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The aim of the present study was to evaluate CD4/CD8 dynamics in patients on dolutegravir (DTG)-based two-drug regimens (2DRs) and compare them with DTG-containing triple-drug regimens (3DRs). A prospective observational study was performed in the context of the SCOLTA cohort. Experienced PWH with HIV-RNAlt; 50 copies/mL were included if they were on the DTG-2DR, the DTG + tenofovir/emtricitabine (TDF/FTC) regimen, the DTG + tenofovir alafenamide (TAF)/FTC regimen, or the DTG + abacavir/lamivudine (ABC/3TC) regimen; they were followed-up for at least one year. A total of 533 PWH were enrolled, 120 in the DTG + 3TC group, 38 in the DTG + protease inhibitors (PI) group, 67 in the DTG + rilpivirine (RPV) group, 49 in the DTG + TDF/FTC group, 27 in the DTG + TAF/FTC group, and 232 in the DTG + ABC/3TC group. After one year, the CD4/CD8 ratio significantly increased in the PWH treated with DTG + 3TC (+0.08 ± 0.26), DTG + TDF/FTC (+0.1 ± 0.19), and DTG + ABC/3TC (+0.08 ± 0.25). At two years, the CD4/CD8 increase was confirmed for PWH on DTG + TDF/FTC (+0.16 ± 0.28) and DTG + ABC/3TC (+0.1 ± 0.3). In the SCOLTA cohort, PWH on 2DRs experienced a CD4/CD8 increase only in the DTG + 3TC group. Controlled studies with longer follow-up will clarify the long-term immunological and clinical impacts of DTG-2DR.

Objective We aimed to investigate the effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on the hepatic safety and metabolic profile. Methods Consecutive HIV patients, enrolled in the Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project, switching from TDF to TAF were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired t-test and signed rank test. Results A total of 190 patients switched from TDF to TAF and had one 6-month follow-up visit. They were 80% male, 74.2% at CDC stage A–B, 93.7% with undetectable HIV-viral load. Mean age was 46.7±10.7 years, body mass index was 25.0±3.9 kg/m2, median CD4 cell count was 634 cell/µL (interquartile range [IQR]=439–900), aspartate aminotransferase (AST) was 23 (IQR=19–30) IU/L, and alanine aminotransferase (ALT) was 24 (IQR=17–34) IU/L. At T1, both AST (median=−1, IQR=−5–2 IU/L, P=0.004) and ALT (median=−2, IQR=−7–3 IU/L, P=0.0004) showed a significant decrease. Among 28 patients with ALT >40 at baseline, reduction was significant both clinically (−17, IQR=−32–−1) and statistically (P=0.0003). Total cholesterol levels (TC) increased (+13.4±3.8 mg/dL, P=0.0006), as well as HDL-cholesterol (HDL-C) (+3.8±1.2 mg/dL, P=0.02), LDL Cholesterol (LDL-C) (+7.6±3.4, P=0.03) and glucose (+4.0±1.8 mg/dL, P=0.02). D:A:D: and Framingham risk score did not change at 6 months after switch. Conclusion A significant reduction of liver enzymes was observed after switching from TDF to TAF, especially in subjects with initial level of ALT >40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores.

