Publications by authors named "Giovanni Cenderello"

67 Publications

The multidimensional prognostic index (MPI) for the prognostic stratification of older inpatients with COVID-19: A multicenter prospective observational cohort study.

Arch Gerontol Geriatr 2021 Apr 5;95:104415. Epub 2021 Apr 5.

Department of Primary Care, District 3, ULSS 3, Venice, Italy,; Department of Internal Medicine and Geriatrics, University of Palermo, Italy. Electronic address:

Background: The topic of prognosis in COVID-19 research may be important in adopting appropriate clinical decisions. Multidimensional prognostic index (MPI) is a frailty assessment tool widely used for stratifying prognosis in older people, but data regarding inpatients, affected by COVID-19, are not available.

Objectives: To evaluate whether MPI can predict in-hospital mortality and the admission to intensive care unit (ICU) in older inpatients hospitalized for COVID-19 infection.

Methods: In this longitudinal, Italian, multi-center study, older patients with COVID-19 were included. MPI was calculated using eight different domains typical of comprehensive geriatric assessment and categorized in three groups (MPI 1 ≤ 0.33, MPI 2 0.34-0.66, MPI 3 > 0.66). A multivariable Cox's regression analysis was used reporting the results as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: 227 older patients hospitalized for SARS-CoV-2 infection were enrolled (mean age: 80.5 years, 59% females). Inpatients in the MPI 3 were subjected less frequently than those in the MPI 1 to non-invasive ventilation (NIV). In the multivariable analysis, people in MPI 3 experienced a higher risk of in hospital mortality (HR = 6.30, 95%CI: 1.44-27.61), compared to MPI 1. The accuracy of MPI in predicting in hospital mortality was good (Area Under the Curve (AUC) = 0.76, 95%CI: 0.68-0.83). People in MPI 3 experienced a significant longer length of stay (LOS) in hospital compared to other participants. No association between MPI and ICU admission was found.

Conclusions: Frailty- as assessed by high MPI score - was associated with a significant higher risk of in-hospital mortality, longer LOS, and lower use NIV, whilst the association with ICU admission was not significant. These findings suggest that prognostic stratification by using the MPI could be useful in clinical decision making in older inpatients affected by COVID-19.
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http://dx.doi.org/10.1016/j.archger.2021.104415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020604PMC
April 2021

HCMV-controlling NKG2C NK cells originate from novel circulating inflammatory precursors.

J Allergy Clin Immunol 2021 Jan 23. Epub 2021 Jan 23.

Clinica Malattie Infettive, Ospedale Policlinico San Martino Istituto di Ricovero e Cura a Carattere Scientifico, Genova, Italy; Department of Life Sciences, University of Genova, Genova, Italy. Electronic address:

Background: There is limited knowledge on the origin and development from CD34 precursors of the ample spectrum of human natural killer (NK) cells, particularly of specialized NK subsets.

Objective: This study sought to characterize the NK-cell progeny of CD34DNAM-1CXCR4 and of other precursors circulating in the peripheral blood of patients with chronic viral infections (eg, HIV, hepatitis C virus, cytomegalovirus reactivation).

Methods: Highly purified precursors were obtained by flow cytometric sorting and cultured in standard NK-cell differentiation media (ie, SCF, FLT3, IL-7, IL-15). Phenotypic and functional analyses on progenies were performed by multiparametric cytofluorimetric assays. Transcriptional signatures of NK-cell progenies were studied by microarray analysis. Inhibition of cytomegalovirus replication was studied by PCR.

Results: Unlike conventional CD34 precursors, LinCD34DNAM-1CXCR4 precursors from patients with chronic infection, rapidly differentiate into cytotoxic, IFN-γ-secreting CD94/NKG2CKIRCD57 NK-cell progenies. An additional novel subset of common lymphocyte precursors was identified among LinCD34CD56CD16 cells and characterized by expression of CXCR4 and lack of perforin and CD94. LinCD34CD56CD16PerfCD94CXCR4 precursors are also endowed with generation potential toward memory-like NKG2CNK cells. Maturing NK-cell progenies mediated strong human cytomegalovirus-inhibiting activity. Microarray analysis confirmed a transcriptional signature compatible with NK-cell progenies and with maturing adaptive NK cells.

Conclusions: During viral infections, precursors of adaptive NK cells are released and circulate in the peripheral blood.
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http://dx.doi.org/10.1016/j.jaci.2020.12.648DOI Listing
January 2021

Is positivity for hepatitis C virus antibody predictive of lower risk of death in COVID-19 patients with cirrhosis?

World J Clin Cases 2020 Nov;8(22):5831-5834

Department of Biostatistics, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo 71013, Italy.

