Abstract Background We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART. Methods All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR’s group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels. Results Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG. No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR’s groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001 ] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027 ]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001 ] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001 ] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478]. Conclusion No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch.
OBJECTIVE Obesity is an established risk factor for severe coronavirus disease 2019 (COVID-19), but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMI-associated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODS We retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Site-specific estimates were combined in a meta-analysis. RESULTS Among 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15–1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03–1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74–1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONS In adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.
International guidelines recommend the use of integrase strand transfer inhibitor (INI)-based regimens as first-line antiretroviral (ARV) in both naive and experienced HIV-infected patients. We analyzed a multicenter cohort of HIV-infected patients, both naive and experienced, starting an ARV, including an INI. Chi-square test and nonparametric tests were used to assess differences in categorical and continuous variables, respectively. Kaplan-Meier survival analysis was performed to estimate the probability of maintaining the study drug and Cox-regression analysis to evaluate predictors of discontinuation. We enrolled 4,343 patients: 3,143 (72.4%) were males, with a median age of 49 years (interquartile range 41-55). Naive patients were 733 (16.9%), of whom 168 (22.9%) were AIDS presenters. Overall, 2,282 patients (52.5%) started dolutegravir (DTG), 1,426 (32.8%) raltegravir (RAL), and 635 (14.7%) elvitegravir (EVG). During 10,032 patient years of follow-up (PYFU), we observed 1,278 discontinuations (13 per 100 PYFU); 448 of them (35%) due to simplification and 355 (28%) to toxicities (98 for central nervous system toxicity). Reasons of discontinuation were different between INIs. Estimated probability of maintaining DTG at 3 and 4 years were 81.5% [95% confidence interval (CI): 80.5-82.5] and 76.3% (95% CI: 73.9-78.7), respectively; RAL 61.6% (95% CI: 60.2-63.0) and 54.1% (95% CI: 52.7-55.5); EVG 71.6% (95% CI: 69.2-74.0) and 68.3% (95% CI: 65.3-71.3) (p < .001). At a multivariable analysis, being on a RAL-based ARV [vs. DTG, adjusted hazard ratio (aHR) 2.9, 95% CI: 2.3-3.6, p < .001], a EVG-based ARV (vs. DTG, aHR 1.3 95% CI: 1.1-1.7, p = .049), and a peak HIV-RNA >500k cp/mL (aHR 1.3, 95% CI: 1.1-1.6, p = .006) predicted INI discontinuation. Our data confirm the good tolerability of INIs in clinical practice. Differences emerge between the three drugs in reasons for discontinuation.
The powerful drugs with direct antiviral action (DAA) against hepatitis C virus (HCV) has made it possible to eliminate the trigger factor of Mixed Cryoglobulin Syndrome (MCS) and to extend the treatment to patients who could not tolerate IFN-based antiviral regimens. However, the persistence of cryoglobulin production and MCS-related symptoms despite SVR achievement is frequently reported.
Objectives:
The aim of this study was to assess the persistency rate of MCS-related clinical and laboratory indexes after successful treatment with DAA.
Methods:
CRESO (CRyoglobulinaemia Eradication Study Observational) is a multicentre observational study promoted by the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Group for the Study of Cryoglobulinaemias (GISC), aimed to assess the impact of DAA therapy on MCS symptoms and cryoglobulin production. Patients could be enrolled if they presented, during the 12 months before the enrolment, a cryocrit ≥0.5% and, at least, one episode of palpable purpura or, alternatively, arthralgia and fatigue with at least one symptom among peripheral neuropathy, Raynaud's phenomenon, lower limb ulcers or nephropathy, and a C4 level ≤8 mg/dL.
