for the DRIVE-SHIFT Study Group Background: Doravirine is a novel, nonnucleoside reverse transcriptase inhibitor with demonstrated efficacy in treatmentnaive adults with HIV-1. Methods: In this open-label, active-controlled, noninferiority trial, adults with HIV-1 virologically suppressed for $6 months on 2 nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor, boosted elvitegravir, or a non-nucleoside reverse transcriptase inhibitor were randomized (2:1) to switch to once-daily, singletablet doravirine 100 mg with lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) or to continue their current therapy (Baseline Regimen) for 24 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA ,50 copies/mL (defined by the FDA Snapshot approach), with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24 and a secondary comparison between the groups at week 24 (noninferiority margin, 28%). Results: Six hundred seventy participants (447 DOR/3TC/TDF, 223 Baseline Regimen) were treated and included in the analyses. At week 24, 93.7% on DOR/3TC/TDF vs 94.6% on Baseline Regimen had HIV-1 RNA ,50 copies/mL [difference 20.9 (24.7 to 3.0)]. At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA ,50 copies/mL, demonstrating noninferiority vs Baseline Regimen at week 24 [difference 23.8 (27.9 to 0.3)]. In participants on ritonavirboosted protease inhibitor at entry, mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/ 3TC/TDF vs Baseline Regimen (P , 0.0001). Adverse events occurred in 68.9% on DOR/3TC/TDF and 52.5% on Baseline Regimen by week 24, leading to treatment discontinuation in 2.5% and 0.4%, respectively. Conclusions: Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy.

Supplemental Digital Content is Available in the Text.

BackgroundDoravirine is a novel, non-nucleoside reverse-transcriptase inhibitor (NNRTI) that has demonstrated efficacy in two Phase 3 trials in treatment-naïve adults with HIV-1.MethodsThis open-label, active-controlled, noninferiority (NI) trial evaluated a once-daily single-tablet regimen of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) vs. continuation of current therapy in adults with HIV-1 virologically suppressed for ≥6 months on a stable regimen of two NRTIs plus a boosted protease inhibitor (PI), boosted elvitegravir, or NNRTI. Participants with screening HIV-1 RNA <40 copies/mL, no history of virologic failure on any regimen, and no resistance to DOR/3TC/TDF were randomized (2:1) to start DOR/3TC/TDF on Day 1 (immediate switch group, ISG) or after 24 weeks (delayed switch group, DSG). The primary endpoint was the proportion (%) of participants with HIV-1 RNA <50 copies/mL (FDA snapshot approach), with the primary comparison between ISG at Week 48 and DSG at Week 24 and a secondary comparison between the groups at Week 24; the NI margin was -8%. The % of participants with HIV-1 RNA ≥50 copies/mL was also analyzed (FDA snapshot approach; NI margin 4%).ResultsA total of 670 participants (447 ISG, 223 DSG) were treated and included in the analyses; 84.5% were male, 76.4% were white, and mean age was 43.3 years. At Week 24, 93.7% (419/447) of ISG vs. 94.6% (211/223) of DSG had HIV-1 RNA <50 copies/mL (difference −0.9% [−4.7, 3.0]), and 1.8% of each group had HIV-1 RNA ≥50 copies/mL. At Week 48, 90.8% (406/447) of ISG maintained HIV-1 RNA <50 copies/mL (vs. 94.6% of DSG at Week 24; difference −3.8%, 95% CI [−7.9%, 0.3%]), and 1.6% of ISG had HIV-1 RNA ≥50 copies/mL. In the ritonavir-boosted PI stratum, mean changes in fasting LDL-C and non-HDL-C at Week 24 were significantly lower (P < 0.0001) in ISG vs. DSG (table). Rates of any AE and of drug-related AEs at Week 24 were higher in ISG vs. DSG. AEs were mild in most ISG participants (64% of those with any AE; 80% of those with drug-related AEs).ConclusionA once-daily single-tablet regimen of DOR/3TC/TDF demonstrated non-inferior efficacy and acceptable safety compared with continuing therapy, and is an option for maintaining viral suppression in patients considering a change in therapy.Disclosures P. Kumar, Merck, Pfizer, Janssen,: Grant Investigator and Shareholder, Research grant. GSK, Gilead, Teratechnologies, TaiMed,: Grant Investigator, Scientific Advisor and Shareholder, Consulting fee and Research grant. J. M. Molina, Merck GIlead ViiV Janssen Teva: Ad Board and Speaker’s Bureau, Consulting fee. Gilead Sciences: Grant Investigator, Research support. G. Rizzardini, ViiV, Gilead Science, MSD, Angelini, and Abbvie: Board Member and Speaker’s Bureau, Speaker honorarium. Gliead, ViiV, and MSD: Research Contractor, Research grant. P. Cahn, Abbvie: Grant, Research grant. Merck: Grant, Advisory Board. ViiV Healthcare: Grant, Advisory Board. M. Bickel, Merck & Co., Inc.: Research Contractor, Research grant. ...

No abstract

Introduction The COVID-19 pandemic had a major impact on the mental health of workers, in particular healthcare professionals. The social isolation used as a mitigation measure against infection contributed to a reduction in sleep quality, and an increase in depressive symptoms, anxiety, and burnout. Objectives The aims of this study are to assess the impact of isolation and quarantine on the mental health and sleep quality of healthcare professionals in a Portuguese Oncology Institute. Material and Methods An online form was distributed to all healthcare professionals who were in isolation or quarantine during the year 2020 in the IPO-Porto, consisting of three instruments- sociodemographic survey, Mental Health Inventory (MHI) and Basic Insomnia and Sleep Quality Scale (BaSIQS). Data were collected in two moments, from July 25 to December 25, 2020, and in December 2021. Results A total of 359 healthcare professionals were identified (151 by isolation and 208 by quarantine). In the 2020 analysis, 115 responses were obtained (54 by isolation and 61 by quarantine), resulting in a response rate of 32.0%. In the 2021 analysis, 76 responses were obtained with a response rate of 21.1%. Regarding the healthcare professionals in our study, the dimensions that make up the psychological stress of the MHI, show an improvement after the first year of the pandemic, as well as an improvement in the mean total MHI value from 2020 to 2021. Sleep quality (assessed by the BaSIQS) is in the poor-to-intermediate category in the 2020 assessment. Although the 2021 assessment shows a slightly better mean, there is no statistically significant difference between the two. In this sample of health professionals, mental health and sleep quality correlated for the instruments used. Discussion and conclusions Insomnia and sleep quality are a modifiable factor of mental health, with an impact on the quality of life and productivity of healthcare professionals. Social isolation as a disruptor of sleep, daily routine and healthy interaction in work teams may be a factor that aggravates psychological distress. The investment in mental health promotion programs, as well as the coordination of multidisciplinary teams composed of Psychology, Medicine and Occupational Nursing are essential in the monitoring and surveillance of these workers’ health. KEY WORDS: Mental Health, Healthcare Professionals, Occupational Psychology, COVID-19, Occupational Medicine, Occupational Health.