Liver injury has been reported in coronavirus disease 2019 (COVID-19) cases but the impact of pre-existing liver damage and related etiology have not been completely elucidated. Our research interests include the potential reciprocal influence of COVID-19 and pre-existing liver damage related to hepatitis C virus (HCV) infection, in particular. To this end, we have evaluated three cohorts of patients admitted at three Italian hospitals during the coronavirus pandemic; these included 332 patients with COVID-19 and 1527 patients with HCV who were from established real-world antiviral treatment study cohorts (sofosbuvir/velpatasvir), with either liver disease (various severities; = 1319) or cirrhosis ( = 208). Among the COVID-19 patients, 10 had cirrhosis (3%), including 7 of metabolic origin and 3 of viral origin. Mortality among the COVID-19 patients was 27.1%, with 70% of those with cirrhosis of metabolic etiology having died. Cirrhosis, older age, low white blood cell count and lymphocyte count being identified as risk predictors of death [odds ratio (OR) = 13.7, 95% confidence interval (CI): 2.59-83.01, = 0.006; OR = 1.05, 95%CI: 1.03-1.08, = 0.0001; OR = 1.09, 95%CI: 1.36-1.16, = 0.001; OR = 0.61, 95%CI: 0.39-0.93, = 0.023, respectively]. In the two cohorts of HCV patients, COVID-19 diagnosis was made in 0.07% of those with liver disease and 1% of those with cirrhosis. Thus, the prevalence of HCV antibodies among COVID-19-infected patients was comparable to that currently reported for the general population in Italy. Amongst the COVID-19 patients, pre-existing metabolic cirrhosis appears to be associated with higher mortality, while HCV antibodies may be suggestive of "protection" against COVID-19.
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http://dx.doi.org/10.12998/wjcc.v8.i22.5831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716316PMC
November 2020

HTA and HIV: The Case of Dual NRTI Backbones in the Italian Setting.

Int J Environ Res Public Health 2020 12 3;17(23). Epub 2020 Dec 3.

Centre on Health Economics, Social and Health Care Management, LIUC Business School, LIUC-Università Cattaneo, 21053 Castellanza, Italy.

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 2017-2018 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' 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; -value: 0.016) and social costs (FTC/TDF: -0.23, FTC/TAF: 1.04, ABC/3TC: 0.23; -value < 0.001), improving patient quality of life (FTC/TDF: 0.31, FTC/TAF: 1.85, ABC/3TC: 0.38; -value < 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.
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http://dx.doi.org/10.3390/ijerph17239010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729444PMC
December 2020

The impact of PrEP: results from a multicenter Health Technology Assessment into the Italian setting.

J Prev Med Hyg 2020 Sep 6;61(3):E451-E463. Epub 2020 Oct 6.

MEng, Centre for Health Economics, Social and Health Care Management, LIUC-Università Cattaneo, Castellanza, Italy - School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Introduction: The use of oral tenofovir/emtricitabine (FTC/TDF) for pre-exposure prophylaxis (PrEP) among high-risk people without Human Immunodeficiency Virus (HIV), is emerging as an innovative strategy to decrease HIV epidemic. The study aims at evaluating the implications related to PrEP introduction, from a multidimensional point of view, as required by Health Technology Assessment (HTA) approach, with a particular attention on sustainability and social factors, influencing PrEP implementation.

Methods: An analysis was conducted involving 35 Italian Infectious Disease Departments. The introduction of PrEP (applied both as "add-on" and "substitute" prevention strategy) into the clinical practice was compared with a baseline scenario, consisting of condoms among men who have sex with men, and serodiscordant couples, and the use of Needle Syringe Programme among injection drugs users The above scenarios were analysed by means of a Health Technology Assessment (HTA) approach. The 9 EUnetHTA Core Model domains were assessed through comparative information, retrieved from literature evidence, and collection of qualitative and quantitative information, derived from real-world evidence, in particular from 35 Infectious Disease Departments and potential PrEP' users involved. A final multi-criteria decision analysis approach (MCDA) was implemented to simulate the appraisal phase and providing evidence-based information with regard to the preferable technology.

Results: Despite the improvement in patients' quality of life, PrEP would generate the development of other sexually transmitted and blood-borne diseases, with a consequent decrease of patients' safety in case of PrEP applied as a "substitute" prevention strategy. In addition, PrEP would generate an increase in staff workflow, with investment in medical supplies and training courses. PrEP would lead to significant economic investments both for the NHS (+40%), and for citizens (+2,377%) if used as an add-on strategy, assuming FTC/TDF patent cost. With the off-patent drug, the NHS would benefit from an advantage (37%), and a shrink of the patients' expenditure emerged (+682%). More economic resources are required if PrEP is applied as a substitute strategy, considering both the patent (NHS: 212%; citizens: 3,423%) and the off-patent drug (NHS: 73%; citizens: 1,077%). Conclusions. The most cost-containing strategy would be the use of PrEP, as an add-on strategy, with a consequent improvement in patients' safety, even if drug-related adverse events would be considered. The implementation of the off-patent drug would decrease the economic burden of the innovative prevention strategy. Hence, the organizational aspects related to its adoption would be deeply investigated, with the potential opportunity to create specific ambulatories devoted to PrEP users' especially for medium and big size hospitals.
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http://dx.doi.org/10.15167/2421-4248/jpmh2020.61.3.1352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595079PMC
September 2020

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

JAMA Intern Med 2021 01;181(1):24-31

Malattie Infettive e Tropicali, AO S. Croce e Carle, Cuneo, Italy.