Results:
The present analysis was based on clinical and laboratory data of 94 patients (75.5% female with a median age of 67.5 years) that have been followed up for a median time of 24 weeks (IQR 12-24) after SVR12 achievement. At baseline the cryocrit was frankly positive in 85 (90.43%), detectable (>0.5%) in 4 and negative in 4 cases; patients with type II cryoglobulins and C4levels ≤8 mg/dL were prevalent, respectively with 81.5% and 75.9%. Low eGFR values (≤45 mL/min/1.73m2) were present in 12 cases (12.8%), 10 patients (10.6%) had a history of B-cell non-Hodgkin's lymphoma (NHL), and 1 of hepatocellular carcinoma, while liver cirrhosis was diagnosed in 22 cases (23.4%) and glomerulonephritis in 17 cases (18.1%). Patients were treated for 12 (72 cases) or 24 (21 cases) weeks with a total of ten different IFN-free DAA regimens. SVR12 was achieved in all 94 cases. Both prevalence and median cryocrit values decreased significantly after DAA treatment (p<0.0001), however, at the time of the last observation 56.4% of patients were still positive for MCs. The prevalence of purpura and fatigue significantly decreased (p<0.0001) as well sicca syndrome prevalence (p<0.015), while arthralgia and lower limb ulcers decrease did not reach statistical significance. In multivariate analysis, eGFR≤45 mL/min/1.73m2 was an independent predictor of persistence of cryoglobulin production (AOR 7.7, CI 95% 1.6-37.2; p<0.011).
Conclusion:
CRESO study data confirm the persistence of cryoglobulin production and MCS symptoms in some patients, despite the eradication of HCV. This finding rises questions about the possible further evolution of the disease over time regardless the persistence of its original trigger.
The first wave of the COVID-19 epidemic in Italy during March and April 2020 put extreme pressure on the national healthcare system, particularly on the hospitals in the most affected regions of northern Italy. Although the drastic measures taken to contain SARS-CoV-2 transmission (including a nationwide lockdown) led to a marked decrease in the number of new COVID-19 cases and deaths during the summer, the number of new cases is currently rising again at an alarming rate [1Covid-19 - Situazione in Italia. http://opendatadpc.maps.arcgis.com/apps/opsdashboard/ index.html#/b0c68bce2cce478eaac82fe38d4138b.Google Scholar], and the coming winter raises further concerns about the additional effects the seasonal influenza epidemic will have on already stressed healthcare services. Both influenza and COVID-19 can present with non-specific symptoms (fever, myalgia, headache, non-productive cough and shortness of breath), most of which are self-limiting but may also progress to severe conditions. Moreover, like COVID-19, influenza puts older people and those with chronic medical conditions at higher risk of morbidity and mortality [2Clark A Jit M Warren-Gash C Guthrie B Wang HHX Mercer SW et al.Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study.Lancet Glob Health. 2020; 8: e1003-e1017https://doi.org/10.1016/S2214-109X(20)30264-3Abstract Full Text Full Text PDF PubMed Scopus (698) Google Scholar, 3Nicoll A Ciancio B Tsolova S Blank P Yilmaz C. The scientific basis for offering seasonal influenza immunisation to risk groups in Europe.Euro Surveill. 2008; 13: 19018https://doi.org/10.2807/ese.13.43.19018-enCrossref PubMed Scopus (41) Google Scholar, 4Demicheli V Jefferson T Di Pietrantonj C Ferroni E Thorning S Thomas RE et al.Vaccines for preventing influenza in the elderly.Cochrane Database Syst Rev. 2018; 2CD004876PubMed Google Scholar]. This is why extended influenza vaccination programmes aimed particularly at such risk groups are more than ever necessary to avoid the overload of health services and hospitals due to the concomitant diffusion of influenza and COVID-19 infections with the subsequent challenge of differential diagnosis. However, this means overcoming the existing barriers to vaccinations that are responsible for the historical sub-optimal use of influenza vaccine in many countries (including Italy, where it is offered free of charge to people at high risk and healthcare providers) [5European Centre for Disease Prevention and ControlSeasonal influenza vaccination and antiviral use in EU/EEA Member States – overview of vaccine recommendations for 2017–2018 and vaccination coverage