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Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load < 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (−0.36, p < 0.0001) than in the RPV cohort (−0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT > 40 IU/L experienced a significant decline (−14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

Introduction Integrase strand transfer inhibitors (INSTI) are one of the most prescribed drug classes for the treatment of HIV infection worldwide. Emtricitabine/Tenofovir Alafenamide/ Bictegravir (FTC/TAF/BIC) has been evaluated in randomized clinical trials; few studies have verified tolerability and safety in clinical practice. Our aim was to investigate the metabolic and hepatic safety in a real-life setting of FTC/TAF/BIC. Materials and methods Consecutive people living with HIV infection (PLWH) enrolled in the SCOLTA project, switching to or initiating their first antiretroviral treatment with FTC/TAF/BIC were included. PLWH with HBV co-infection were excluded. Metabolic and hepatic variables were collected at T0 and T1, were defined as baseline and 6-month follow-up respectively, and their modifications were analysed using the paired t-test and the analysis of variance. Results Five hundred and thirty-nine PLWH with at least one follow-up visit were included in the analysis. Mean age was 48 years (±12.1), 74% were male, 16.1% were naïve to antiretrovirals (ART). At T1, ART-experienced PLWH showed a significant reduction of total cholesterol (TC) and triglycerides, and a slight increase in blood glucose (BG) and ALT. On the contrary, in ART-naïve PLWH blood lipids significantly increased, although with an unaffected TC/high density lipoprotein (HDL)-c ratio, while alanine aminotransferase (ALT) decreased significantly, mainly in those with altered baseline level. The treatment interruptions were 45 (8.4%) over the whole observation period, 13 (2.4%) due to AEs. The most frequent AEs were related to the central nervous system (6 events of depression, insomnia, headache, agitation) and 3 PLWH discontinued the regimen because of grade 1-2 weight gain. Conclusions In ART-experienced PLWH switching to FTC/TAF/BIC a significant improvement of lipid profile occurred but with significant BG and ALT variation without clinical relevance. In ARTnaïve PLWH, blood lipid

Background: Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. Methods: We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. Results: In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. Conclusions: PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, w

In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients’ decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions.

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.

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 Fagerström 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.

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naïve to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19–0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts.

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.

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-RNA < 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.

Objectives: The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross-sectional studies conducted over three different periods: 2005, 2011 and 2015. Methods: This was a multi-centre, nationwide study. Data were collected in three studies from the CISAI group – SIMOne, HIV-HY and STOPSHIV – and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. Results: Overall, the mean age was 46.9 ± 10.2 years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52–0.78) in 2011 and 0.56 (95% CI: 0.46–0.69) in 2015 compared with 2005, while BMI (kg/m2) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p < 0.0001). Conclusions: In recent years, PHIV have had a significantly improved metabolic profile compared with previously, despite increasing weight and BMI.

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.

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.

Background: Psychological factors (PFs) are known predictors of cardiovascular disease (CVD) in many clinical settings, but data are lacking for human immunodeficiency virus (HIV) infection. We carried out a prospective study to evaluate (1) psychological predictors of preclinical and clinical vascular disease and (2) all-cause mortality (ACM) in HIV patients. Methods: We conducted a cross-sectional analysis of baseline data to evaluate the predictors of carotid plaques (CPs) and a prospective analysis to explore predictors of vascular events (VEs) and ACM over 10 years. Human immunodeficiency virus patients monitored at the Infectious Disease Units of 6 Italian regions were consecutively enrolled. Traditional CVD risk factors, PFs (depressive symptoms, alexithymia, distress personality), and CPs were investigated. Vascular events and ACM after enrollment were censored at March 2018. Results: A multicenter cohort of 712 HIV-positive patients (75.3% males, aged 46.1 ± 10.1 years) was recruited. One hundred seventy-five (31.6%) patients had CPs at baseline. At the cross-sectional analysis, alexithymia was independently associated with CPs (odds ratio, 4.93; 95% confidence interval [CI], 2.90-8.50; P <. 001), after adjustment for sociodemographic, clinical, and psychological variables. After an average follow-up of 4.4 ± 2.4 years, 54 (7.6%) patients developed a VE, whereas 41 (5.68%) died. Age, current smoking, hypertension, and alexithymia (hazard ratio [HR], 3.66; 95% CI, 1.80-7.44; P <. 001) were independent predictors of VE. Likewise, alexithymia was an independent predictor of ACM (HR, 3.93; 95% CI, 1.65-9.0; P =. 002), regardless of other clinical predictors. Conclusions: The present results validate our previous monocentric finding. Alexithymia may be an additional tool for the multifactorial assessment of cardiovascular risk in HIV.

