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      Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice: a multicentre cohort study

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          Abstract

          Background The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014–2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads.

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          A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results

          Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1023-4) contains supplementary material, which is available to authorized users.
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            [The Cohort of the Spanish HIV Research Network (CoRIS) and its associated biobank; organizational issues, main findings and losses to follow-up].

            This article describes the development of the Cohort of the Spanish Research Network (CoRIS), its methodological and organizational aspects, the demographic and clinical characteristics of the subjects enrolled and quantifies the losses to follow-up and associated factors. Multicentre cohort of HIV-positive naïve subjects recruited in 28 sites of Spain from 2004-onwards. Missing and inconsistent data were submitted to internal quality controls and the datasets were externally audited. Multiple logistic regression models were used. As of October 2009, 5,514 subjects had been recruited, representing 11,708 person-years with a median follow-up time of 1.81 years. Most are men (78.8%), infected by sexual transmission (46.1% men who have sex with men and 35.2% heterosexual persons) and Spanish (69.7%). During follow-up 64.5% have started Antiretroviral Therapy (ART) and 201 deaths have occurred. New HIV diagnoses accounted for 80.7% of the sample. Some 52% of subjects had at least one baseline sample in the BioBank while naïve to ART. Losses to follow-up (18.9%) were more frequent in younger people, in injecting drug users, in persons of non-Spanish origin, in persons with primary or lower educational level, and in those with a CD4 count over 350 cells/mm(3) at time of recruitment. The implementation of CoRIS has been successful; the cohort has wide representation at national level, is actively recruiting new members and blood samples, and has excellent data quality. Losses to follow-up are of similar magnitude to other cohort studies, as are the factors associated with them. Copyright © 2011 Elsevier España, S.L. All rights reserved.
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              A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults

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                Author and article information

                Contributors
                inessuarez@hotmail.com
                Journal
                AIDS Res Ther
                AIDS Res Ther
                AIDS Research and Therapy
                BioMed Central (London )
                1742-6405
                20 July 2020
                20 July 2020
                2020
                : 17
                : 45
                Affiliations
                [1 ]GRID grid.414758.b, ISNI 0000 0004 1759 6533, Department of Internal Medicine, Infectious Diseases Group, , Hospital Universitario Infanta Sofía, ; Paseo de Europa, 34. San Sebastián de los Reyes, 28702 Madrid, Spain
                [2 ]FIIB HUIS HHEN, Madrid, Spain
                [3 ]GRID grid.441415.1, Universidad Europea, ; Madrid, Spain
                [4 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, ; Madrid, Spain
                [5 ]GRID grid.411347.4, ISNI 0000 0000 9248 5770, Hospital Universitario Ramón y Cajal, ; Madrid, Spain
                [6 ]GRID grid.428313.f, ISNI 0000 0000 9238 6887, Corporació Sanitària Parc Taulí, ; Barcelona, Spain
                [7 ]GRID grid.411086.a, ISNI 0000 0000 8875 8879, Hospital General Universitario de Alicante, ; Alicante, Spain
                [8 ]GRID grid.411109.c, ISNI 0000 0000 9542 1158, Hospital Virgen del Rocío, ; Sevilla, Spain
                [9 ]GRID grid.460738.e, Hospital San Pedro Centro de Investigación Biomédica de La Rioja (CIBIR), ; Logroño, La Rioja Spain
                [10 ]GRID grid.419651.e, Hospital Universitario Fundación Jiménez Díaz, ; Madrid, Spain
                [11 ]Hospital de la Marina Baixa, La Vila Joiosa, Spain
                [12 ]GRID grid.413358.8, ISNI 0000 0004 1767 5987, Hospital San Agustín, ; Avilés, Spain
                Author information
                http://orcid.org/0000-0002-7016-716X
                Article
                302
                10.1186/s12981-020-00302-2
                7372769
                32690099
                b61a118d-b71d-46ae-9ea8-4edb361e1098
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 14 January 2020
                : 13 July 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: RD06/006, RD12/0017/0018
                Award ID: RD16/0002/0006
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Infectious disease & Microbiology
                hiv infection,highly active antiretroviral therapy,cohort studies,darunavir

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