rates for 2015–2016 and 2016–2017 influenza seasons. ECDC, Stockholm2018Google Scholar]. In a bid to contextualise this issue, we have analysed the patients living in the province of Milan who were admitted to our referral COVID-19 centre between 21 February and 31 May 2020 in order to calculate the proportion who received the influenza vaccination for the 2019-2020 season. The data regarding seasonal influenza vaccination uptake were extracted from the electronic immunisation register of Milan's Health Protection Agency. The study population consisted of 428 subjects (146 females and 282 males with a median age of 60.6 years, range 48.9-72.7), of whom 335 (78.3%) belonged to one or more of the categories for which influenza vaccination is recommended by the Italian national immunisation guidelines: 174 (40.7%) were aged ≥65 years, 291 (68.0%) had underlying chronic diseases, and 57 (13.1%) were healthcare workers. However, only 109 of the patients who should have been vaccinated actually received the vaccine: 44.2% of those aged ≥65 years, 33.0% of those with underlying chronic diseases, and 31.6% of healthcare workers. Our data show disappointingly low influenza vaccination coverage among the subjects at risk and healthcare workers admitted to our COVID-19 centre during the first wave of the epidemic. Particularly in the elderly the coverage was far below the minimum recommended threshold of 75% and consistent with the worrying decline of influenza vaccination registered in Lombardy over the last decade [6Rossi D Croci R Affanni P Odone A Signorelli C. Influenza vaccination coverage in Lombardy Region: a twenty-year trend analysis (1999-2019).Acta Biomed. 2020; 91: 141-145https://doi.org/10.23750/abm.v91i3-S.9455Crossref PubMed Scopus (4) Google Scholar]. This clearly calls for the prompt reinforcement of the seasonal influenza vaccination information campaign and a greater supply of vaccine in order to make the most of the benefits of influenza vaccination for individual well-being and the functioning of the healthcare system at large over such a critical time. Moreover, emerging data suggest that influenza vaccinations may have a protective effect against the risk of experiencing severe COVID-19, especially among high-risk groups [7Amato M Werba JP Frigerio B Coggi D Sansaro D Ravani A et al.Relationship between Influenza vaccination coverage rate and COVID-19 outbreak: an Italian ecological study.Vaccines. 2020; 8: E535https://doi.org/10.3390/vaccines8030535Crossref Scopus (95) Google Scholar, 8Zanettini C, Omar M, Dinalankara W, Imada EL, Colantuoni E, Parmigiani G, et al. Influenza vaccination and COVID19 mortality in the USA. Preprint. medRxiv. 2020;2020.06.24.20129817. Published 2020 Jun 26. doi:10.1101/2020.06.24.20129817.Google Scholar, 9Fink G, Orlova-Fink N, Schindler T, Grisi S, Ferrer AP, Daubenberger C, et al. Inactivated trivalent influenza vaccine is associated with lower mortality among Covid-19 patients in Brazil. medRxiv 2020.06.29.20142505; DOI: https://doi.org/10.1101/2020.06.29.20142505.Google Scholar], which may be of paramount importance given the paucity of effective COVID-19 treatments, (Table 1).Table 1Vaccination coverage rate for influenza season 2019/2020 among patients hospitalized with COVID-19 in Milan, Italy.CharacteristicTotal (n=428)Vaccinated (109)Not vaccinated (319)Sex, n (%) Females146 (34.1)36 (24.7)110 (75.3) Males282 (65.9)73 (25.9)209 (74.1)Age, n (%) < 65254 (59.3)32 (12.6)222 (87.4) ≥ 65174 (40.7)77 (44.3)97 (55.7)Heath care workers57 (13.3)18 (31.6)39 (68.4)At least one underlying chronic disease, n (%)291 (68.0)96 (33.0)195 (67.0)Type of underlying comorbidities, n (%) Chronic lung disease68 (15.9)25 (36.8)43 (63.2) Heart disease202 (47.2)75 (37.1)127 (62.9) Diabetes mellitus53 (12.4)21 (39.6)32 (60.4) Chronic renal disease36 (8.4)14 (38.9)22 (61.1) Cancer41 (9.6)14 (34.1)27 (65.9) Immune disorders32 (7.5)10 (31.3)22 (68.8) Chronic liver disease10 (2.3)3 (30.0)7 (70.0) Open table in a new tab ALR, LM, and AG conceived the study, collected data and drafted the manuscript. LO conducted data analysis. SA and CB critically revised the manuscript. All of the authors contributed to writing the manuscript and approved the final version. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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.