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, setting, and participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main outcomes and measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce t

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 < 0.0001). In the multivariable Cox regression model, non-Caucasian ethnicity, age ≥50 years, and lower estimated glomerular filtration rate (eGFR) were associated with a higher probability of DTG interruption. The incidence rate of virological failure was 0.4 (95% CI 0.2-0.7) per 100 person-years, while the estimated discontinuation rate for AEs was 4.0 (3.2-4.9) per 100 person-years. Thirty-four DTG interruptions were due to grade ≥3 events (10 central nervous system, 6 hypersensitivity, 3 renal, 3 myalgia/asthenia, 3 abdominal pain, 2 gastrointestinal, and 7 other events). People with lower body mass index, age ≥50 years, and lower eGFR were at higher risk of AEs, while dual combinations were protective (HR 0.41 compared with abacavir/lamivudine/DTG, 95% CI 0.22-0.77). In this prospective observational study, we found high DTG durability and a low rate of virological failures. Dual therapies seemed protective toward AEs and might be considered, when feasible, a suitable option to minimize drug interactions and improve tolerability.

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 (±10.1). 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.

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.

Background: Tobacco use is a leading cause of preventable diseases and death for all individuals, even more so for people living with HIV (PLWH), due to their status of chronic inflammation. To date, in Italy no study was performed to compare smoking habits in PLWH and the general population. We aimed to investigate smoking habits in PLWH, as compared to the general population. Methods: Multi-center cross-sectional study. Smoking habits were compared between PLWH and the general population. PLWH were enrolled in the STOPSHIV Study. The comparison group from the general population was derived from a survey performed by the National Statistics Institute (ISTAT), with a stratified random sampling procedure matching 2:1 general population subjects with PLWH by age class, sex, and macro-area of residence. Results: The total sample consisted of 1087 PLWH (age 47.9 ± 10.8 years, male 73.5%) and 2218 comparable subjects from the general population. Prevalence of current smokers was 51.6% vs 25.9% (p < 0.001); quitting smoking rate was 27.1% vs. 50.1% (p < 0.001) and the mean number of cigarettes smoked per day was 15.8 vs. 11.9 (p < 0.001), respectively for PLWH and the general population. Smoking and heavy smoking rates amongst PLWH were significantly higher even in subjects who reported diabetes, hypertension and extreme obesity (p < 0.001). Logistic regressions showed that PLWH were more likely current smokers (adjusted Odds Ratio, aOR = 3.11; 95% Confidence Interval (CI) =2.62–3.71; p < 0.001) and heavy smokers (> 20 cigarettes per day) (aOR = 4.84; 95% CI = 3.74–6.27; p < 0.001). PLWH were less likely to have quitted smoking (aOR = 0.36; 95% CI = 0.29–0.46; p < 0.001). Conclusion: HIV-infected patients showed a higher rate of current smokers, a larger number of cigarettes smoked and a lower quitting rate than the general population. Our findings emphasize the need for smoking cessation strategies targeting HIV persons.

