Publications by authors named "Giuliano Rizzardini"

181 Publications

How to Manage COVID-19 Vaccination in Immune-Mediated Inflammatory Diseases: An Expert Opinion by IMIDs Study Group.

Front Immunol 2021;12:656362. Epub 2021 Apr 15.

Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences (DIBIC) L. Sacco, Università degli Studi di Milano, Milan, Italy.

Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy.
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http://dx.doi.org/10.3389/fimmu.2021.656362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082137PMC
April 2021

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial.

Infect Dis Ther 2021 Mar 9. Epub 2021 Mar 9.

Gilead Sciences, Foster City, CA, USA.

Introduction: We report the 48-week results of an ongoing study to assess the efficacy and safety of switching older people with HIV to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

Methods: This was a 96-week, phase 3b, open-label, single-arm study (GS-US-380-4449; NCT03405935). Virologically suppressed individuals aged ≥ 65 years receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen were switched to B/F/TAF. Primary endpoint was the percentage of participants with HIV-1 RNA < 50 copies/ml at week 24.

Results: Eighty-six participants (median age 69 [range 65-80] years; 87% male; 95% white) were enrolled and treated in five European countries. Rates of virologic suppression were 97.7% at week 24 and 90.7% at week 48; none had HIV-1 RNA ≥ 50 copies/ml, and 100% had virologic suppression by missing = excluded analysis at both time points. No treatment-emergent resistance was observed. There were no grade 3-4 study drug-related adverse events (AEs) or study drug-related serious AEs or deaths. Three AEs led to premature discontinuation; one (moderate abdominal discomfort) was attributed to the study drug by the investigator. At week 48, median changes from baseline in weight and estimated glomerular filtration rate were + 0.1 kg (interquartile range [IQR] - 1.0, 2.3) and - 6.0 ml/min (IQR - 10.2, 0.0), respectively. There were no clinically relevant changes from baseline to week 48 in fasting lipid parameters. Treatment satisfaction improved, and health-related quality of life was maintained from baseline through week 48. Median adherence to the study drug was 98.6% (IQR 96.0, 100).

Conclusions: Switching to B/F/TAF was effective and well tolerated through 48 weeks in virologically suppressed adults aged ≥ 65 years.

Trial Registration: ClinicalTrials.gov identifier, NCT03405935.
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http://dx.doi.org/10.1007/s40121-021-00419-5DOI Listing
March 2021

Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial.

J Acquir Immune Defic Syndr 2021 Feb 17. Epub 2021 Feb 17.

Medstar Georgetown University Hospital, Div. of Infectious Diseases and Travel Medicine, Washington DC, USA Royal Free Hospital, Department of HIV Medicine, London UK Saint-Louis and Lariboisière Hospitals, APHP, University of Paris, INSERM U944, Paris, France ASST Fatebenefratelli Sacco Hospital, Department of Infectious Diseases, Milan, Italy Fundación Huésped and Buenos Aires University, Buenos Aires, Argentina Infektiologikum, Centre for Infectious Diseases, Frankfurt, Germany; Merck & Co., Inc., Kenilworth, NJ USA.

Background: In the primary analysis of the DRIVE-SHIFT trial, switching to doravirine/lamivudine/ tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained suppression of HIV-1 through Week 48. Here we present long-term efficacy and safety outcomes through Week 144 of the DRIVE-SHIFT trial.

Methods: This phase 3, randomized, open-label trial evaluated switching from a stable antiretroviral regimen to once-daily DOR/3TC/TDF in adults with HIV-1 suppressed for ≥6 months and no previous virologic failure. Participants switched at Day 1 (immediate-switch group [ISG]; n=447) or Week 24 (delayed-switch group [DSG]; n=209). Nine ISG participants who completed Week 48 but did not enter Extension-1 were excluded from Week 144 efficacy analyses.

Results: At Week 144, HIV-1 RNA <50 copies/mL was maintained in 80.1% of the ISG (351/438) and 83.7% of the DSG (175/209), while 2.7% (12/438) and 4.8% (10/209), respectively, had HIV-1 RNA ≥50 copies/mL (FDA Snapshot). Protocol-defined virologic failure after switch occurred in 2.1% of ISG (9/438) and 3.3% of DSG (7/209); no viral resistance to doravirine was detected in four participants with samples available. Reductions in fasting lipids were observed at 24 weeks post-switch and maintained through Week 144. Mean weight change from switch to Week 144 was +1.4 kg for ISG and +1.2 kg for DSG. The most common adverse events were nasopharyngitis (16.2%), headache (12.3%) and diarrhea (9.1%). Overall, 4.1% discontinued due to adverse events, and no deaths occurred.

