Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Evaluation of Myo-Intimal Media Thickness and Atheromatous Plaques in People Living with HIV from the Archiprevaleat Cohort vs. HIV-Negative Subjects.

BACKGROUND: Antiretroviral therapy has allowed a clear improvement in prognosis for HIV patients, but metabolic problems, such as dyslipidemia, remain. This can lead to the development of atheromatous plaques. Our study aims to evaluate whether HIV-positive (HIV+) patients show higher myo-intimal media thickness (IMT) and atheromatous plaques compared to HIV-negative (HIV-) patients. METHODS: To evaluate the association between HIV infection in experienced patients and vascular pathology, we performed a cross-sectional study, observing 1006 patients, 380 HIV+ enrolled in the Archiprevaleat cohort, and 626 HIV- as a control group. All patients underwent a Doppler scan of the supra-aortic vessels. We compared the prevalence of IMT > 1.0 mm and plaques in the two groups. RESULTS: Patients in the HIV+ group were younger than those in the HIV- group, with a lower prevalence of hypertension and diabetes and higher dyslipidemia. The prevalence of plaques in strata of age was higher in the HIV+ group than in the HIV- group and was associated with the length of ART exposure. CONCLUSIONS: Our cross-sectional, retrospective study shows that HIV+ experienced patients are at greater risk of IMT and atheromatous plaques compared to HIV-. The risk is associated with being HIV+ and with the length of ART exposure. This finding may be useful in preventing cardiovascular risk.

Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study.

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.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centered approach. Consensus Guidance Using a Delphi Process.

Definitive data on the long-term success of the latest antiretroviral therapy (ART) strategies are still lacking. A panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow ART over time. Panelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Ninety infectious diseases specialists from several Infectious Diseases Centers in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long-term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need for an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality-of-life monitoring during the standard follow up of people living with HIV. The consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.

Clinical and epidemiological factors causing longer SARS-CoV 2 viral shedding: the results from the CoviCamp cohort.

INTRODUCTION: The aim of this study was to investigate how long hospitalized patients stayed positive to the nasopharyngeal swab, and what demographic and clinical factors influence the time-to-negative swab. METHODS: We enrolled in a multicenter, observational, retrospective study involving 17 COVID-19 units in eight cities of the Campania, southern Italy all patients hospitalized from March 2020 to May 2021 diagnosed with Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-CoV-2) infection for whom time-to-negative swab was available. RESULTS: 963 patients were enrolled. We defined three groups considering time-to-negative swab: the first including patients with time-to-negative swab before the 26th day, the second including patients with time-to-negative swab from day 26 to day 39, and the third including patients with time-to-negative swab > 39 days. 721 (74.9%) patients belonged to the first group, 194 (20.1%) to the second, and 52 (5.4%) belonged to the third group. Belonging to group 2 and 3 seemed to be influenced by age (p value < 0.001), Charlson comorbidity index (p = 0.009), arterial hypertension (p = 0.02), cardiovascular disease (p = 0.017), or chronic kidney disease (CKD) (p = 0.001). The multivariable analysis confers a leading role to CKD, with an odds ratio of 2.3 as factor influencing belonging to the groups showing a longer time-to-negative swab. Patients with CKD and diabetes were more frequently in the third group. DISCUSSION: Our analysis showed that CKD is a factor related to longer time-to-negative swab, probably because of immunosuppression related to this condition.

A multidisciplinary dermatology-gastroenterology-rheumatology (DER.RE.GA) unit for the care of patients with immune-mediated inflammatory diseases: analysis of the first 5 years from the dermatologist's perspective.

Immune-mediated inflammatory diseases (IMIDs) constitute a heterogenous group of chronic and highly disabling conditions. The clinical challenges they often pose led to formation of numerous dermo-rheumatological interdisciplinary units around the world, which are reported to benefit their patients in various ways. The present paper describes our experience with a multidisciplinary dermatology-rheumatology-gastroenterology unit DERREGA at the IRCCS Foundation Policlinico San Matteo of Pavia over a period of 5 years of its activity (2017-2022). A digital database was created, containing the medical records of 146 patients referred to the dermatology unit only by rheumatologists or gastroenterologists belonging to the multidisciplinary unit DERREGA. Then, aspects such as demographics, initial basis of referral and final diagnosis among the patients were analyzed retrospectively. Patients were classified as either gastroenterological or rheumatological, and then categorized according to the specific basis of referral. Most of the gastroenterological patients (97%) were affected by inflammatory bowel diseases (IBDs). Rheumatological patients were divided in three subgroups, including patients referred with vasculitis, arthropathies (undifferentiated arthritis, psoriatic arthritis and other arthritis) and other rheumatological diseases. Then, final diagnoses were evaluated in each group. Almost a third of IBD patients received a diagnosis of paradoxical psoriasis. Dermatological examination allowed diagnosis of minimal psoriasis based on Caspar criteria in over 70% of the patients admitted with undifferentiated arthritis. A multidisciplinary approach is suggested to provide more effective management of IMIDs and, specifically, from a dermatological perspective, allows for the diagnosis of minimal manifestations of psoriasis in patients with a provisional diagnosis of undifferentiated arthritis.

Prognostic Value of Creatinine Levels at Admission on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study.

INTRODUCTION: Acute kidney disease and chronic kidney disease are considered conditions that can increase the mortality and severity of COVID-19. However, few studies have investigated the impact of creatinine levels on COVID-19 progression in patients without a history of chronic kidney disease. The aim of the study was to assess the impact of creatinine levels at hospital admission on COVID-19 progression and mortality. METHODS: We performed a multicenter, observational, retrospective study involving seventeen COVID-19 Units in the Campania region in southern Italy. All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction on a naso-oropharyngeal swab, from 28 February 2020 to 31 May 2021, were enrolled in the CoviCamp cohort. RESULTS: Evaluating inclusion/exclusion criteria, 1357 patients were included. Considering in-hospital mortality and creatinine value at admission, the best cut-off point to discriminate a death during hospitalization was 1.115 mg/dL. The logistic regression demonstrated that factors independently associated with mortality were age (OR 1.082, CI: 1.054-1.110), Charlson Comorbidity Index (CCI) (OR 1.341, CI: 1.178-1.526), and an abnormal creatinine value at admission, defined as equal to or above 1.12 mg/dL (OR 2.233, CI: 1.373-3.634). DISCUSSION: In conclusion, our study is in line with previous studies confirming that the creatinine serum level can predict mortality in COVID-19 patients and defining that the best cut-off of the creatinine serum level at admission to predict mortality was 1.12 mg/dL.

Pillars of long-term antiretroviral therapy success.

BACKGROUND: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. METHODS: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. RESULTS: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. CONCLUSIONS: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.

Real-life safety of Emtricitabine/Tenofovir Alafenamide/Bictegravir.

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 ART-naïve PLWH, blood lipids increased even though lipid profile did not worsen, and a trend towards normalization of liver enzymes was suggested. FTC/TAF/BIC is well tolerated in the real life setting.

Evaluation of Lipid Profile and Intima Media Thickness in Antiretroviral-Experienced HIV-Infected Patients Treated with Protease Inhibitor-Based Regimens versus Protease Inhibitor-Sparing Regimens.

BACKGROUND: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. The aim of our study was to evaluate whether patients treated with PIs have both greater dyslipidemia and increased intima media thickness (IMT) and atheromatous plaques compared to patients treated without PIs. MATERIALS AND METHODS: A total of 110 HIV-experienced patients screened with Doppler ultrasonography of the supra-aortic trunks in December 2019 were enrolled in a retrospective cross-sectional observational study. Patients were divided into two groups: 59 in the PI-based group, treated with PIs, and 51 in the PI-sparing group. In the two groups, we evaluated lipids, cardiovascular risk factors (smoking, BMI, age, hypertension), increased pathological IMT (a value > 1 mm), and possible atheromatous plaque. RESULTS: Serum LDL (p 0.04) and percentage of patients with hypercholesterolemia (p 0.03) were higher in the PI-based than in the PI-sparing group. Doppler data showed a trend in increase of IMT > 1 in the PI-based group, which appeared statistically significant for the section of the left common carotid artery (p 0.03). However, in multivariate logistic regression models, none of the evaluated variables were significantly associated with IMT > 1. CONCLUSIONS: Our real-life data show that patients treated with PIs have a trend of developing both greater dyslipidemia and increased pathological IMT and atheromatous plaques These findings may be useful to optimize antiretrovirals for patients with cardiovascular risk factors.