Background An 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. Methods Adult 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. Results A 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 <200 cells/mm3 (HR, 1.84; 95% CI, 1.15 to 2.96), being ART-naïve (HR, 2.24; 95% CI, 1.24 to 4.18), and treatment with TDF/FTC+DTG (HR, 1.92; 95% CI, 1.23 to 2.98) or TAF/FTC+DTG (HR, 3.80; 95% CI, 1.75 to 8.23) were associated with weight gain >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. Conclusions Naïve 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.

Objectives: The study aim was to evaluate the impact on Liver and Kidney toxicity of the single tablet regimen Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (EVG/COBI/ FTC/TDF) on Antiretroviral Therapy (ART) experienced or naïve patients. Methods: Patients initiating EVG/COBI/FTC/TDF were enrolled in the SCOLTA project, a multicenter observational study reporting grade 3–4 Adverse Events in subjects beginning new antiretroviral drug regimens. In this analysis, patients were evaluated at T0 (baseline), T1 (six months) and at T2 (twelve months). Results: A total of 329 patients were enrolled, and 280 (85.1%) of these had at least one follow-up visit. Median observation time was 11 months (IQR 7.0–15.5). Two hundred and two patients (72.1%) were ART experienced and 78 (27.9%) ART naive. Prevalence of HCV-coinfection was 21.4%. At T1, we observed a significant decline in estimated glomerular filtration rate (eGFR), both in experienced and naive patients (mean change from T0–7.5 ± 12.8 ml/min, -15.5 ± 17.8 ml/min, respectively, p = 0.0005), which was confirmed at T2 (mean change from T0–8.2 ± 15.8 ml/min, -17.6 ± 19.4 ml/min, respectively, p = 0.001). Regarding aspartate aminotransferase (AST) and alanine transaminase (ALT) grade 1–2 modifications, no significant differences were observed between experienced and naïve subjects, but an increased prevalence of abnormal liver function test was observed in patients with chronic HCV infection (p<0.001). Conclusions: A significant decline in eGFR was observed in patients initiating EVG/COBI/FTC/TDF in the first 6 months, with no significant worsening occurring at 12 months vs. 6 months of therapy. Patients with chronic HCV infection were at higher risk to develop abnormal liver tests.

Weight gain and body mass index (BMI) increase are central issues in patients living with HIV who need to minimize the risk of metabolic disease. Information collected through the SCOLTA cohort revealed significant 1-year BMI increase in patients treated with dolutegravir (P = .004), raltegravir (P = .0004), elvitegravir (P = .004), darunavir (P = .0006), and rilpivirine (P = .029). BMI gain correlated with low baseline BMI (P = .002) and older age (P = .0007) in Centers for Disease Control and Prevention stages A/B, with lower BMI (P = .005) and CD4+ T-cell count (P = .007) at enrollment in stage C.

Background: Hypertension control is often inadequate in HIV patients. In a contemporary, nationwide cohort of Italian HIV-infected adults, we assessed time trends in hypertension prevalence, awareness, treatment, and control. We also evaluated predictors of cardiovascular events and of new-onset hypertension. Methods: Multicenter prospective cohort study, sampling 961 consecutive HIV patients (71% men, mean age 46 ± 9 years, 30% hypertensive) examined in 2010-2014 and after a median follow-up of 3.4 years. Results: Among hypertensive patients, hypertension awareness (63% at baseline and 92% at follow-up), treatment (54 vs. 79%), and control (35 vs. 59%) all improved during follow-up. The incidence of new-onset hypertension was 50.1/1000 person-years (95% confidence interval, 41.2-60.3). Multivariable-adjusted predictors of hypertension were age, BMI, estimated cardiovascular risk, blood pressure, and advanced HIV clinical stage. In total, 35 new cardiovascular events were reported during follow-up (11.1/1000 person-years). In a multivariate model, baseline cardiovascular risk and hypertensive status predicted incident cardiovascular events, whereas a higher CD4 cell count had a protective role. In treated hypertensive patients, the use of integrase strand transfer inhibitors at follow-up was associated with a lower SBP (average yearly change,-3.8 ± 1.6 vs.-0.9 ± 0.5 mmHg in integrase strand transfer inhibitor users vs. nonusers, respectively, P = 0.02). Conclusion: Hypertension awareness, treatment, and control rates all improved in adult Italian HIV patients over the last few years, although hypertension remains highly prevalent (41%) in middle-aged HIV patients, and significantly impacts cardiovascular morbidity. Traditional risk factors and advanced HIV disease predict new-onset hypertension, whereas CD4 cell count favorably affects future cardiovascular events.