Conclusions: These results confirm that switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in adults considering a change in therapy.

Registration: ClinicalTrials.gov NCT02397096.
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http://dx.doi.org/10.1097/QAI.0000000000002642DOI Listing
February 2021

Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.

Dig Liver Dis 2021 03 26;53(3):263-270. Epub 2020 Dec 26.

Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Biomedical and Clinical Sciences "L.Sacco" University of Milan, Italy.

Background: It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19.

Objectives: This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders.

Methods: This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed.

Results: 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17).

Conclusion: IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.
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http://dx.doi.org/10.1016/j.dld.2020.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762705PMC
March 2021

Consumption of antibiotics at an Italian university hospital during the early months of the COVID-19 pandemic: Were all antibiotic prescriptions appropriate?

Pharmacol Res 2021 02 24;164:105403. Epub 2020 Dec 24.

Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy; Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.

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http://dx.doi.org/10.1016/j.phrs.2020.105403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836543PMC
February 2021

Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study.

Lancet 2021 12 9;396(10267):1994-2005. Epub 2020 Dec 9.

ViiV Healthcare, Research Triangle Park, NC, USA.

Background: Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing.

Methods: ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing.

Findings: Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34-50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI -0·6-2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred.

Interpretation: The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1.

Funding: ViiV Healthcare and Janssen.
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http://dx.doi.org/10.1016/S0140-6736(20)32666-0DOI Listing
December 2021

HTA and HIV: The Case of Dual NRTI Backbones in the Italian Setting.

Int J Environ Res Public Health 2020 12 3;17(23). Epub 2020 Dec 3.

Centre on Health Economics, Social and Health Care Management, LIUC Business School, LIUC-Università Cattaneo, 21053 Castellanza, Italy.

The aim of this study is to analyze the potential advantages of emtricitabine/tenofovir alafenamide (FTC/TAF) introduction, creating evidence-based information to orient strategies to reduce costs, thus preserving effectiveness and appropriateness. An Health Technology Assessment (HTA) was implemented in the years 2017-2018 comparing the dual backbones available in the Italian market: FTC/TAF, FTC/TDF (tenofovir disoproxil fumarate/emtricitabine) and ABC/3TC (abacavir/lamivudine). From an efficacy point of view, FTC/TAF ensured a higher percentage of virologic control and a better safety impact than FTC/TDF (improving the renal and bone safety profile, as well as the lipid picture). From an economic point of view, the results revealed a 4% cost saving for the Italian National Healthcare Service NHS with FTC/TAF introduction compared with the baseline scenario. Qualitative perceptions' results showed that FTC/TAF would decrease the burden of adverse events management, increasing the accessibility of patients to healthcare providers (FTC/TAF: 0.95, FTC/TDF: 0.10, ABC/3TC: 0.28; -value: 0.016) and social costs (FTC/TDF: -0.23, FTC/TAF: 1.04, ABC/3TC: 0.23; -value < 0.001), improving patient quality of life (FTC/TDF: 0.31, FTC/TAF: 1.85, ABC/3TC: 0.38; -value < 0.001). Healthcare services may consider the evidence provided by the present study as an opportunity to include HIV patients in a more adequate antiretroviral treatment arm, guaranteeing a personalized clinical pathway, thus becoming more efficient and effective over time.
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http://dx.doi.org/10.3390/ijerph17239010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729444PMC
December 2020

A case of extremely prolonged viral shedding: Could cell cultures be a diagnostic tool to drive COVID-19 patient discharge?

Int J Infect Dis 2021 Mar 20;104:631-633. Epub 2020 Nov 20.

Laboratory of Clinical Microbiology, Virology and Bioemergencies, ASST Fatebenefratelli Sacco, Milan, Italy.

This study addressed the case of a patient with prolonged COVID-19 viral shedding, reported by Real-Time PCR, until 71 days from symptom onset. However, viral culture received negative results after 30 days from symptom onset. Therefore, viral culture may be a worthwhile test for patients requiring discharge, in particular for those presenting prolonged viral shedding.
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http://dx.doi.org/10.1016/j.ijid.2020.11.161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679112PMC
March 2021

Chest X-ray findings in a large cohort of 1117 patients with SARS-CoV-2 infection: a multicenter study during COVID-19 outbreak in Italy.