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting.

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.

Prevalence and Epidemiological and Clinical Features of Bacterial Infections in a Large Cohort of Patients Hospitalized for COVID-19 in Southern Italy: A Multicenter Study.

BACKGROUND: The aim of this study was to evaluate the prevalence of bacterial infections and antimicrobial prescriptions in a large cohort of COVID-19 patients and to identify the independent predictors of infection and antibiotic prescription. METHODS: All consecutive patients hospitalized for COVID-19 from March 2020 to May 2021 at 1 of the 17 centers participating in the study were included. All subjects showing a clinical presentation consistent with a bacterial infection with microbiological confirmation (documented infection), and/or a procalcitonin value >1 ng/mL (suspected infection) were considered as having a coinfection (if present at admission) or a superinfection (if acquired after at least 48 h of hospital stay). RESULTS: During the study period, of the 1993 patients, 42 (2.1%) presented with a microbiologically documented infection, including 17 coinfections and 25 superinfections, and 267 (13.2%) a suspected infection. A total of 478 subjects (24.5%) received an antibacterial treatment other than macrolides. No independent predictors of confirmed or suspected bacterial infection were identified. On the contrary, being hospitalized during the second wave of the pandemic (OR 1.35, 95% CI 1.18-1.97, p = 0.001), having a SOFA score ≥3 (OR 2.05, 95% CI 1.53-2.75, p < 0.001), a severe or critical disease (OR 1.66, 95% CI 1.24-2.23, p < 0.001), and a high white blood cell count (OR 1.03, 95% CI 1.004-1.06, p = 0.023) were all independently related to having received an antimicrobial prescription. CONCLUSIONS: Our study reported a high rate of antimicrobial prescriptions despite a limited number of documented or suspected bacterial infections among the large cohort of hospitalized COVID-19 patients.

GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Obesity as a Risk Factor of Severe Outcome of COVID-19: A Pair-Matched 1:2 Case-Control Study.

BACKGROUND AND AIM: The nature of the association between obesity and poor prognosis of COVID-19 without the evaluation of other co-pathologies associated has not yet been clearly evaluated. The aim of the present pair-matched case-control study was to investigate the outcome of patients with SARS-CoV-2 infection in obese and non-obese patients matched considering gender, age, number of comorbidities, and Charlson Comorbidity Index. METHODS: All the adults hospitalized for SARS-CoV-2 infection and with BMI ≥ 30 kg/m2 were included (Cases). For each Case, two patients with BMI < 30 kg/m2 pair matched for gender, age (±5 years), number of comorbidities (excluding obesity), and Charlson Comorbidity Index (±1) were enrolled (Controls). RESULTS: Of the 1282 patients with SARS-CoV-2 infection followed during the study period, 141 patients with obesity and 282 patients without were enrolled in the case and control groups, respectively. Considering matching variables, there was no statistical difference between the two groups. Patients in the Control group developed more frequently a mild-moderate disease (67% vs. 46.1%, respectively), whereas obese patients were more prone to need intensive care treatment (41.8% vs. 26.6%, respectively; p = 0.001). Moreover, the prevalence of death during hospitalization was higher in the Case group than in the Control group (12.1% vs. 6.4%, p = 0.046). DISCUSSION: We confirmed an association between obesity and severe outcome of patients with COVID-19, also considering other factors associated with a severe outcome of COVID-19. Thus, in the case of SARS-CoV-2 infection, the subjects with BMI ≥ 30 kg/m2 should be evaluated for early antiviral treatment to avoid the development of a severe course.