Objective Few data exist about the effect of dolutegravir (DTG) on bone mineral density (BMD) in real life. The aim of this study was to determine rates of change in BMD over time in people living with HIV (PLWH) treated with DTG. Design The SCOLTA project is a multicenter observational study enrolling HIV-infected people who start newly commercialized drugs prospectively, with the aim of identifying toxicities and adverse events (AE) in a real-life setting. Methods Dual-energy X-ray absorptiometry at the femoral neck (FN) and lumbar spine (LS) was performed at study entry (baseline, BL) and after 96 weeks. Percentage BMD change from BL was evaluated using a general linear model, including factors potentially associated with bone loss. Results One hundred and sixty PLWH were enrolled (26.3% female, mean age 49.9 ± 11.2 years) from April 2015 to April 2017. Overall, we could calculate BMD change from baseline, for at least one site, in 133 subjects (83.1%). After a median of 102 weeks (IQR: 90-110), mean FN BMD increased, but not significantly, whereas LS BMD showed a significant mean increase of 13.1 (95% confidence interval, CI: 1.7-24.6) mg/cm3 (+1.6%, 95% CI: 0.3%, 2.8%) after a median time of 102 weeks (IQR: 84-110). As regards LS BMD, patients with osteopenia/osteoporosis at study entry experienced a high increase from baseline (20.6, 95% CI: 3.1, 38.1 mg/cm3), as well as experienced subjects (16.9, 95% CI: 4.7, 29.2 mg/cm3) and those on vitamin D supplementation (26.8, 95% CI: 7.7, 45.9 mg/cm3). Conclusion Dolutegravir-containing regimens could reduce the negative impact of antiretroviral therapy on bone, especially in patients with low BMD.

OBJECTIVE Assessment of the feasibility and effectiveness of a brief intervention for smoking cessation in people living with HIV (PLWH). SETTING Multicenter cohort prospective study involving PLWH from 10 Italian infectious disease centers. METHODS During routine HIV care, clinicians delivered the 5As brief intervention (Ask, Advise, Assess, Assist, Arrange) to each patient who enrolled in the study, following the European AIDS Clinical Society guidelines. At study end, participating clinicians evaluated their own adherence to intervention: "standard" if counseling was delivered in at least half of the follow-up visits, "soft" if less. The main outcome measure was smoking abstinence ≥6 months. Abstinence predictors were evaluated using a Cox-proportional hazard regression model. RESULTS One thousand eighty-seven PLWH-patients (age 47.9 ± 10.8, male 73.5%) were followed for a median of 23 months (interquartile range 21-25). At baseline, current smokers were 561 (51.6%). Standard intervention was performed in 4 of 10 centers and included 343 smokers; soft intervention was performed in 6 centers (218 smokers). At last visit, 35 patients in standard (10.8%) and 6 in soft intervention (2.8%) achieved self-reported tobacco abstinence ≥6 months (P = 0.0009). Overall, the 5As intervention led to 7.3% 6-month interruptions. In the multivariable analysis, significant predictors for 6-month smoking cessation were: lower Fagerstrom score, stage of change (preparation/contemplation vs. precontemplation), and standard intervention. CONCLUSION Adherence to the 5As brief intervention emerged as a critical factor for success. In fact, compared with soft intervention, the standard intervention significantly increased abstinence, highlighting that clinicians need more time and supporting tools to encourage PLWH to quit smoking.

Objective: This prospective, multicenter, non-interventional cohort study enrolling human immunodeficiency virus (HIV)-1-infected, virally suppressed adult outpatients in Italy aimed to describe results obtained from patient-reported outcome questionnaires regarding treatment satisfaction and symptom perceptions in HIV-1-positive patients who switched to cobicistat-boosted darunavir antiretroviral regimens, coming from ritonavir-boosted protease inhibitors. Methods: Patients entered this study between June 2016 and February 2017, once their treating physician had considered them eligible for cobicistat-boosted darunavir-based treatment as per clinical practice. Patients’ satisfaction regarding regimen and current symptom burdens were assessed using two previously validated, patient-reported outcome questionnaires: HIV Treatment Satisfaction Questionnaire (HIV-TSQ) and HIV Symptoms Distress Module (HIV-SDM). These questionnaires were administered at prespecified time-points: enrollment (Visit 1), 4–8weeks later (Visit 2), and 48 ± 6weeks after study enrollment (Visit 4). Data of patient-reported outcome total scores for both questionnaires are presented as median with 25th–75th percentiles. Questionnaires scores were analyzed overall and stratified by gender when applicable. A p value of less than 0.05 was considered statistically significant. A sensitivity analysis was conducted to evaluate the role of lost to follow-up, using the “last observation carried forward” method. Results: A total of 348 patients were enrolled in this study; 296 patients (208 male and 88 female) provided both evaluable HIV-TSQ and HIV-SDM at enrollment and at 4–8weeks, while 250 patients (174 male and 76 female) provided questionnaire data at enrollment and at 48 ± 6weeks. The total scores of HIV-TSQ showed improvements in patient satisfaction in the overall population both at Visit 2 and Visit 4 (p < 0.001, sign test) and also when stratified by gender throughout the study period. In addition, the overall burden of symptoms, as shown by the HIV-SDM scores, decreased. Conclusions: Switching to a cobicistat-boosted darunavir-based therapy led to overall increased patient satisfaction and reduced symptom burden when compared with previous regimens. The use of patient-reported outcomes in clinical daily practice could provide a useful tool towards achieving guideline goals to achieve “fourth 90”, having 90% of virally suppressed patients with a good health-related quality of life.