Intern Emerg Med 2020 Nov 20. Epub 2020 Nov 20.

CERBA HealthCare Italia, Cologno Monzese, Monza Brianza, Italy.

To describe radiographic key patterns on Chest X-ray (CXR) in patients with SARS-CoV-2 infection, assessing the prevalence of radiographic signs of interstitial pneumonia. To evaluate pattern variation between a baseline and a follow-up CXR. 1117 patients tested positive for SARS-CoV-2 infection were retrospectively enrolled from four centers in Lombardy region. All patients underwent a CXR at presentation. Follow-up CXR was performed when clinically indicated. Two radiologists in each center reviewed images and classified them as suggestive or not for interstitial pneumonia, recording the presence of ground-glass opacity (GGO), reticular pattern or consolidation and their distribution. Pearson's χ test for categorical variables and McNemar test (χ for paired data) were performed. Patients mean age 63.3 years, 767 were males (65.5%). The main result is the large proportion of positive CXR in COVID-19 patients. Baseline CXR was positive in 940 patients (80.3%), with significant differences in age and sex distribution between patients with positive and negative CXR. 382 patients underwent a follow-up CXR. The most frequent pattern on baseline CXR was the GGO (66.1%), on follow-up was consolidation (53.4%). The most common distributions were peripheral and middle-lower lung zone. We described key-patterns and their distribution on CXR in a large cohort of COVID-19 patients: GGO was the most frequent finding on baseline CXR, while we found an increase in the proportion of lung consolidation on follow-up CXR. CXR proved to be a reliable tool in our cohort obtaining positive results in 80.3% of the baseline cases.
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http://dx.doi.org/10.1007/s11739-020-02561-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677441PMC
November 2020

Hepatitis B and HIV coinfection in Northern Uganda: Is a decline in HBV prevalence on the horizon?

PLoS One 2020 18;15(11):e0242278. Epub 2020 Nov 18.

Infectious Disease Unit, L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.

Background: The available data concerning hepatitis B virus (HBV) infection in Uganda are limited, particularly in the case of people living with HIV/AIDS (PLWH). HBV is not routinely tested when starting antiretroviral therapy (ART). We aimed to determine the prevalence, the correlates of the risk of HBV infection, and the association with outcomes of ART among PLWH attending a busy HIV clinic in a referral hospital in Northern Uganda.

Patients And Methods: From April to June 2016, a random sample of 1000 PLWH attending the outpatients' clinic of St. Mary's Hospital, Gulu, Uganda were systematically selected to undergo a rapid hepatitis B surface antigen (HBsAg) test after administering a questionnaire in this cross-sectional study. HIV care parameters were obtained from client files. Multivariate logistic regression and general linear model were used for the analysis.

Results: 950 of the 985 evaluable patients (77% females; mean age 42.8 years) were receiving ART. The overall prevalence of HBsAg was 7.9% (95% confidence interval [CI] 6.2-9.6%), and was significantly lower among the females (6.8% vs 11.7%; p = 0.020). The factors independently associated with higher HBV infection were having lived in an internally displaced persons' camp (adjusted odds ratio [aOR] 1.76, 95% CI 1.03-2.98; p = 0.036) and having shared housing with HBV-infected people during childhood (aOR 3.30, 95% CI 1.49-7.32; p = 0.003). CD4+ T cell counts were significantly lower in HBV patients (p = 0.025), and co-infection was associated with a poorer CD4+ T cell response to ART (AOR 0.88; 95% CI 0.79-0.98; p = 0.030).

Conclusions: The observed prevalence of HBV among the PLWH may be underestimated or a signal of HBV decline in the region. The factors favouring horizontal HBV transmission identified suggest extending HBV screening and vaccine prophylaxis among PLWH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242278PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673526PMC
December 2020

The impact of PrEP: results from a multicenter Health Technology Assessment into the Italian setting.

J Prev Med Hyg 2020 Sep 6;61(3):E451-E463. Epub 2020 Oct 6.

MEng, Centre for Health Economics, Social and Health Care Management, LIUC-Università Cattaneo, Castellanza, Italy - School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Introduction: The use of oral tenofovir/emtricitabine (FTC/TDF) for pre-exposure prophylaxis (PrEP) among high-risk people without Human Immunodeficiency Virus (HIV), is emerging as an innovative strategy to decrease HIV epidemic. The study aims at evaluating the implications related to PrEP introduction, from a multidimensional point of view, as required by Health Technology Assessment (HTA) approach, with a particular attention on sustainability and social factors, influencing PrEP implementation.

