Lipid profile improvement in virologically suppressed hiv-1-infected patients switched to dolutegravir/ abacavir/lamivudine: Data from the SCOLTA project

open13noIntroduction: Metabolic disorders are common amongst HIV-infected patients. Data from real-life setting on the impact of DTG/ABC/3TC in virologically suppressed HIV-infected patients are scarce. Methods: We investigated the modification of metabolic profile including fasting glucose, lipid profile and markers of insulin resistance (IR) in experienced patients switching from a boosted protease inhibitors (bPI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to DTG/ABC/3TC in a prospective, observational, multicenter study. Results: We enrolled 131 HIV-infected patients, of whom 91 (69.5%) males, mean age was 50.5±10.6 years. CDC stage was A in 66 (50.4%) patients, of whom 91 (69.5%) had acquired HIV through sexual contacts. The previous regimen was bPI-based in 79 patients (60.3%) and NNRTI-based in 52 (39.7%). Patients switching from NNRTI showed a significant reduction at week 24 in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL). Triglycerides/high-density lipoprotein cholesterol (TG/HDL) ratio, HDL, median TG and TG/HDL ratio did not show significant modification during follow-up times. Among patients switching from a bPI, we observed a significant reduction in TC and LDL at both follow-up times and a slight increase in HDL. Triglycerides/HDL ratio, median TG and TG/HDL ratio showed a decrease over time that became significant at weeks 24 and 48. Blood glucose levels did not significantly vary during the observation period in patients switching from both bPI and NNRTI-based regimens. Conclusion: Our data suggest an improvement in lipid profile and TG/HDL ratio in pretreated HIV-1-infected patients who switched to DTG/ABC/3TC over 48 weeks, especially in those previously receiving a bPI-based regimen.openBagella P.; Squillace N.; Ricci E.; Gulminetti R.; De Socio G.V.; Taramasso L.; Pellicano G.; Menzaghi B.; Celesia B.M.; Dentone C.; Orofino G.; Bonfanti P.; Madeddu G.Bagella, P.; Squillace, N.; Ricci, Elena; Gulminetti, R.; De Socio, G. V.; Taramasso, L.; Pellicano, G.; Menzaghi, B.; Celesia, B. M.; Dentone, C.; Orofino, G.; Bonfanti, P.; Madeddu, G

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

Background: In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). Methods: To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50–59 and 60–69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years). Results: In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20– 1.52), hypertension (aRR 1.52, 95% CI 1.22–1.89), liver disease (aRR 1.78, 95% CI 1.32–2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65–5.03) and multimorbidity (aRR 1.36, 95% CI 1.21–1.54). These findings were confirmed in strata of age, adjusting for sex. Conclusions: Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age

Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: Results from a large observational cohort study (SCOLTA)

Background: Dyslipidemia represents a significant non-infectious comorbidity among people living with HIV. The aim of this study is to evaluate the impact on lipid profile of switches from an efavirenz (EFV) or protease inhibitor/ritonavir (PI/r)-based regimen to a rilpivirine (RPV) or a once-daily integrase inhibitor-based regimen. Methods: We analyzed data from SCOLTA prospective database. All patients with HIV-RNA < 50 copies/ml in therapy with two NRTI + EFV or PI/r were included if they switched from EFV to dolutegravir (group EFV-DTG), elvitegravir (EFV-EVG), or RPV (EFV-RPV) and from PI/r to DTG (PI/r-DTG), PI/r to EVG (PI/r-EVG), or PI/r to RPV (PI/r-RPV). Total cholesterol (TC), TC/HDL ratio, LDL-cholesterol (LDL) and triglycerides (TG) were compared at baseline, six months and one year. Comparisons among groups were performed by a general linear model. Results: Four hundred and ninety patients were enrolled, 24.9% female, mean age 47.3 years (\ub110.1). According to ART switch, 11.4% were classified in group EFV-DTG, 3.9% in EFV-EVG, 23.9% in EFV-RPV, 17.6% in PI/r-DTG, 17.8% in PI/r-EVG, and 25.5% in PI/r-RPV. After adjusted analysis, TC significantly decreased in all groups but EFV-EVG, TC/HDL in all but EFV-DTG and EFV-EVG, while the reduction of TG was significant only in switches to RPV (EFV-RPV and PI/r-RPV). The one year decrease of TC, TC/HDL, LDL and TG was higher in patients with higher baseline levels of the same variable (p < .0001 for all). Conclusions: In SCOLTA, all switches from PI/r regimens gave advantages on lipid profile, while stopping EFV had consistently favorable lipid effects only if replaced by RPV

Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

Background There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. Aim To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. Methods Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org). Results Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. Conclusions Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring" in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease

Decline of Prevalence of Resistance Associated Substitutions to NS3 and NS5A inhibitors at DAA-failure in Hepatitis C Virus in Italy over the years 2015 to 2018

Background: A minority of patients fail to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens. Material and methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols. The geno2pheno system was used to infer HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend, predictors of RASs at failure were analysed by logistic regression. Results: We included 386 real-life HCV pts failed to recommended DAA regimens: 92% (271/294) Italians, 75% (286/384) males, median age was 56 years (IQR 52-61); 106 (28%) were treatment-experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAA-based regimens. Metavir fibrosis stage was F4 in 76% (245/322), 65% (240/369) had clinical cirrhosis. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype (G) was G1b in 122 pts (32%), G3a 103 (27%), G1a 97 (25%), G4d 30 (8%), G2c 19 (5%), G3h 5 (1.3%), G4a 4 (1%) and 1 (0.3%) each for G3g, G4n/o/v. DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%). Antiviral treatment was completed by 352 pts (91%), while 34 (9%) discontinued prematurely. The NS5A fasta-sequence was available for all pts, NS5B for 361 (94%), NS3 for 365 (95%). The prevalence of any RASs was 87%, namely 78/135 (58%) in NS3, 303/359 (85%) in NS5A, 114/286 (40%) in NS5B (Tab 1). The prevalence of any RASs significantly declined from 2015 to 2018 (100%, 13/13 vs 81%, 101/125, p=0.01): NS5A RASs from 100%, 13/13 to 76%, 76/100 (p<0.001), NS3 RASs from 88%, 7/8 to 44%, 28/63 (p=0.02), while NS5B RASs remained stable. Independent predictors of any RASs included liver cirrhosis/advanced fibrosis (AOR 3.72, CI 95% 1.51-9.17, p=0.004) and genotype (G2 vs G1a AOR 0.01, CI 95% 0.0-0.3, p<0.001; G3 vs G1a AOR 0.22, CI 95% 0.05-0.98, p<0.047; G4 vs G1a AOR 0.13, CI 95% 0.03-0.63, p<0.011), with a modest effect scored for past treatment (AOR 3.45, CI 95% 1.00-11.92, p=0.05), after adjusting for DAA regimen and year of genotype. Notably, full activity was predicted for GLE/PIB in 75.9% of cases and for at least two components of VEL/SOF/VOX in 59% of cases and no case with full-resistance to either regimen was found (Tab 2). Conclusions: Despite decreasing prevalence over the years, RASs remain a common signature at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. Their distribution may vary according to genotype, so the identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy

none140noNAnoneColaneri M.; Seminari E.; Piralla A.; Zuccaro V.; Di Filippo A.; Baldanti F.; Bruno R.; Mondelli M.U.; Brunetti E.; Di Matteo A.; Maiocchi L.; Pagnucco L.; Mariani B.; Ludovisi S.; Lissandrin R.; Parisi A.; Sacchi P.; Patruno S.F.A.; Michelone G.; Gulminetti R.; Zanaboni D.; Novati S.; Maserati R.; Orsolini P.; Vecchia M.; Sciarra M.; Asperges E.; Sambo M.; Biscarini S.; Lupi M.; Roda S.; Chiara Pieri T.; Gallazzi I.; Sachs M.; Valsecchi P.; Perlini S.; Alfano C.; Bonzano M.; Briganti F.; Crescenzi G.; Giulia Falchi A.; Guarnone R.; Guglielmana B.; Maggi E.; Martino I.; Pettenazza P.; Pioli di Marco S.; Quaglia F.; Sabena A.; Salinaro F.; Speciale F.; Zunino I.; De Lorenzo M.; Secco G.; Dimitry L.; Cappa G.; Maisak I.; Chiodi B.; Sciarrini M.; Barcella B.; Resta F.; Moroni L.; Vezzoni G.; Scattaglia L.; Boscolo E.; Zattera C.; Michele Fidel T.; Vincenzo C.; Vignaroli D.; Bazzini M.; Iotti G.; Mojoli F.; Belliato M.; Perotti L.; Mongodi S.; Tavazzi G.; Marseglia G.; Licari A.; Brambilla I.; Daniela B.; Antonella B.; Patrizia C.; Giulia C.; Giuditta C.; Marta C.; Rossana D.; Milena F.; Bianca M.; Roberta M.; Enza M.; Stefania P.; Maurizio P.; Elena P.; Antonio P.; Francesca R.; Antonella S.; Maurizio Z.; Guy A.; Laura B.; Ermanna C.; Giuliana C.; Luca D.; Gabriella F.; Gabriella G.; Alessia G.; Viviana L.; Claudia L.; Valentina M.; Simona P.; Marta P.; Alice B.; Giacomo C.; Irene C.; Alfonso C.; Di Martino R.; Di Napoli A.; Alessandro F.; Guglielmo F.; Loretta F.; Federica G.; Alessandra M.; Federica N.; Giacomo R.; Beatrice R.; Maria S.I.; Monica T.; Nepita Edoardo V.; Calvi M.; Tizzoni M.; Nicora C.; Triarico A.; Petronella V.; Marena C.; Muzzi A.; Lago P.; Comandatore F.; Bissignandi G.; Gaiarsa S.; Rettani M.; Bandi C.Colaneri, M.; Seminari, E.; Piralla, A.; Zuccaro, V.; Di Filippo, A.; Baldanti, F.; Bruno, R.; Mondelli, M. U.; Brunetti, E.; Di Matteo, A.; Maiocchi, L.; Pagnucco, L.; Mariani, B.; Ludovisi, S.; Lissandrin, R.; Parisi, A.; Sacchi, P.; Patruno, S. F. A.; Michelone, G.; Gulminetti, R.; Zanaboni, D.; Novati, S.; Maserati, R.; Orsolini, P.; Vecchia, M.; Sciarra, M.; Asperges, E.; Sambo, M.; Biscarini, S.; Lupi, M.; Roda, S.; Chiara Pieri, T.; Gallazzi, I.; Sachs, M.; Valsecchi, P.; Perlini, S.; Alfano, C.; Bonzano, M.; Briganti, F.; Crescenzi, G.; Giulia Falchi, A.; Guarnone, R.; Guglielmana, B.; Maggi, E.; Martino, I.; Pettenazza, P.; Pioli di Marco, S.; Quaglia, F.; Sabena, A.; Salinaro, F.; Speciale, F.; Zunino, I.; De Lorenzo, M.; Secco, G.; Dimitry, L.; Cappa, G.; Maisak, I.; Chiodi, B.; Sciarrini, M.; Barcella, B.; Resta, F.; Moroni, L.; Vezzoni, G.; Scattaglia, L.; Boscolo, E.; Zattera, C.; Michele Fidel, T.; Vincenzo, C.; Vignaroli, D.; Bazzini, M.; Iotti, G.; Mojoli, F.; Belliato, M.; Perotti, L.; Mongodi, S.; Tavazzi, G.; Marseglia, G.; Licari, A.; Brambilla, I.; Daniela, B.; Antonella, B.; Patrizia, C.; Giulia, C.; Giuditta, C.; Marta, C.; D'Alterio, Rossana; Milena, F.; Bianca, M.; Roberta, M.; Enza, M.; Stefania, P.; Maurizio, P.; Elena, P.; Antonio, P.; Francesca, R.; Antonella, S.; Maurizio, Z.; Guy, A.; Laura, B.; Ermanna, C.; Giuliana, C.; Luca, D.; Gabriella, F.; Gabriella, G.; Alessia, G.; Viviana, L.; Meisina, Claudia; Valentina, M.; Simona, P.; Marta, P.; Alice, B.; Giacomo, C.; Irene, C.; Alfonso, C.; Di Martino, R.; Di Napoli, A.; Alessandro, F.; Guglielmo, F.; Loretta, F.; Federica, G.; Albertini, Alessandra; Federica, N.; Giacomo, R.; Beatrice, R.; Maria, S. I.; Monica, T.; Nepita Edoardo, V.; Calvi, M.; Tizzoni, M.; Nicora, C.; Triarico, A.; Petronella, V.; Marena, C.; Muzzi, A.; Lago, P.; Comandatore, F.; Bissignandi, G.; Gaiarsa, S.; Rettani, M.; Bandi, C

Positioning of darunavir/cobicistat-containing antiretroviral regimens in real life: Results from a large multicentre observational prospective cohort (SCOLTA)

Background: Study aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting. Methods: Multicentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables. Results: A total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 130 or statin use) was present in 121 (48.6%) and hypertriglyceridemia, (triglycerides (TG) ≥ 200 mg/dl or fibrate use) in 41 (16.5%) patients. Blood lipid profile did not change significantly in either the global population or patients with HC. After a median observation of 17 months (IQR 13-20), 59 (25.3%) patients discontinued DRV/c, of which 13 were in DT. The durability DT resulted higher than that of triple therapy (log-rank test p = 0.01). Main reasons for stopping DRV/c were simplification (15 patients), adverse events (13 patients), planned discontinuation for treatment initiation with DAA (4 patients), treatment failure (2 patients); death (2 patients), other causes (10 patients). Twenty-six were lost to follow-up. Conclusions: DRV/c was safe and well tolerated. Dual therapies showed a better profile of tolerability and a longer durability compared to triple therapies

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21\u201328 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age>65 years, antiviral treatment and for severe disease, lactate dehydrogenase >300 mg/dL

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted