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Background INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. Objectives We analysed ART-naive patients who started INSTI-based regimens in 2012–19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. Methods Kaplan–Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. Results Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5–6.7) and 16.2% (95% CI 14.9–17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55–3.04, P 3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55–4.79, P Conclusions This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe.

Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Background: INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. Objectives: We analysed ART-naive patients who started INSTI-based regimens in 2012-19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. Methods: Kaplan-Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. Results: Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5-6.7) and 16.2% (95% CI 14.9-17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55-3.04, P < 0.001] increased the risk of VF, while a pre-treatment CD4 count ≥200 cells/mm3 reduced the risk (aHR 0.52, 95% CI 0.37-0.74, P < 0.001). Predictors of INSTI-DC included use of raltegravir versus dolutegravir (aHR 3.03, 95% CI 2.34-3.92, P < 0.001), use of >3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55-4.79, P < 0.001) and starting ART following availability of dolutegravir (aHR 0.64, 95% CI 0.48-0.83, P = 0.001). Major INSTI mutations indicative of transmitted drug resistance occurred in 2/1114 (0.2%) individuals. Conclusions: This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe. publishersversion published

In the context of the COVID-19 pandemic and overloaded hospitals, a central issue is the need to define reliable and consensual criteria for hospitalization or outpatient management in mild cases of COVID-19. Our aim was to define an easy-to-use clinical rule aiming to help emergency physicians in hospitalization or outpatient management decision-making for patients with suspected or confirmed SARS-CoV-2 infection (the HOME-CoV Rule). The Delphi method was used to reach a consensus of a large panel of 51 experts: emergency physicians, geriatricians, infectious disease specialists, and ethical consultants. A preliminary list of eligible criteria was compiled based on a literature review. Four rounds of anonymized expert consultations were performed. The experts were asked to score each item as relevant, possibly relevant and non-relevant, as major or minor, and to choose the cut-off. They were also able make suggestions and remarks. Eight criteria constituting the HOME-CoV were selected: six correspond to the severity of clinical signs, one to the clinical course (clinically significant worsening within the last 24 hours), and the last corresponds to the association of a severe comorbidity and an inadequate living context. Hospitalization is deemed necessary if a patient meets one or more of the criteria. In the end, 94.4% of the experts agreed with the defined rule. Thanks to the Delphi method, an absolute consensus was obtained of a large panel of experts on the HOME-CoV rule, a decision-making support mechanism for clinicians to target patients with suspected or confirmed COVID-19 requiring hospitalization.Trial registration: NCT04338841

To evaluate the effect of primary resistance and selected polymorphic amino-acid substitutions in HIV reverse transcriptase and protease on the CD4 cell count and viral load set point before the start of antiretroviral treatment.Design:Prospective cohort study.Methods:A total of 6180 individuals with a resistance test prior to starting antiretroviral treatment accessing care in HIV clinics across Europe who had at least one viral load and one CD4 test available were included in the analysis. The impact of amino-acid substitutions variants on viral load and CD4 trends was investigated using linear mixed models. Clusters of mutations were studied using principal component analysis.Results:Overall, the detection of any primary resistance was not associated with either the speed of CD4 cell decline or the viral load set point. However, transmitted nucleoside reverse transcriptase inhibitor and protease inhibitor resistance appeared to be weakly associated with lower viral load set points, as were the polymorphic G16E or Q92K protease mutations. There was some evidence suggesting that these effects varied according to HIV subtype, with the effects of transmitted nucleoside reverse transcriptase inhibitor and protease resistance being particularly marked among individuals with a subtype B virus. A cluster of five polymorphic protease substitutions at position 20, 13, 36, 69 and 89 was associated with less steep CD4 cell declines and lower viral load set points.Conclusion:Although we found little evidence for an association between primary resistance and CD4 speed of decline and viral load set point, the potential role of polymorphic protease (alone or in clusters) and their interplay with HIV subtype needs to be further evaluated. © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Background Estimation of temporal changes in human immunodeficiency virus (HIV) transmission patterns can help to elucidate the impact of preventive strategies and public health policies. Methods Portuguese HIV-1 subtype B and G pol genetic sequences were appended to global reference data sets to identify country-specific transmission clades. Bayesian birth-death models were used to estimate subtype-specific effective reproductive numbers (Re). Discrete trait analysis (DTA) was used to quantify mixing among transmission groups. Results We identified 5 subtype B Portuguese clades (26–79 sequences) and a large monophyletic subtype G Portuguese clade (236 sequences). We estimated that major shifts in HIV-1 transmission occurred around 1999 (95% Bayesian credible interval [BCI], 1998–2000) and 2000 (95% BCI, 1998–2001) for subtypes B and G, respectively. For subtype B, Re dropped from 1.91 (95% BCI, 1.73–2.09) to 0.62 (95% BCI,.52–.72). For subtype G, Re decreased from 1.49 (95% BCI, 1.39–1.59) to 0.72 (95% BCI, .63–.8). The DTA suggests that people who inject drugs (PWID) and heterosexuals were the source of most (>80%) virus lineage transitions for subtypes G and B, respectively. Conclusions The estimated declines in Re coincide with the introduction of highly active antiretroviral therapy and the scale-up of harm reduction for PWID. Inferred transmission events across transmission groups emphasize the importance of prevention efforts for bridging populations., The Journal of Infectious Diseases, 220 (2), ISSN:0022-1899, ISSN:1537-6613

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings. © 2018 The Author(s).

HIV-1 non-B subtype infections have been observed in Belgium since the 1980s. However, subtype B predominates amongst men having sex with men (MSM), whereas other subtypes are mainly associated with sub-Saharan African migrants and heterosexual risk behavior. In the last decade, subtype F1 diagnoses have increased substantially in Belgium, representing 9% of newly diagnosed and therapy-naïve HIV-1 patients linked to care in 2014. In the present study, the Belgian subtype F1 epidemic has been characterized within a global context, where F1 is responsible for