Methods: An analysis was conducted involving 35 Italian Infectious Disease Departments. The introduction of PrEP (applied both as "add-on" and "substitute" prevention strategy) into the clinical practice was compared with a baseline scenario, consisting of condoms among men who have sex with men, and serodiscordant couples, and the use of Needle Syringe Programme among injection drugs users The above scenarios were analysed by means of a Health Technology Assessment (HTA) approach. The 9 EUnetHTA Core Model domains were assessed through comparative information, retrieved from literature evidence, and collection of qualitative and quantitative information, derived from real-world evidence, in particular from 35 Infectious Disease Departments and potential PrEP' users involved. A final multi-criteria decision analysis approach (MCDA) was implemented to simulate the appraisal phase and providing evidence-based information with regard to the preferable technology.

Results: Despite the improvement in patients' quality of life, PrEP would generate the development of other sexually transmitted and blood-borne diseases, with a consequent decrease of patients' safety in case of PrEP applied as a "substitute" prevention strategy. In addition, PrEP would generate an increase in staff workflow, with investment in medical supplies and training courses. PrEP would lead to significant economic investments both for the NHS (+40%), and for citizens (+2,377%) if used as an add-on strategy, assuming FTC/TDF patent cost. With the off-patent drug, the NHS would benefit from an advantage (37%), and a shrink of the patients' expenditure emerged (+682%). More economic resources are required if PrEP is applied as a substitute strategy, considering both the patent (NHS: 212%; citizens: 3,423%) and the off-patent drug (NHS: 73%; citizens: 1,077%). Conclusions. The most cost-containing strategy would be the use of PrEP, as an add-on strategy, with a consequent improvement in patients' safety, even if drug-related adverse events would be considered. The implementation of the off-patent drug would decrease the economic burden of the innovative prevention strategy. Hence, the organizational aspects related to its adoption would be deeply investigated, with the potential opportunity to create specific ambulatories devoted to PrEP users' especially for medium and big size hospitals.
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http://dx.doi.org/10.15167/2421-4248/jpmh2020.61.3.1352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595079PMC
September 2020

Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials.

J Acquir Immune Defic Syndr 2020 12;85(4):498-506

GlaxoSmithKline, Uxbridge, Middlesex, United Kingdom.

Background: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1.

Setting: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies.

Methods: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints.

Results: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm.

Conclusion: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.
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http://dx.doi.org/10.1097/QAI.0000000000002466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592884PMC
December 2020

Retinal findings in patients with COVID-19: Results from the SERPICO-19 study.

EClinicalMedicine 2020 Oct 20;27:100550. Epub 2020 Sep 20.

Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milan, Italy.

Background: Coronavirus disease 2019 (COVID-19) has been associated to microvascular alterations. We screened the fundus of patients with COVID-19 to detect alterations of the retina and its vasculature and to assess possible correlations with clinical parameters.

Methods: Cross-sectional study. The presence of retinal alterations in patients with COVID-19 and subjects unexposed to the virus was assessed using fundus photographs and their prevalence was compared. Mean arteries diameter (MAD) and mean veins diameter (MVD) were compared between patients and unexposed subjects with multiple linear regression including age, sex, ethnicity, body mass index, smoking/alcohol consumption, hypertension, hyperlipidaemia, diabetes as covariates. The influence of clinical/lab parameters on retinal findings was tested in COVID-19 patients.

Findings: 54 patients and 133 unexposed subjects were enrolled. Retinal findings in COVID-19 included: haemorrhages (9·25%), cotton wools spots (7·4%), dilated veins (27·7%), tortuous vessels (12·9%). Both MAD and MVD were higher in COVID-19 patients compared to unexposed subjects (98·3 ± 15·3 µm vs 91·9 ± 11·7 µm,  = 0.006 and 138·5 ± 21·5 µm vs 123·2 ± 13·0 µm, <0.0001, respectively). In multiple regression accounting for covariates MVD was positively associated with COVID-19 both in severe (coefficient 30·3, CI95% 18·1-42·4) and non-severe (coefficient 10·3, CI95% 1·6-19·0) cases compared to unexposed subjects. In COVID-19 patients MVD was negatively correlated with the time from symptoms onset (coefficient -1·0, CI 95% -1·89 to -0·20) and positively correlated with disease severity (coefficient 22·0, CI 95% 5·2-38·9).

Interpretation: COVID-19 can affect the retina. Retinal veins diameter seems directly correlated with the disease severity. Its assessment could have possible applications in the management of COVID-19.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2020.100550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502280PMC
October 2020

Short-term inhibition of SARS-CoV-2 by hydrogen peroxide in persistent nasopharyngeal carriers.

J Med Virol 2021 03 24;93(3):1766-1769. Epub 2020 Sep 24.

Department of Infectious Diseases, "Luigi Sacco" University Hospital, Milano, Italy.

Asymptomatic and convalescent coronavirus disease 2019 (COVID-19) subjects may carry severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for months in their upper respiratory ways. Desiring to permanently clean the mucosal surfaces, we investigated the chemical agents that fit to rapidly degrade the virus. Among these, hydrogen peroxide, initially tested by two of us for tolerability, showed both good performance and acceptable side effects (burning sensation for 15-20 s). We contacted circles of family physicians and the ATS Milano (Territorial Assistance and Prevention Service), and we tested this procedure on eight persistent carriers of SARS-CoV-2, performing swabs before the procedure and after it until the reappearance of the virus or until 14 days (the incubation period), keeping the surfaces clean with a hypertonic solution. Our patients had a median time from exposure or symptom onset of 111 days, and three had relapsed after being declared "cured" (two consecutive negative swabs after quarantine). One patient had a baseline negative swab and was excluded, and two successfully ended the 14 days' course, four suppressed viral elimination for 72 h, and one for 48 h, all rebounding to weak positive (cycle thresholds above 24). Although temporarily effective, such measures may have some place in the control of viral shedding to protect the most fragile subjects.
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http://dx.doi.org/10.1002/jmv.26485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891345PMC
March 2021

Comorbidities and HCV coinfection in the management of HIV+ patients: evidence from the Italian clinical practice.

Health Econ Rev 2020 Aug 29;10(1):27. Epub 2020 Aug 29.

Centre for Research on Health Economics, Social and Health Care Management, LIUC-Università Cattaneo, Castellanza, Italy.

Background: Since HIV+ treatment has become more effective, the average age of people living with HIV (PLWHIV) has increased, and consequently the incidence of developing comorbidities, making the clinical and economic management of HIV+ patients more complex. Limited literature exists regarding the management of comorbidities costs. This study is aimed at defining and comparing the total annual costs of comorbidities, in an Italian cohort of HIV and HIV/HCV patients, from the National Healthcare Service perspective. The authors hypothesised that there are higher costs, for patients with multiple comorbidities, and a greater consumption of resources for HIV/HCV co-infected patients versus HIV mono-infected patients.

Methods: An observational retrospective multi-centre health-economics study, enrolling HIV+ and HIV/HCV consecutive patients with at least one comorbidity, was conducted. The consecutive cases, provided by three Italian infectious diseases centres, were related to the year 2016. The enrolled patients were on a stable antiviral therapy for at least six months. Demographic and clinical information was recorded. Costs related to HIV and HCV therapies, other treatments, medical examinations, hospitalizations and outpatient visits were evaluated. Data from mono-infected and co-infected groups of patients were compared, and the statistical analysis was performed by t-tests, chi-square and ANOVA. A sub-analysis excluding HCV therapy costs, was also conducted. The hierarchical sequential linear regression model was used to explore the determinants of costs, considering the investigated comorbidities. All analyses were conducted with a significant level of 0.05.

Results: A total of 676 patients, 82% male, mean age 52, were identified and divided into groups (338 mono-infected HIV+ and 338 co-infected HIV/HCV patients), comparable in terms of age, gender, and demographic characteristics. A trend towards higher annual costs, for patients with multiple comorbidities was observed in HIV mono-infected patients (respectively € 8272.18 for patients without comorbidities and € 12,532.49 for patients with three or more comorbidities, p-value: 0.001). Excluding anti-HCV therapies costs, HIV/HCV co-infected patients generally required more resources, with statistically significant differences related to cardiovascular events (€10,116.58 vs €11,004.28, p-value: 0.001), and neurocognitive impairments events (€7706.43 vs €11,641.29 p- value: < 0.001).

Conclusions: This study provides a differentiated and comprehensive analysis of the healthcare resources needed by HIV and HIV/HCV patients with comorbidities and may contribute to the decision process of resources allocation, in the clinical management of different HIV+ patient populations.
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http://dx.doi.org/10.1186/s13561-020-00284-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456501PMC
August 2020

Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study).

Expert Rev Anti Infect Ther 2020 12 14;18(12):1271-1279. Epub 2020 Aug 14.

Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo E Carlo, University of Milan , Milan, Italy.

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and 'other sites' infections' (OTA).

Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016-2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting.

Results: 206 patients enrolled (males 50%, median age 62 [IQR 50-76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI 90.7% OTA (p = 0.003) and 46.3% ABSSSI 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure . Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5-22 3, 0-11.7; p<0.0001) and received longer previous (18 days, 9-30 11, 7-19; p = 0.007)/concomitant antibiotic treatments (21 days, 14-52 11, 8-14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% 75%, p = 0.459) and safety (no AE: 81.5% 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies.

Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use.
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http://dx.doi.org/10.1080/14787210.2020.1798227DOI Listing
December 2020

Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.

J Med Virol 2021 03 28;93(3):1421-1427. Epub 2020 Sep 28.

Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.
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http://dx.doi.org/10.1002/jmv.26407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436522PMC
March 2021

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings.

J Clin Virol 2020 09 11;130:104534. Epub 2020 Jul 11.

Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy. Electronic address:

Background: Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting.

Study Design: Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure.

Results: Among 798 patients analysed, 38.6 %, 27.1 % and 34.3 % received raltegravir, elvitegravir and dolutegravir, respectively. Baseline resistance to NRTIs, NNRTIs, PIs and INIs was: 3.9 %, 13.9 %, 1.6 % and 0.5 %, respectively. Overall, by 12 months of treatment, the probability of VS was 95 %, while the probability of VR by 36 months after VS was 13.1 %. No significant differences in the virological response were found according to the INI used. The higher pre-therapy viremia strata was (<100,000 vs. 100,000-500,000 vs. > 500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P < 0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count <200 cell/mm was associated with the lowest probability of VS (91.5 %, P < 0.001) and the highest probability of VR (20.7 %, P = 0.008) compared to higher CD4 levels. Multivariable Cox-regression confirmed the negative role of high pre-therapy viremia and low CD4 cell count on VS, but not on VR. Forty-three (5.3 %) patients experienced VF (raltegravir: 30; elvitegravir: 9; dolutegravir: 4). Patients failing dolutegravir did not harbor any resistance mutation either in integrase or reverse transcriptase.

Conclusions: Our findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice.
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http://dx.doi.org/10.1016/j.jcv.2020.104534DOI Listing
September 2020

Imported dengue fever: a 16-years retrospective analysis in Milan (Italy) and a brief review of the European literature.

Infez Med 2020 Jun;28(2):243-252

Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Universitá degli Studi di Milano, Milano; III Divisione di Malattie Infettive, ASST Fatebenefratelli Sacco, Universitá degli Studi di Milano, Milano.

Dengue Fever (DF), transmitted by Aedes mosquitoes, is the most common arthropod-borne infection, it is almost ubiquitous in tropical and subtropical areas with an estimate of 360 million infections per year. A competent vector (A. albopictus) is present in most of Southern Europe and is endemic in Italy. We conducted a 16-year retrospective study of probable/confirmed dengue fever observed at the Department of Infectious Diseases of Luigi Sacco Hospital in Milan, Italy. Overall 122 patients were included in the study, 106 with probable and 16 with proven diagnosis of dengue fever. Most patients (91%) were Italian, with a median age of 35 years (IQR 29-46 years) and similar gender distribution, travelling for tourism (80%). Asia (mainly South East Asia and Indian Subcontinent) was the most frequent travel destination (55%), followed by Central America and the Caribbeans (22%). August-September was the peak season of presentation (42.6%). The majority of our diagnoses were based on serology alone. The most common signs and symptoms were fever (99,2%), maculopapular rash (50,8%), headache (50,8%), arthralgias (50,8%) and myalgias (46,7%). Leukopenia (77%), thrombocytopenia (81%) and altered LDH, AST and ALT (respectively 60,6%, 54,1% and 45,9%) were the most common laboratory test's abnormalities. No cases of severe DF were recorded. Our epidemiological and clinical findings are largely in accordance with most recent studies about imported DF in Europe. Although very similar in presentation to other arthropod-borne illnesses, some clinical features may help in differentiating DF from other causes of fever in the returning traveler.
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June 2020

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.