Objective: This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated. Setting: Prospective, multicenter, single-country, noninterventional cohort study. Methods: This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA

Background: Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are lacking. Aim: To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD). Methods: All HCV patients treated with DAA in Lombardy (December 2014–November 2017) with available kidney function tests during and off-treatment were included. Results: Among 3264 patients [65% males, 67% cirrhotics, eGFR 88 (9–264) ml/min], CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33–45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively). Conclusions: During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.

Nelle persone che vivono con HIV (PLWH), il peso delle patologie corniche non trasmissibili è aumentato nel tempo, a causa dell’invecchiamento legato a una maggiore sopravvivenza, all’infiammazione cronica, all’attivazione del sistema immunitario, e all’esposizione a lungo termine alla terapia antiretrovirale (ART). L’età anagrafica, quella alla diagnosi di infezione da HIV, e l’esposizione alla ART sono fattori che possono esercitare un effetto sulle differenze sia qualitative che quantitative tra le comorbidità.Per esplorare questa ipotesi, abbiamo valutato la prevalenza di alcune patologie selezionate nei pazienti arruolati nel progetto SCOLTA, per gruppi di età (50-59 e ≥60 anni) e durata della ART. In 1336 soggetti (23.9% donne), la durata della ART era simile tra gruppi di età, sia considerata in continuo (p=0.85) che in categorie (p=0.88). Come atteso, le comorbidità e la multimorbidità erano meno frequenti nel gruppo 50-59 che in quello ≥60 anni. Gli odds ratios (ORs) aggiustati per sesso ed età hanno mostrato che, nella categoria 50-59, si rilevava un aumento di rischio significativo e coerente in categorie di durata della ART, per le malattie cardiovascolari (CVD) (ORs da 1.68 a 2.18), dislipidemia (ORs da 3.61 a 9.08) e osteopenia/osteoporosi (ORs da 3.74 a 6.23). Di conseguenza, anche il rischio di multimorbidità aumentava attraverso le classi di durata della ART (ORs da 2.04 a 4.40). Nel gruppo ≥60 anni, il rischio CVD era significativamente più elevato solo nei pazienti con durata della ART ≥20 anni (OR 2.61, 95% intervallo di confidenza al 95% 1.22-5.58, categoria di riferimento ≤6 mesi). L’aumento di dislipidemia e multimorbidità era coerentemente associato con una maggiore durata della ART.In conclusione, l’età anagrafica, quella alla diagnosi di infezione da HIV, e l’esposizione alla ART sono associate alla multi-morbidità nelle PLWH.