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile.

Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia.

Design, Setting, And Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein.

Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy.

Main Outcome And Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first.

Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility.

Conclusions And Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease.

Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.
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http://dx.doi.org/10.1001/jamainternmed.2020.6615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577199PMC
January 2021

Factors associated with hospital admission for COVID-19 in HIV patients.

AIDS 2020 11;34(13):1983-1985

Infectious Diseases Unit ASST-Monza, San Gerardo Hospital-University of Milano-Bicocca, Monza.

: This study reports on hospital admission and outcomes of 69 HIV-infected individuals who were diagnosed with SARS-CoV-2 infection between February and May 2020, in a network of Italian centres. Patients' characteristics and median days between symptoms and diagnosis were similar by hospital admission, whereas admitted patients had lower nadir CD4 cells and current lymphocytes count. These values were also correlated to worse COVID-19 outcome. Antiretroviral drugs did not seem to be associated with disease severity.
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http://dx.doi.org/10.1097/QAD.0000000000002663DOI Listing
November 2020

Factors Associated With Weight Gain in People Treated With Dolutegravir.

Open Forum Infect Dis 2020 Jun 26;7(6):ofaa195. Epub 2020 May 26.

Infectious Diseases Clinic, Department of Health Sciences, University of Genoa, San Martino Hospital-IRCCS, Genoa, Italy.

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/mm (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.
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http://dx.doi.org/10.1093/ofid/ofaa195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295329PMC
June 2020

Noninvasive liver fibrosis assessment in chronic viral hepatitis C: agreement among 1D transient elastography, 2D shear wave elastography, and magnetic resonance elastography.

Abdom Radiol (NY) 2019 12;44(12):4011-4021

Unit of Radiology, Department of Diagnostic Imaging, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy.

Purpose: To assess the agreement of one-dimensional transient elastography (1D-TE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) in a consecutive cohort of patients affected by hepatitis C virus (HCV) and to understand which patient-related factors are associated with disagreement.

Methods: Ninety-one consecutive patients with current or previous chronic HCV infection were enrolled between March 2017 and September 2018. We assessed the correlation between stiffness measurements expressed in kilopascals (kPa). After converting kPa values in three groups of increasing fibrosis burden using validated cut-off values, we assessed the agreement among the different techniques. Factors influencing inter-modality disagreement were examined by employing multivariate logistic regression analysis.

Results: Seventy-seven patients met the inclusion criteria and had reliable measurements by all stiffness imaging techniques. At the quantitative analysis, a strong correlation between stiffness measurements was found (Spearman's rho values ranging from 0.7 to 0.89 in all pairs of techniques). Complete concordance among MRE, 1D-TE, and 2D-SWE was found in 64.9% of patients, and the agreement was highest between MRE and 1D-TE, with κ value of 0.801. In only 2/77 patients (2.6%), there was complete disagreement. High body mass index (BMI) was the only factor significantly associated with inter-modality discordance.

Conclusions: MRE, 1D-TE, and 2D-SWE assigned the majority of patients to the same fibrosis group. The agreement was at least good, and there was a strong correlation between kPa values in all three pairs of techniques. Highest agreement was found between MRE and 1D-TE. High BMI was associated with discordance among the techniques.
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http://dx.doi.org/10.1007/s00261-019-02295-7DOI Listing
December 2019

Response to letter to the editor: switch to dolutegravir and unboosted atazanavir.

AIDS 2019 11;33(14):2263-2264

aInfectious Diseases Unit, San Martino Policlinic Hospital bInfectious Diseases Unit, Department of Health's Sciences, University of Genoa cInfectious Diseases Unit, Galliera Hospital, Genoa dDepartment of Infectious Diseases, Sacco Hospital, Milan, Italy.

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http://dx.doi.org/10.1097/QAD.0000000000002330DOI Listing
November 2019

Delay in schistosomiasis diagnosis and treatment: a multicenter cohort study in Italy.

J Travel Med 2020 Feb;27(1)

Clinic of Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy.

Background: Barriers to access to care, different diagnostic strategies and low awareness remain challenging issues in the fight against schistosomiasis.Our study aims to examine management of schistosomiasis in migrants attending large tertiary hospitals in Italy, in order to call for a comprehensive approach.