Eur J Intern Med 2020 06 21;76:36-42. Epub 2020 May 21.

Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy.

Background: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19.

Methods: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days.

Results: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%).

Conclusion: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.
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http://dx.doi.org/10.1016/j.ejim.2020.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241995PMC
June 2020

30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: A prospective cohort study.

Pharmacol Res 2020 08 22;158:104931. Epub 2020 May 22.

Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy; Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Italy.

Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6 %) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1 %) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7 % (95 % CI 14.6-24.9 %) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95 % CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95 % CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95 % CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95 % CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95 % CI 1.37-4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20 %. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.
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http://dx.doi.org/10.1016/j.phrs.2020.104931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242199PMC
August 2020

Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status.

Pharmacol Res 2020 08 11;158:104899. Epub 2020 May 11.

Luigi Sacco Department of Biomedical and Clinical Sciences, University of Milan, Italy; Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milan, Italy.

SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94 % in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.
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http://dx.doi.org/10.1016/j.phrs.2020.104899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212963PMC
August 2020

Genomic characterization and phylogenetic analysis of SARS-COV-2 in Italy.

J Med Virol 2020 Sep 10;92(9):1637-1640. Epub 2020 Apr 10.

Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.

This report describes the isolation, molecular characterization, and phylogenetic analysis of the first three complete genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from three patients involved in the first outbreak of COVID-19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS-CoV-2 was present in Italy weeks before the first reported cases of infection.
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http://dx.doi.org/10.1002/jmv.25794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228393PMC
September 2020

COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome?

Clin Exp Rheumatol 2020 Mar-Apr;38(2):337-342. Epub 2020 Mar 22.

Department of Biomedical and Clinical Sciences 'Luigi Sacco', University of Milan, and III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy.

A severe outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019, and spread so rapidly that more than 200,000 cases have so far been reported worldwide; on January 30, 2020, the WHO declared it the sixth public health emergency of international concern. The two previously reported coronavirus epidemics (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) share similar pathogenetic, epidemiological and clinical features as COVID-19. As little is currently known about SARS-CoV-2, it is likely that lessons learned from these major epidemics can be applied to the new pandemic, including the use of novel immunosuppressive drugs.
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April 2020

Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression.

N Engl J Med 2020 03 4;382(12):1112-1123. Epub 2020 Mar 4.

From the University of Nebraska Medical Center, Omaha (S.S.); Centro Universitario de Ciencias de la Salud, University of Guadalajara, Guadalajara, Mexico (J.-F.A.-V.); Broward Health Medical Center, Broward Health Imperial Point, Fort Lauderdale, FL (G.J.R.); Fatebenefratelli Sacco Hospital, Milan (G.R.); the Center for Infectious Diseases, Berlin (A.B.); Hospital de Elche, Elche, Spain (M.M.); Maxwell Centre, Durban, South Africa (G.L.); the Central Research Institute of Epidemiology, Moscow (V.P.); Metropolis Medical Group, San Francisco (F.B.); Maple Leaf Research, Toronto (G.S.), and GlaxoSmithKline, Mississauga (J.H.) - both in Ontario, Canada; Fundación Huésped, Buenos Aires (P.C.); Chungnam National University School of Medicine, Daejeon, South Korea (Y.-S.K.); GlaxoSmithKline (S.L.F.) and ViiV Healthcare (C.L.T., P.P., J.M., C.M.H., K.J.H., D.A.M., K.Y.S., W.R.S.) - both in Research Triangle Park, NC; ViiV Healthcare, Brentford, United Kingdom (V.C.); and Janssen Research and Development, Beerse, Belgium (H.C., W.P., S.V., P.E.W.).

Background: Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.

Methods: In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm.

Results: Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group.

Conclusions: Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).
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http://dx.doi.org/10.1056/NEJMoa1904398DOI Listing
March 2020

Comparison of three therapeutic regimens for genotype-3 hepatitis C virus infection in a large real-life multicentre cohort.

Liver Int 2020 04 3;40(4):769-777. Epub 2020 Feb 3.

ASST Bergamo Ovest, Treviglio, Italy.

Background & Aims: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap.

Methods: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression.

Results: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log HCV-RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12.

Conclusions: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this genotype.
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http://dx.doi.org/10.1111/liv.14386DOI Listing
April 2020