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n=748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2, 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P&nbsp

Background Among people living with HIV (PLWH), the prevalence of non-HIV related co-morbidities is increasing. Aim of the present study is to describe co-morbidity and multi-morbidity, their clustering mode and the potential disease-disease interactions in a cohort of Italian HIV patients. Methods Cross-sectional analysis conducted by the Coordinamento Italiano per lo Studio di Allergia e Infezioni da HIV (CISAI) on adult subjects attending HIV-outpatient facilities. Non-HIV co-morbidities included: cardiovascular disease, diabetes mellitus, hypertension, oncologic diseases, osteoporosis, probable case of chronic obstructive pulmonary disease (COPD), hepatitis C virus (HCV) infection, psychiatric illness, kidney disease. Multi-morbidity was defined as the presence of two or more co-morbidities. Results One thousand and eighty-seven patients were enrolled in the study (mean age 47.9 ± 10.8). One hundred-ninety patients (17.5%) had no co-morbidity, whereas 285 (26.2%) had one condition and 612 (56.3%) were multi-morbid. The most recurrent associations were: 1) dyslipidemia + hypertension (237, 21.8%); 2) dyslipidemia + COPD (188, 17.3%); 3) COPD + HCV-Ab+ (141, 12.9%). Multi-morbidity was associated with older age, higher body mass index, current and former smoking, CDC stage C and longer ART duration. Conclusions More than 50% of PLHW were multi-morbid and about 30% had three or more concurrent comorbidities. The identification of common patterns of comorbidities address the combined risks of multiple drug and disease-disease interactions.

Questo studio analizza i ricoveri ospedalieri e l’outcome di 80 pazienti HIV-positivi, con diagnosi di infezione da SARS-CoV-2 effettuata tra febbraio e settembre 2020, in una rete di centri di Malattie Infettive italiani. Sesso, etnia e durata dell’infezione da HIV e dei trattamenti antiretrovirali (ART) erano simili nei soggetti ricoverati e non, mentre i 45 pazienti ricoverati erano più vecchi, avevano valori più bassi sia per quanto riguarda il nadir dei CD4 che la conta dei linfociti al momento della diagnosi. Questi due valori erano anche correlati ad un esito peggiore della COVID-19. Durante il periodo di osservazione, 10 (12.3%) pazienti sono morti. La terapia ART non sembrava associata con la severità della malattia da SARS-CoV-2. This study reports on hospital admission and outcomes of 80 HIV-infected subjects who were diagnosed with SARSCoV-2 infection between February and September 2020, in a network of Italian centers. Sex, ethnicity and duration of HIV infection and antiretroviral therapy (ART) were similar in admitted and non-admitted subjects, whereas 45 admitted patients were older, had lower nadir CD4 cells and current lymphocytes count. These values were also correlated to worse COVID-19 outcome. Ten (12.3%) patients died over the observation period. ART drugs did not seem associated with disease severity.

This study evaluates the frequency and causes of dolutegravir (DTG) discontinuation along 5 years of follow-up, in both antiretroviral treatment (ART)-naive and experienced people living with HIV (PLWH). This is a prospective multi-center cohort study enrolling PLWH on DTG from July 2014 until November 2020. DTG-durability was investigated using the Kaplan-Meier survival curve. The Cox proportional-hazards model was used for estimating the hazard ratio (HR) of DTG discontinuation for any cause, and for adverse events (AEs). Nine hundred sixty-three PLWH were included, 25.3% were women and 28.0% were ART-naive. Discontinuations for any causes were 10.1 [95% confidence interval (95% CI) 8.9-11.5] per 100 person-years, similar in most regimens, with the apparent exception of tenofovir alafenamide/emtricitabine+DTG (p

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: 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.

