF and 233 EVG/c/FTC/TAF. A significantly negative influence in all the lipid profile parameters in experienced patients and total cholesterol (TC), and LDL‐C in naïve patients were observed after 48 weeks of treatment with EVG/c/FTC/TAF, while these parameters remained stable in the EVG/c/FTC/TDF group. During follow‐up, a greater proportion of patients had lipid levels above the normal range (63.1% TC, 56.2% LDL‐C) and new lipid‐modifying drugs were prescribed (11.9%) in the EVG/c/FTC/TAF group. The number of cardiovascular risk factors (OR 1.66 [95% CI 1.01‐2.72]; P = 0.043) was recognised as an independent predictor of lipid‐lowering prescription for patients treated with both EVG/c/FTC/TDF and EVG/c/FTC/TAF. For patients treated with EVG/c/FTC/TAF, the mean total cholesterol to HDL ratio in the first 48 weeks of the study treatment was associated with a higher likelihood of lipid‐lowering prescription in multivariate analysis (OR 1.6 [95% CI 1.12‐2.52]; P = 0.011). Significant changes in lipid profile have been observed in patients who have received EVG/c/FTC/TAF. It was necessary to prescribe almost twice the number of lipid‐lowering drugs to patients who received EVG/c/FTC/TAF (11.9%) vs EVG/c/FTC/TDF (4.7%). [ABSTRACT FROM AUTHOR]

Introduction: Linezolid is a broadly used antibiotic to treat complicated infections caused by gram-positive bacteria. Therapeutic drug monitoring of linezolid concentrations is recommended to maximise its efficacy and safety, mainly haematological toxicity. Different pharmacokinetic/pharmacodynamic targets have been proposed to improve linezolid exposure: the ratio of the area under the concentration-time curve during a 24-hour period to minimum inhibitory concentration (MIC) between 80 and 120; percentage of time that the drug concentration remains above the MIC during a dosing interval greater than 85% and the trough concentration between 2 and 7 mg/L. This clinical trial aims to evaluate the safety, efficacy and the clinical and economic utility of personalised dosing of linezolid using Bayesian forecasting methods to attain pharmacokinetic/pharmacodynamic targets, known as model-informed precision dosing., Methods and Analysis: This is a pragmatic, multicentre, randomised, parallel, controlled, phase IV and low intervention trial. Participants will be randomly assigned 1:1 to each group (n=346 per group). Control group will receive the standard dose of linezolid. Intervention group will receive personalised dosage of linezolid based on pharmacokinetic-pharmacodynamic adjustments. The primary outcome will be the incidence of thrombocytopenia in both groups., Ethics and Dissemination: This protocol was approved by the Ethical Committee of the Investigation with Medicines of Galicia (code 2022/140) and authorised by the Spanish Agency for Medicines and Medical Devices. The trial is implemented in accordance with the Declaration of Helsinki and the international ethical and scientific quality standard, the Good Clinical Practice. The results will be published in peer-reviewed journals., Trial Registration Number: EudraCT registration code: 2022-000144-30., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF., Methods: Multicenter prospective cohort study in the Spanish CoRIS cohort. We included virologically suppressed adults with human immunodeficiency virus (HIV) receiving TDF for more than 12 months who either switched to TAF or maintained TDF, with no changes in the core agent. Participants were matched by propensity score. We fitted generalized equation models to assess changes in weight, blood lipids, and hepatic steatosis index, and to compare the incidence of diabetes, hypertension, and lipid-lowering drug use after 144 weeks., Results: In total, 1446 participants were matched in each group. Median age was 38 years, 85% were male, mean weight at baseline was 73 kg. Participants who switched to TAF had a mean weight increase of +0.5 kg at 144 weeks over those who maintained TDF, with no difference in the occurrence of overweight or obesity. Individuals who switched to TAF had a significant increase in total cholesterol (+7.9 mg/dL) and triglycerides (+11.2 mg/dL), with no differences in the total cholesterol-high-density lipoprotein (HDL) ratio. However, no increased incidence of diabetes, hypertension, or lipid-lowering drug use was observed after the follow-up period., Conclusions: Switching from TDF to TAF is associated with modest weight gain and increases in total cholesterol and triglycerides, without an impact on the incidence of obesity or metabolic-related clinical events, in this Spanish cohort with a majority White male population., Competing Interests: Potential conflicts of interest. J. M.-S. reports personal fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and Merck Sharp & Dohme (MSD) and non-financial support from ViiV Healthcare, Jannsen Cilag, and Gilead Sciences, including support for attending meetings and/or travel, outside the submitted work. A. M. d. C. reports personal fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD and non-financial support from Jannsen Cilag and Gilead Sciences, including support for attending meetings and/or travel. S. M. reports grants, personal fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, participation on a Data Safety Monitoring Board or Advisory Board, support for attending meetings and/or travel, and non-financial support from ViiV Healthcare; personal fees, grants or contracts, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, participation on a Data Safety Monitoring Board or Advisory Board, support for attending meetings and/or travel and non-financial support from Janssen; grants, personal fees, participation on a Data Safety Monitoring Board or Advisory Board and non-financial support including support for attending meetings and/or travel from MSD; grants, personal fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, support for attending meetings and/or travel, participation on a Data Safety Monitoring Board or Advisory Board and non-financial support from Gilead, outside the submitted work, and grants or contracts from the Instituto de Salud Carlos III. S. S.-V. reports grants or contracts from Instituto de Salud Carlos III (ICI20/00058, COV20/00349, PI21/00041) and from Merck (IISP 60257, IISP 59181); personal fees from Gilead Sciences; as well as non-financial support from ViiV Healthcare, Merck and Gilead Sciences; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Gilead Sciences; support for attending meetings and/or travel from ViiV and Gilead; patents planned, issued or pending (EP19382159, “Anal bacterial biomarkers for the diagnosis of anal precancerous lesions” and EP21382486, “Biomarker and methods to predict susceptibility to SARS-CoV-2 and COVID19 severity”), and research grants from MSD, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)