The aim of the study is to propose a multidimensional second-level diagnostic assessment to allow follow- up in the event physicians observe the presence of risk factors and/or active co-morbidities in HIV-infected patients. To develop our proposal, we chose the Delphi method that has been used for about 30 years in the healthcare field. The CISAI Group (Coordinamento Italiano per lo Studio dell'Allergia in Infezione da HIV) conducted this study. The first phase of the study provided identification of the questionnaire for second-level diagnostic assessment of HIV-infected patients. From March to July 2018 the questionnaire was submitted to 48 experts from 10 Italian HIV-dedicated sites. The questionnaire consisted of 102 items divided into 7 survey areas. The results can be summarized as follows: infectious disease diagnostics, 18 items reached agreement in 9 cases; osteoporosis diagnostics 12 items with 3 agreements; metabolic and cardiovascular diagnostics 13 items with 4 agreements; nephrology diagnostics 19 items with 8 agreements; hepatology diagnostics 12 items with 9 agreements; CNS diagnostics: 18 items with 7 agreements; psychological diagnostics and quality of life assessment (QoL) 10 items with no agreement. If these considerations are confirmed in required discussions and in-depth analyses, they will be able to produce an important indication in the drafting of national guidelines.

Introduction: 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.

We evaluated the efficacy and safety of a two-drug regimen including dolutegravir (DTG) and unboosted atazanavir (uATV) in 151 HIV-1 infected patients with HIV-RNA of more than 50 copies/ml. During a median follow-up of 62 (42-97) weeks, two virological failures (1%) and 13 treatment discontinuations (9%) occurred; the 48-week probability of virological failure was 0.8% (95% confidence interval 0.2-5.6%). Switch to DTG + uATV may represent a boosting and transcriptase reverse inhibitors sparing otion in individuals with long exposure to antiretroviral therapy and risk of cardiovascular disease.

Objectives: To investigate the use of statins and acetylsalicylic acid (ASA) in HIV people in clinical practice. Design: A multicenter, nationwide, prospective cohort study, including 1182 consecutive HIV patients was conducted. Methods: Statin and ASA prescription was evaluated in primary and secondary cardiovascular disease prevention, according to the European AIDS Clinical Society (EACS) guidelines. Results: Followed-up patients (998) were mostly males (70.9 %) with a mean age at enrolment of 46.5 years (SD 9.5). The mean time of follow-up was 3.3 years (SD 0.8). At the last follow-up visit, statins would have been recommended for 31.2 % and ASA for 16 % by EACS guidelines. Conversely, only 15.6 and 7.6 % of patients were on statin and ASA treatment, respectively; only 50.3 % of patients treated with statins achieved recommended low-density lipoprotein cholesterol (LDL-c) levels. At the last follow-up visit, agreement between statin therapy and EACS recommendation was 0.58 (95 % CI 0.52–0.63). The corresponding figure for ASA therapy was 0.50 (95 % CI 0.42–0.58), whereas the agreement for ASA therapy in secondary prevention was 0.59 (95 % CI 0.50–0.68). Conclusions: The prescription of statins and ASA in HIV-infected patients remains largely suboptimal, as only about 50 % of patients requiring statins and ASA are properly treated. Higher attention on this relevant issue and further investigation are warranted in this at risk population.