Objective This prospective, multicenter, non-interventional cohort study enrolling human immunodeficiency virus (HIV)-1-infected, virally suppressed adult outpatients in Italy aimed to describe results obtained from patient-reported outcome questionnaires regarding treatment satisfaction and symptom perceptions in HIV-1-positive patients who switched to cobicistat-boosted darunavir antiretroviral regimens, coming from ritonavir-boosted protease inhibitors. Methods Patients entered this study between June 2016 and February 2017, once their treating physician had considered them eligible for cobicistat-boosted darunavir-based treatment as per clinical practice. Patients’ satisfaction regarding regimen and current symptom burdens were assessed using two previously validated, patient-reported outcome questionnaires: HIV Treatment Satisfaction Questionnaire (HIV-TSQ) and HIV Symptoms Distress Module (HIV-SDM). These questionnaires were administered at prespecified time-points: enrollment (Visit 1), 4–8 weeks later (Visit 2), and 48 ± 6 weeks after study enrollment (Visit 4). Data of patient-reported outcome total scores for both questionnaires are presented as median with 25th–75th percentiles. Questionnaires scores were analyzed overall and stratified by gender when applicable. A p value of less than 0.05 was considered statistically significant. A sensitivity analysis was conducted to evaluate the role of lost to follow-up, using the “last observation carried forward” method. Results A total of 348 patients were enrolled in this study; 296 patients (208 male and 88 female) provided both evaluable HIV-TSQ and HIV-SDM at enrollment and at 4–8 weeks, while 250 patients (174 male and 76 female) provided questionnaire data at enrollment and at 48 ± 6 weeks. The total scores of HIV-TSQ showed improvements in patient satisfaction in the overall population both at Visit 2 and Visit 4 (p

BackgroundAn unexpected excess in weight gain has recently been reported in the course of dolutegravir (DTG) treatment. The aim of the present study was to investigate whether weight gain differs among different DTG-containing regimens.MethodsAdult naïve and experienced people with HIV (PWH) initiating DTG-based antiretroviral therapy (ART) between July 2014 and December 2019 in the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) prospective cohort were included. We used an adjusted general linear model to compare weight change among backbone groups and a Cox proportional hazard regression model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for weight increases >10% from baseline.ResultsA total of 713 participants, 25.3% women and 91% Caucasian, were included. Of these, 195 (27.4%) started DTG as their first ART regimen, whereas 518 (72.6%) were ART-experienced. DTG was associated with abacavir/lamivudine in 326 participants, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 148, boosted protease inhibitors in 60, rilpivirine in 45, lamivudine in 75, and tenofovir alafenamide (TAF)/FTC in 59. At 6 and 12 months, weight gain was highest among PWH on TDF/FTC+DTG and TAF/FTC+DTG. Baseline CD4 10% from baseline. Higher weight (HR, 0.97 by 1 kg; 95% CI, 0.96 to 0.99) and female gender (HR, 0.54; 95% CI, 0.33 to 0.88) were protective against weight gain.ConclusionsNaïve PWH with lower CD4 counts and those on TAF/FTC or TDF/FTC backbones were at higher risk of weight increase in the course of DTG-based ART.

In a nationwide Italian sample of people living with HIV (PLWH), the prevalence of smoking, nicotine dependence, propensity to stop smoking, and cardiovascular profile were investigated. The nicotine dependence by Fagerström test and the propensity to stop according to the stages of change were evaluated. Associations between smoking habits and patients' characteristics were analyzed using an unconditional logistic regression model. Among 1,087 PLWH (age 47.9 ± 10.8 years, men 73.5%), the prevalence of current smokers was 51.6%. The median of Fagerström test was 4 (interquartile range 2-6); 60.1% of the smokers were in precontemplation, 17.6% in contemplation, 18.7% in preparation, and 3.6% in action. In a logistic multivariate model, current smoking was associated with male sex, being divorced/widowed, Caucasian ethnicity, dyslipidemia, atherosclerotic cardiovascular disease risk, psychiatric comorbidity, hepatitis C virus infection, and alcohol abuse. Low high-density lipoprotein cholesterol level was associated with high nicotine dependence. More than 50% of PLWH were current smokers, one-third of them showed a high or very high degree of dependence. Our findings draw attention to the need of smoking cessation strategies for PLWH.

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 12weeks 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 Log10HCV-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.

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 vs 90.7% OTA (p=0.003) and 46.3% ABSSSI vs 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 (13.5days, 5.5–22 vs 3, 0–11.7; p80%, 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.

This is a multicenter cross-sectional study where we aimed to detect the rate of osteopenia/osteoporosis in an HIV female population (WLWHIV) by means of "heel quantitative ultrasound" (QUS) measurement. We enrolled 273 patients, mean age 48.1 years, 36% menopausal, 96% on combination antiretroviral therapy (cART). Calcaneal measure of bone mass index by QUS revealed osteopenia and osteoporosis in 76 (27.8%) and 16 (5.9%) WLWHIV. Our data underline the correlation between low QUS parameters and traditional risk factors for osteoporosis rather than with cART exposure, thus suggesting the crucial importance of detection and correction of traditional risk factors for osteoporosis in WLWHIV.

Paola Bagella,1 Nicola Squillace,2 Elena Ricci,3 Roberto Gulminetti,4 Giuseppe Vittorio De Socio,5 Lucia Taramasso,6 Giovanni Pellicanò,7 Barbara Menzaghi,8 Benedetto Maurizio Celesia,9 Chiara Dentone,10 Giancarlo Orofino,11 Paolo Bonfanti,12 Giordano Madeddu13On behalf of the C.I.S.A.I. Study Group, Italy1Unit of Post-acute Long Term Care, ATS Sardegna, Sassari, Italy; 2Infectious Diseases Unit, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy; 3Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy; 4Unit of Infectious Diseases, IRCCS San Matteo Hospital, Pavia, Italy; 5Infectious Diseases Unit Department of Medicine, Azienda Ospedaliero-Universitaria di Perugia, Santa Maria Hospital, Perugia, Italy; 6Infectious Diseases Unit, Department of Internal Medicine, Fondazione IRCCS Ca‘ Granda Ospedale Maggiore Policlinico, Milan, Italy; 7Department of Human Pathology of the Adult and the Developmental Age ‘G. Barresi‘, Unit of Infectious Diseases, University of Messina, Messina, Italy; 8Unit of Infectious Diseases, ASST della Valle Olona, Busto Arsizio, Italy; 9Unit of Infectious Diseases, Garibaldi Hospital, Catania, Italy; 10Unit of Infectious Diseases, Sanremo Hospital, Sanremo, Italy; 11Unit of Infectious Diseases, Amedeo di Savoia Hospital, Turin, Italy; 12Unit of Infectious Diseases, A. Manzoni Hospital, Lecco, Italy; 13Unit of Infectious Diseases, Department of Clinical, Surgical and Experimental Medicine, University of Sassari, Sassari, ItalyIntroduction: 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.Keywords: HIV-1 infection, dolutegravir/abacavir/lamivudine, lipid profile

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

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&ndash, 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&rsquo, 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, p-value: 0.016) and social costs (FTC/TDF: &minus, 0.23, FTC/TAF: 1.04, ABC/3TC: 0.23, p-value &lt, 0.001), improving patient quality of life (FTC/TDF: 0.31, FTC/TAF: 1.85, ABC/3TC: 0.38, 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.

Background The advent of new HCV drugs has generated widespread economic concerns, particularly within the Italian setting, characterized by continuous linear cuts and spending review actions. The overall trade-off between investments and savings needs an in depth analysis. Aims The study aimed to estimate the budget impact of the introduction of the novel drugs approved during the year 2015, compared with the historical situation based on the different treatment options available prior to 2015. Methods A three-year budget impact model was developed, taking into consideration the Lombardy Region (Northern Italy) Health Service perspective. The degree of liver fibrosis, genotypes, presence of only HCV or HIV/HCV co-infections, presence or absence of sustained virological response, and direct healthcare total costs were the variables of the model. Results With the introduction of the novel regimens, a higher number of HCV patients achieved a sustained virological response (+20%). Further analysis showed that an investment in innovative technologies would have given the Regional System significant economic savings within the 36-month period (−6.64%/−7.15%). Conclusions Treating HCV-infected persons in the Lombardy Region with the new drugs would reduce healthcare expenditure on this specific disease, in each forecast implemented, thus reducing the economic burden of the pathology.

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.