Methods: A retrospective review of schistosomiasis cases was carried out between January 1, 2016, and December 31, 2017, in five large Infectious Disease Centers in Italy. We included all patients diagnosed with schistosomiasis. We differentiated among (i) asymptomatic patients diagnosed by serology either as healthy 'migrant evaluation' or as 'late evaluation' in patients followed because of a different infection and (ii) patients tested because of a suggestive clinical presentation. Patients characteristics and clinical data were recorded.

Results: One hundred forty-nine patients were included, 137 (91.9%) were male, the median age was 26 years and 70% of them came from Sub-Saharan Africa.Thirty-eight asymptomatic patients (25.5%) were diagnosed by serology [15, (10.1%) among 'migrant evaluation' and 23 (15.4%) among 'late evaluation' group], and 111 (74.5%) presented with signs/symptoms.The median diagnostic delay from arrival in Italy was 31 months: 110 for asymptomatic group and 16 months for symptomatic patients. Among the 111 symptomatic patients, 41 individuals were already followed in our clinics, and they never underwent screening before appearance of evident disease. Among patients with positive serology who were tested by microscopy, 32/86 (37.2%) had confirmed diagnosis. Forty-five (37.8%) patients presented radiologic abnormalities. Praziquantel was the treatment of choice (70.1% for 3 days and 29.9% in a single-day dose), and 77 (51.7%) were lost to follow-up.

Conclusions: In our centers, a high proportion of patients were tested late after arrival, and most of them presented with clinical apparent disease. Well-defined strategies and implementation of recent guidelines are needed to improve early diagnosis and to overcome heterogeneity of practice.
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http://dx.doi.org/10.1093/jtm/taz075DOI Listing
February 2020

The Ligurian HIV Network: How Medical Informatics Standards Can Help Clinical Research.

Stud Health Technol Inform 2019 Aug;264:1666-1667

Department of Informatics, Bioengineering, Robotics and System Engineering, (DIBRIS), University of Genoa, Italy.

Integrating evidence from systematic research in daily clinical practice is one of the pillars of evidence-based medicine. Electronic data capture tools simplify data collection from different centers and supports the management of multicenter clinical trials. The Ligurian HIV Network (LHN) is one such tool, originating from a regional effort to integrate clinical trial capabilities for HIV and other chronic infectious diseases. In order to manually collect a complete report of all clinical tests on patients enrolled in a trial, a strenuous human effort and the allocation of great resources would be necessary. Moreover, the risk of error in a manual system is very high. The proposed system automatically extracts clinical data from the EHR of three hospitals of the LHN in a standardized way, and enhance their re-use in clinical trials. Through dedicated questionnaires, physicians reported a strongly positive feedback about the efficacy of the platform in supporting clinical research.
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http://dx.doi.org/10.3233/SHTI190587DOI Listing
August 2019

A Web-Based Tool for a Complete Evaluation of Fragility in Senior Hiv+ Patients.

Stud Health Technol Inform 2019 ;261:299-302

Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genoa, Italy.

Background: after the discovery of the antiretroviral therapy, life expectancy of HIV+ patient has become longer and this meant that he would start ageing. International literature demonstrated that the HIV+ patient is more fragile than any other person of the same age and that doesn't present the viral infection.

Objective: design, development and test of a new web-based instrument to allow the self-administration of the new questionnaire SELFY MPI created during the European project Effichronic. Materials & Methods: between June and September 2018, a group of senior 50 HIV+ patients, was involved. The questionnaire SELFY MPI enables to collect data about quality of life and cognitive functions.

Results: the developed web-instrument collects pseudo-anonymous data into the Liguria HIV Network database. The subsequent statistical analysis highlighted a correlation between the two outcomes of SELFY MPI and the laboratory exam's parameter TCD4+ and viral load.

Conclusions: the great potentiality of this instrument is not only the support given to clinical research about the effects of HIV on chronical disease management but it can be also used as a follow-up instrument to evaluate different aspects of the geriatric patient life during the years.
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September 2019

SVR12 Higher than 97% in GT3 Cirrhotic Patients with Evidence of Portal Hypertension Treated with SOF/VEL without Ribavirin: A Nation-Wide Cohort Study.

Cells 2019 04 4;8(4). Epub 2019 Apr 4.

Gastroenterology Unit, Università di Torino, 10124Torino, Italy.

In clinical trials, a sofosbuvir/velpatasvir (SOF/VEL) pangenotypic single-tablet regimen was associated with high sustained virological response (SVR) rates at 12 weeks (SVR12) after the end of treatment, regardless of genotype and fibrosis stage. No real-life data on genotype 3 (GT3) cirrhotic patients with portal hypertension are available. The aim of this study was to assess the effectiveness of SOF/VEL in GT3 cirrhotics with portal hypertension. Patients with GT3 and advanced cirrhosis were treated for 12 weeks with SOF/VEL without ribavirin at five different centers in Italy from June 2017 to August 2018 and their SVR12 was assessed. Of the 227 GT3 cirrhotics evaluated, 205 met the inclusion criteria and 111 had transient elastography results ≥20 KPa. SVR12 was 97.6% (95% CI 94.4-98.9), rates were 99.1% (95% CI 95.7-99.8) in patients with ≥20 KPa and 95.8% (95% CI 89.5-98.3) in those with <20 KPa (p = 0.18). Analyzed by presence of esophageal varices, the SVR12 rates were 98.4% (95% CI 91.4-99.7) and 97.1% (95% CI 92.9-98.9) in patients without and with varices, respectively (p = 1.0). In real life, SOF/VEL GT3 cirrhotic patients with evidence of portal hypertension can achieve SVR12 levels comparable to those of patients without portal hypertension. These SVR12 rates are similar to what is reported in compensated cirrhosis treated within clinical trials.
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http://dx.doi.org/10.3390/cells8040313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523403PMC
April 2019

Durability of dolutegravir plus boosted darunavir as salvage or simplification of salvage regimens in HIV-1 infected, highly treatment-experienced subjects.

HIV Clin Trials 2018 12;19(6):242-248

a 1st Division of Infectious Diseases , ASST Fatebenefratelli-Sacco , Milano , Italy.

Background: Dolutegravir (DTG) plus boosted darunavir (bDRV) is a compact, adherence-friendly salvage regimen with the highest genetic barrier to HIV-1 resistance.

Objective: Aim of the present study is to assess the long term (96-week) safety and efficacy of DTG + bDRV in a of multidrug-experienced HIV-1 infected patients, simplifying or building rescue regimens.

Methods: All HIV-1-infected subjects from eleven Italian centers switched to DTG + bDRV between March 2014 and September 2015 were included and followed for minimum 96 weeks.

Results: The cohort comprises 130 subjects, switched from 42 different, complex or at least twice-daily regimens, mainly for simplification (44.6%), viral failure (30.0%) or toxicity (16.6%). At baseline 118 had documented resistance to 1-5 antiretroviral classes and 12 lacked genotypic results either for historical reasons or for problems with primer annealing; 52 (40%) had uncontrolled viral replication, three above 500.000 copies/mL. At week 96 two showed ≥50 HIV-1 RNA copies/mL, 23 had 1-49 copies/mL and 101 had no virus detected. The proportion of subjects presenting abnormal values at baseline significantly decreased for serum glucose, creatinine, AST, total cholesterol and triglycerides.

Conclusions: These long-term data confirm the reliability of the two-drug regimen consisting of bDRV plus DTG in salvage settings in HIV-1 infection.
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http://dx.doi.org/10.1080/15284336.2018.1550290DOI Listing
December 2018

Prevalence and predictors of malignancies in HIV patients: results of a retrospective multicentric Italian cohort.

Infez Med 2019 Mar;27(1):53-57

Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy.

We report the sharp reduction in the incidence of AIDS defining cancers in a multicentric, retrospective study carried out since 1991 and involving six Infectious Diseases Units spread across Italy. However, due to the parallel increase in non-AIDS defining cancers, cancer incidence was not reduced. Focusing on predictors of death in HIV-positive patients with neoplastic disease, multivariate models revealed that males as well as drug abusers were independently associated with a poor clinical outcome.
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March 2019

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry.

J Chemother 2019 Feb 3;31(1):9-14. Epub 2018 Dec 3.

q Infectious Diseases Unit , Legnago Hospital , Verona , Italy.

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016-September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.
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http://dx.doi.org/10.1080/1120009X.2018.1536320DOI Listing
February 2019

Treatment of hepatitis C virus genotype 4 in the DAA era.

Virol J 2018 11 22;15(1):180. Epub 2018 Nov 22.

Infectious Disease Unit, EO Ospedali Galliera, via Mura delle Cappuccine n 14, 16128, Genoa, Italy.

The recently approved interferon-free DAA (direct antiviral agents) regimens have shown not only to be effective in terms of sustained virological response (SVR) rates (> 90%) but also well tolerated in most hepatitis C virus (HCV) infected patients. Nevertheless HCV genotypes are different and only a small percentage of trials consider genotype 4 (GT4), which was associated with lower rates of SVR compared with other genotypes before the arrival of the DAA's. In this review, we discuss the efficacy of DAA therapy in GT4 HCV infection with specific reference to more recent studies, including those conducted in a 'field-practice' scenario. Overall, DAA-based regimens appear more effective also in the poorly-explored setting of patients with HCV GT4 infection. Despite an overall limited number of patients was evaluated, favorable results are being derived from studies on ombitasvir/paritaprevir/ritonavir, sofosbuvir and velpatasvir, whether or not in association with voxilaprevir, and with the new combined therapy glecaprevir + pibentasvir.
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http://dx.doi.org/10.1186/s12985-018-1094-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251143PMC
November 2018

HCV elimination plan leads to significant benefits in managing liver-related diseases and hospital interventions: a regional simulation.

Expert Rev Pharmacoecon Outcomes Res 2019 Apr 22;19(2):189-193. Epub 2018 Oct 22.

g Infectious Diseases Unit , Hospital Policlinico San Martino , Genoa , Italy.

Objectives: This article presents a 3-year budget impact simulation on the effects of a chronic Hepatitis C (HCV) eradication plan in real-life costs incurred by the Regional Health Service.

Methods: The Liguria Region network performed a prospective 3-year (2017-2019) timeframe horizon trends simulation analysis focusing on management interventions and costs. It involved all the eight prescribing centers in the region, starting from retrospective historical performance data and assuming the impact of sustained viral response rates for patients treated for HCV. Data on hospital admissions, medical visits, number of patients, and deaths were collected through the healthcare database.

Results: At the beginning of 2017, 2,940 patients were eligible for HCV treatment with direct-acting antivirals. Assuming to treat this entire population with a success rate of 90%, the events related to liver complications in the horizon would decrease to 5,538 cumulatively (-35%), with a 27% reduction of direct costs, showing a global savings of 24,779.024 Euros.

Conclusion: Treating the entire eligible HCV population would lead to significant benefits and savings in managing liver-related diseases and their direct costs, opening opportunities to re-think new settings for the future organization of liver disease management in the regional health system.
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http://dx.doi.org/10.1080/14737167.2019.1537124DOI Listing
April 2019

A case report of mucocutaneous tuberculosis after orthotopic liver transplantation: a challenging diagnosis.

BMC Infect Dis 2018 Aug 29;18(1):431. Epub 2018 Aug 29.

TB Supranational Reference Laboratory, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Mycobacterium tuberculosis is responsible for high morbidity and mortality in immune-compromised hosts.

Case Presentation: We present a rare case of cutaneous tuberculosis after orthotopic liver transplantation without involvement of any other organs.

Conclusion: TB risk-factors assessment, careful LTBI screening and treatment according to national guidelines, as well as a reduction in missed opportunity for prevention are necessary to avoid MTB related disease in fragile patients.
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http://dx.doi.org/10.1186/s12879-018-3347-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114782PMC
August 2018

Real life rates of sustained virological response (SVR) and predictors of relapse following DAA treatment in genotype 3 (GT3) patients with advanced fibrosis/cirrhosis.

PLoS One 2018 31;13(7):e0200568. Epub 2018 Jul 31.

Liver Unit, "Casa Sollievo della Sofferenza", IRCCS, San Giovanni Rotondo, Italy.

Background: Treatment of GT3 remains challenging compared to other genotypes.

Aims: To explore real life SVR rates and to identify predictors of virological failure across the most recently used Direct acting antiviral (DAA) regimens in a large cohort of Italian patients with cirrhosis or advanced fibrosis (F3 or F4).

Methods: Between May 2015 and June 2017, the combinations of sofosbuvir (SOF) plus daclatasvir (DCV) ± RBV and SOF plus velpatasvir (VEL) ± RBV become available in our Country. Patients were treated following Italian guidelines within a protocol implemented by 11 centers working together on genetics.

Results: Of 336 patients, 38.1% were Peg/IFN-experienced. SOF/DCV was used in 65.1%, SOF/VEL in the remaining. Overall SVR12 was 90.2% ranging from 87.2% after SOF/DCV to 95.7% after SOF/VEL (p = 0.012). No additional benefits of RBV use were observed for both regimens. 155 patients (46.1%) had cirrhosis. SVR12 was 87.1% (135/155) for cirrhotic patients and 92.8% (169/182) for non-cirrhotic (p = 0.09). NS5A-RASs were present at baseline in 6.4% of patients, PNPLA3GG and IL28BCC genotypes in 7.3% and 33.0%, respectively. No association between favorable genetics and SVR12 was observed. Predictors of relapse were: history of Peg/IFN/RBV failure (OR = 6.34, 95% CI 2.04-19.66, P = .001), baseline NS5A-RASs (OR = 8.7, 95% CI 1.58-47.92, P = 0.013) and treatment regimen (OR = 5.57 95% CI 1.64-18.95.96, P = 0.006).

Conclusions: Our real-world results validate the efficacy of current GT3 IFN-free regimens suggesting that, among patients with severe disease, Peg/IFN/RBV experience and NS5A associated RASs are predictors of relapse. Their relevance can be expected to decline with the use of SOF/VEL. (250).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0200568PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067691PMC
January 2019

Hypertensive Versus HIV-infected Patients: Who Has the Greatest Target Organ Damage? Comparison of Carotid Plaque Prevalence, Intima Media Thickness and Renal Resistive Index in the Two Groups of Patients.

Curr Hypertens Rev 2018 ;14(1):48-55

Infectious Diseases Unit, Hospital Policlinico San Martino, University of Genoa, Genoa, Italy.

Objectives: to compare the prevalence of target-organ damage (TOD), defined as carotid plaque, or intima media thickness, cIMT, >0.9 mm, and that of increased renal resistive index (RRI), among HIV-1-infected patients and uninfected hypertensive patients (HT-non HIV).

Methods: HIV-infected patients aged ≥ 18 years and virologically suppressed were matched with pair-age, sex and BMI HT-non HIV. Patients on antihypertensive treatment were excluded. All patients' cIMT and RRI were evaluated with ultrasonography. Data were analysed throughout Χ2 test, analysis of variance and logistic regression.

Results: Fifty-nine HIV-infected patients were enrolled (71% men) and matched with 59 HT-non HIV. No differences were found in cIMT values (p=0.827) and in the prevalence of TOD between HIV-infected patients and HT-non HIV (36% vs 38%, p= 0.79). Among HIV-infected patients, those hypertensive had significantly higher prevalence of TOD (46% vs 21%, P< 0.05) and higher cIMT (0.747 ± 0.104 vs 0.654 ±0.100 mm, p = 0.0185). Patients with TOD were older (p= 0.004) and more frequently current smokers (p= 0.022). At the logistic regression analysis, TOD was significantly related to age (p=0.04, 95%CI 1.0-1.1) and smoke, current (p=0.178, 95%CI1.2-12.8) or previous (p=0.04, 95%CI 1.0-7.2). Mean RRI were identical for both HIV-1 infected and uninfected patients (0.60, SD± 0.05 and 0.60, SD± 0.04, respectively, p=0.996).

Conclusions: In our study TOD was associated to hypertension, older age and smoke, but not to HIV serostatus itself, confirming the major importance of traditional risk factors and the need of risk assessment and cardiovascular prevention measures in HIV-infected patients.
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http://dx.doi.org/10.2174/1573402114666180307145051DOI Listing
April 2019

From Liguria HIV Web to Liguria Infectious Diseases Network: How a Digital Platform Improved Doctors' Work and Patients' Care.

AIDS Res Hum Retroviruses 2018 03 21;34(3):239-240. Epub 2018 Feb 21.

1 Department of Informatics, Bioengineering, Robotics and System Engineering, (DIBRIS), University of Genoa , Genoa, Italy .

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http://dx.doi.org/10.1089/aid.2017.0064DOI Listing
March 2018

CD8CD28CD127CD39 regulatory T-cell expansion: A new possible pathogenic mechanism for HIV infection?

J Allergy Clin Immunol 2018 06 2;141(6):2220-2233.e4. Epub 2017 Nov 2.

Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Azienda Ospedaliero Universitaria San Martino, IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. Electronic address:

Background: HIV-associated immunodeficiency is related to loss of CD4 T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4 T cells/μL. CD8CD28CD127CD39 T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients.

Objectives: We sought to analyze the frequency of CD8CD28CD127CD39 Treg cells in the circulation of HIV-infected patients.

Methods: The frequency of circulating CD8CD28CD127CD39 Treg cells was analyzed and correlated with viral load and CD4 T-cell counts/percentages in 93 HIV-1-infected patients subdivided as follows: naive (n = 63), elite controllers (n = 19), long-term nonprogressors (n = 7), and HIV-infected patients affected by tumor (n = 4). The same analyses were performed in HIV-negative patients with cancer (n = 53), hepatitis C virus-infected patients (n = 17), and healthy donors (n = 173).

Results: HIV-infected patients had increased circulating levels of functional CD8CD28CD127CD39 Treg cells. These cells showed antigen specificity against HIV proteins. Their frequency after antiretroviral therapy (ART) correlated with HIV viremia, CD4 T-cell counts, and immune activation markers, suggesting their pathogenic involvement in AIDS- or non-AIDS-related complications. Their increase after initiation of ART heralded a lack of virologic or clinical response, and hence their monitoring is clinically relevant.

Conclusion: HIV infection induces remarkable expansion of CD8CD28CD127CD39 Treg cells, the frequency of which correlates with both clinical disease and signs of chronic immune cell activation. Monitoring their frequency in the circulation is a new marker of response to ART when effects on viremia and clinical response are not met.
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http://dx.doi.org/10.1016/j.jaci.2017.08.021DOI Listing
June 2018

Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus.

J Antimicrob Chemother 2018 Jan;73(1):177-182

Clinic of Infectious Diseases, Istituto Scientifico San Raffaele, Milano, Italy.

Objectives: This study evaluated the virological efficacy of dolutegravir 50 mg twice daily in 190 HIV-1 failing antiretroviral-experienced patients with previous exposure to first-generation integrase strand transfer inhibitor (INSTI) over a 5 year follow-up using data from clinical practice.