Outcome of patients with carbapenem-resistant Acinetobacter baumannii infections treated with cefiderocol: A multicenter observational study.

BACKGROUND: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections. METHODS: We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A. baumannii (CRAB) infections treated with cefiderocol, from June 12021 to October 30 2022. Primary endpoint was 30-day mortality, secondary end-points the clinical and microbiological response at 7 days and at the end of treatment. Furthermore, we compared the clinical and microbiological outcomes among patients who received cefiderocol in monotherapy or in combination. RESULTS: Thirty-eight patients with forty episodes of infection were included [mean age 65 years (SD+16.3), 75% males, 90% with hospital-acquired infections and 70% showing sepsis or septic shock]. The most common infections included unknown source or catheter-related bacteremia (45%) and pneumonia (40%). We observed at 7 days and at the end of therapy a rate of microbiological failure of 20% and 10%, respectively, and of clinical failure of 47.5% and 32.5%, respectively; the 30-day mortality rate was 47.5%. At multivariate analysis clinical failure at 7 days of treatment was the only independent predictor of 30-day mortality. Comparing monotherapy (used in 72.5%) vs. combination therapy (used in 27.5%), no differences were observed in mortality (51.7 vs 45.5%) and clinical (41.4 vs 63.7%) or microbiological failure (24.1 vs 9.1%). CONCLUSIONS: The findings of this study reinforce the effectiveness of cefiderocol in CRAB infections, also as monotherapy. However, prospective multicenter studies with larger sample sizes and a control group treated with standard of care are needed to identify the best treatment for CRAB infections.

Lipids and transaminase elevations in ARV-experienced PLWH switching to a doravirine-based regimen from rilpivirine or other regimens.

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, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF.

Analytical performance evaluation of Lumipulse® SARS-CoV-2 antigen assay in 392 asymptomatic patients.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is one of the current public health care challenges. The main strategy adopted to prevent the spread of infection is the rapid identification of COVID-19-positive subjects. The aim of this study was to compare the performance of Lumipulse® antigen immunoassay with the real-time RT-PCR, the gold standard for the diagnosis of SARS-CoV-2 infection, in a strictly selected asymptomatic population. MATERIALS AND METHODS: A total of 392 consecutive oro-nasopharyngeal swabs were collected from patients with no symptoms related to COVID-19 at the Emergency Department of AORN Sant'Anna e San Sebastiano, Caserta, Italy to evaluate the analytical performance of Lumipulse® SARS-CoV-2 antigen compared to qualitative real-time RT-PCR in asymptomatic patients. RESULTS: Lumipulse® SARS-CoV-2 antigen assay shows an overall agreement rate of 97% with a sensitivity of 96% and a specificity of 98%, with a PPV and NPV of 97%. The sensitivity varies according to the cycle threshold (Ct )-value reaching 100% and 86% with 15 < Ct < 25 and Ct ≥ 25, respectively. The ROC analysis yielded an AUC value of 0.98, suggesting that the antigen test may accurately detect SARS-CoV-2. CONCLUSION: Our data showed that Lumipulse® SARS-CoV-2 antigen assay might be an efficient tool in the identification and limitation of SARS-CoV-2 transmission in large asymptomatic populations.

Incident diabetes in course of antiretroviral therapy.

OBJECTIVE: Recent reports of excessive weight gain in people with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitors (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset. DESIGN: Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort. METHODS: All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM. RESULTS: 4366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4 + 460 [interquartile range (IQR) 256-710] cells/mm 3 cells/mm 3 . During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05-1.50).Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 kg 1.03; 95% CI 1.01-1.04), as well as older age (aHR 1.03 by 1 year; 95% CI 1.01-1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95% CI 1.48-3.49), having untreated high blood pressure (aHR 2.90; 95% CI 1.30-6.45) and baseline blood glucose >100 mg/dl (aHR 5.47; 95% CI 3.82-7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM. CONCLUSIONS: Baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort.

Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model.

OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens. DESIGN: In-vitro model of adipogenesis. METHODS: We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARÉ£ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment. RESULTS: Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF. CONCLUSION: Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.