Since antiretroviral therapy must be taken lifelong, persistence and safety have become the goals to achieve. Protease inhibitors, in particular atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed class in real life long-term treatment.We conducted a retrospective cohort study in HIV-1-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load, CD4 lymphocytes and the mean blood chemistry parameters were collected at baseline, first, third, sixth months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and time-dependent probability to reach a CD4 cells count >500 cells/µL were evaluated with Kaplan-Meier curve and Cox model.A total of 1030 patients were evaluated: 183 received therapy with ATV/r as naïve, 653 switched to ATV/r as a second or following line and 194 switched to unboosted ATV from previous ATV-free regimens. A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen (17 from naïve ATV/r and 121 from experienced ATV/r). The median duration of therapy was 38 months (95% CI 29-73) in ATV/r naïve patients, 36 months (95% CI 23-53) in unboosted ATV group and 35 months (95% CI 31-43) in patients switched to ATV/r. We observed no significant difference in the persistence of the three regimens (p=0.149). Female (HR=1.317; 95% CI 1.073-1.616 p=0.008) and patients with CD4<200 cells/µL at baseline (HR=1.433 95% CI 1.086-1.892 p=0.011) were at increased risk of regimen interruption, whereas starting therapy with a backbone containing abacavir (HR=0.725; 95% CI 0.533-0.987 p=0.041) resulted protective. In multivariate analysis no significant difference between the three regimens was observed regarding reaching a count of CD4 cells >500 cells/µL. Factors associated to a poor CD4 gain were each extra Log of viral load at baseline (HR=0.915; 95% CI 0.852-0.982 p=0.014) and CD4<200 cells/µL at ATV start (HR=0.197; 95%CI 0.138-0.281 p<0.0001); conversely, females (HR=1.262; 95%CI 1.032-1.543 p=0.023) had a higher probability of CD4 recovery.Antiretroviral regimens containing atazanavir with or without ritonavir were durable and well tolerated, an elevated viral load and CD4 <200 cells/µL at baseline resulted related to regimen discontinuation and reduced CD4 recovery.
Background: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for drug-drug interactions (DDIs). The pharmacological burden may be further aggravated by the addition of treatments for SARS-CoV-2 infection. Methods: The aim of this study was to assess the risk of potential DDIs upon admission and during hospitalisation in 502 COVID-19 patients treated at our hospital. We for all patients with a proven diagnosis of SARS-CoV-2 infection hospitalised between 21 February and 30 April 2020 and treated with at least two drugs. Findings: Overall, 68% of our COVID-19 patients were exposed to at least one potential DDI and 55% to at least one potentially severe DDI. The proportion of patients experiencing severe DDIs increased from 22% upon admission to 80% during hospitalisation. Furosemide, amiodarone and quetiapine were the main drivers of severe DDIs upon admission, and hydroxychloroquine and particularly lopinavir/ritonavir were the main drivers during hospitalisation. The large majority of severe DDIs carried an increased risk of cardiotoxicity. No severe DDIs were identified in relation to tocilizumab and remdesivir. Interpretation: Among hospitalised COVID-19 patients, concomitant treatment with lopinavir/ritonavir and hydroxychloroquine led to a dramatic increase in the number of severe DDIs. Given the high risk of cardiotoxicity and the scanty and conflicting data concerning their efficacy in treating SARS-CoV-2 infection, the use of lopinavir/ritonavir and hydroxychloroquine in COVID-19 patients with polypharmacy needs to be carefully considered.Funding Statement: No funds were received for this study.Declaration of Interests: We declare no competing interest for the present study. CG has received personal fees from MSD, ViiV, Gilead and Janseen Cilag unrelated to this study. DC has received personal fees from MSD, ViiV, and Janseen Cilag unrelated to this study. APM has received personal fees from Bayer, Fresenius, and Novartis for participating in study committees unrelated to this study All of the other authors declare that they have no potential conflict of interest.Ethics Approval Statement: The study was approved by our hospital's Ethics Committee (Comitato Etico Interaziendale Area 1). All of the patients included in the study signed an informed consent form for the administration of off-label treatments.