Patients And Methods: This analysis included HIV-1-infected patients who were ≥18 years of age, treatment experienced, had HIV-1 RNA >50 copies/mL, with INSTI-resistant virus, who started dolutegravir 50 mg twice daily plus optimized background therapy (OBT), recorded in the national prospective database PRESTIGIO (www.progettoprestigio.it). Follow-up accrued from the start of dolutegravir 50 mg twice daily + OBT until virological failure (VF) or dolutegravir discontinuation for any reason or the last treatment visit on dolutegravir 50 mg twice daily treatment. VF was defined by the lack of achievement of HIV-1 RNA <50 copies/mL by 6 months and thereafter, or the occurrence of two consecutive HIV-1 RNA ≥50 copies/mL after achievement of undetectable viral load.

Results: The estimated VF probabilities were 17% (95% CI = 12%-24%), 28% (95% CI = 21%-37%), 33% (95% CI = 25%-43%), 39% (95% CI = 29%-51%) and 52% (95% CI = 39%-67%) at 12, 24, 36, 48 and 60 months since baseline, respectively. A higher risk of VF was independently associated with baseline viral load >100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with ≥1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015).

Conclusions: Our data showed a favourable long-term efficacy of dolutegravir 50 mg twice daily in association with OBT in treatment-experienced failing subjects, with INSTI-resistant virus, in the real world. A close monitoring of adherence is crucial for maintenance of virological response in this fragile subgroup of subjects.
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http://dx.doi.org/10.1093/jac/dkx371DOI Listing
January 2018

Role of Raltegravir in patients co-infected with HIV and HCV in the era of direct antiviral agents.

New Microbiol 2017 Oct 10;40(4):227-233. Epub 2017 Oct 10.

Clinic of Infectious Diseases, Policlinico Ospedale San Martino, Genova, Italy.

Integrase strand transfer inhibitors (INSTIs) are the preferred third agent in first-line antiretroviral therapies. Raltegravir (RAL) was the first INSTI to be approved and used in naïve and experienced patients. Due to its good tolerability and low side effects, RAL has been largely used also in hepatitis coinfected patients. Many years of experience in RAL use now allow literature evidence to be gathered on its safety in HIV/HCV-co-infected patients pre, during and post direct acting agents (DAA) treatment, at all possible stages. In both clinical trials and published case series, RAL has been well tolerated in patients harboring HCV co-infection and also in cirrhotic patients with mild hepatic impairment. Literature data show no major interactions or the need for dose adjustments with any of the DAA currently in use for HCV treatment, or with ribavirine. Hence, RAL can be safely administered during HCV treatment with DAA and may be used as a "temporary" regimen in patients who do not present major integrase-inhibitor mutations. Moreover, its characteristics are also favorable in case of orthotropic liver transplantation, both for the evidence of hepatic safety and for possible co-administration with immunosuppressant agents.
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October 2017

A dual regimen of ritonavir/darunavir plus dolutegravir for rescue or simplification of rescue therapy: 48 weeks' observational data.

BMC Infect Dis 2017 09 30;17(1):658. Epub 2017 Sep 30.

1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Via Giovanni Battista Grassi, 74, pavillion 56, Malattie Infettive, 2nd floor, 20157, Milan, Italy.

Background: Dolutegravir (DTG) plus darunavir/ritonavir (DRV/r) is a simple combination of drugs that has the best genetic barrier to HIV-1 resistance and may be fit for salvage therapy.

Methods: All HIV-1-infected subjects treated with DTG plus DRV/r between March 2014 and September 2015 in eight Italian centres were included in the analysis. The main metabolic data, efficacy parameters and safety data routinely collected were provided. This observational study is aimed to assess the efficacy of such approach. The primary end-point was the proportion of subjects achieving or maintaining virologic suppression <50 copies/mL at week 24. Secondary end points were maintaining virologic suppression in the follow-up (weeks 48 and 96) and safety.

Results: One hundred and thirty subjects were followed for a median of 56 months. Reasons for switching were simplification (44.6%), viral failure (30%), toxicity (16.9%), non-adherence (4.6%), persistent low-level viremia (3.1%), and drug-drug interaction (0.8%). At baseline, 118 subjects had documented resistance to 1 to 5 antiretroviral classes while 12 had viral rebound at a time when genotypic tests were not yet available. Seventeen and 14 subjects took DRV/r and DTG twice daily, respectively. One subject was lost to follow-up, one discontinued for liver enzymes' elevation, one died of illicit drug abuse and one of cancer-related complications. The proportion of subjects with ongoing HIV replication dropped from 40% to 6.1%. Those with undetectable viral load increased from 38.5% to 76.2%. At week 48, 17.7% had HIV RNA between 1 and 49 copies/mL. The number of subjects with altered serum glucose, creatinine, ALT, AST, total-, HDL- and LDL-cholesterol, triglycerides and MDRD <90 mL/min decreased by week 48, while those having MDRD <60 mL/min remained 4.6%. Overall 90/283 baseline laboratory alterations returned to normality.

Conclusions: Switching to DTG plus DRV/r proved to be safe, suppressing viral replication without metabolic impact.
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http://dx.doi.org/10.1186/s12879-017-2755-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622573PMC
September 2017