Search

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

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

Antiretroviral therapies have been tested with the goal of maintaining virological suppression with a particular attention in limiting drug-related toxicity. With this aim we designed the DUAL study: a randomized, open-label, multicenter, 96 weeks-long pilot exploratory study in virologically suppressed HIV-1+ patients with the aim of evaluating the immunovirological success and the impact on non-HIV related morbidity of switching to a dual therapy with darunavir-ritonavir (DRV/r) and rilpivirine (RPV). We recruited patients who received a PI/r-containing HAART for >=6 months, HIV-RNA < 50 cp/mL for >=3 months, eGFR > 60 mL/min/1,73m2, without DRV or RPV RAMs. We randomized patients in arm A: RPV + DRV/r QD or arm B: ongoing triple therapy. The primary endpoint has been defined as the percentage of patients with HIV-RNA < 50 cp/mL at week 48 (ITT). VACS index, Framingham CVD risk (FRS) and urinary RBP (uRBP) were calculated. We used Chi-square or Fisher statistics for categorical variables and Mann-Whitney U for continuous ones. Forty-one patients were enrolled (22 in arm A, 14 in arm B, plus 5 screening failures): 30 patients reached 96 weeks: 100% had HIV-RNA < 50 cp/mL in arm A versus 91.7% in arm B. Similar changes were observed in median CD4/mL between baseline and week 96 (+59 versus - 31, p: n.s.). Thirty-one in arm A and 23 in arm B adverse events took place, whereas only 1 was serious (arm A: turbinate hypertrophy, unrelated to HAART). Among the 6 discontinuations (3 in A, 3 in B), only 1 was related to adverse event (arm A: G3 depression, insomnia, weakness). VACS index, median FRS and median uRBP values did not vary from baseline to week 96. At 96-weeks all patients switched to a QD 2-drug regimen based on DRV/r + RPV maintained HIV-RNA suppression, but a single patient who showed a virological failure at week 4. CD4 counts increased overtime without significant differences between the two arms. The novel dual regimen was well tolerated with the same amount of discontinuation as the control arm. VACS index, FRS and uRBP did not differ between arms at week 96.

One of the most important Staphylococcus aureus virulence factors is Panton–Valentine leukocidin (PVL). We describe an outbreak of recurrent cutaneous PVL infections in different members of three family clusters. Molecular investigations were performed to confirm the presence of the mecA and PVL genes and to assign the SCCmec type, sequence type (ST) and clonal relatedness. A strain of PVL-producing methicillin-resistant S. aureus (MRSA) was responsible for infection in two related families (A and B), and a third family (C) was infected with PVL-producing methicillin-sensitive S. aureus (MSSA). Molecular investigations revealed the same clone of community-acquired (CA)-MRSA, PVL positive ST8, and SCCmec IV in families A and B and CA-MSSA PVL positive ST15 in family C. S. aureus PVL may give rise to recurrent uncontrolled infections that are difficult to eradicate, and close family contacts are at high risk for transmission. Keywords: Panton–Valentine leukocidin, Community-acquired methicillin-resistant Staphylococcus aureus

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

Background Gastrointestinal basidiobolomycosis (GIB) is a rare mycosis affecting almost exclusively immunocompetent subjects. Methods We describe a case of GIB caused by Basidiobolus ranarum in a 25-year-old Italian immunocompetent man resident in Ireland who presented a 2-month history of epigastric pain. Suspecting colon cancer he underwent a right hemicolectomy subsequently leading to a diagnosis of GIB by means of molecular biology. After surgery a 9-month therapy with itraconazole was employed with a good outcome. A review of medical literature regarding GIB cases published in the period 1964–2017 is presented. Results One-hundred and two cases of GIB were included in this analysis. The disease was observed predominantly in male gender (74.5%) and children (41.2%). Abdominal pain was the single most common complaint (86.3%) followed by fever (40.2%) and evidence of an abdominal mass (30.4%). Peripheral blood eosinophilia was detected in 85.7% of cases. Most of the patients were diagnosed in Saudi Arabia (37.2%) followed by USA (21.6%) and Iran (20.6%). Surgery plus antifungal therapy was employed in the majority of patients (77.5%). An unfavourable outcome was documented globally in 18.6% of patients. Conclusions GIB seems to be an emerging intestinal mycosis among immunocompetent patients living in the Middle East and Arizona.

We evaluated predictive factors involved in durability and therapeutic failure of atazanavir (ATV)-based antiretroviral regimens with or without ritonavir (r) in real life setting. This retrospective study of HIV-1-positive patients evaluated the factors related to ATV continuance and the time-dependent probability of therapeutic failure (HIV-RNA >200 copies/mL and concomitant discontinuation of ATV). We also investigated the rate of therapeutic failure and the variations in total bilirubin levels from starting unboosted ATV-based regimens. The study involved 1030 patients: 183 treatment-naive patients (17.8%) started ATV/r (17 subsequently switched to unboosted ATV); 653 (63.4%) switched to ATV/r from previous antiretroviral regimens (121 subsequently switched to unboosted ATV); and 194 (18.8%) switched to unboosted ATV from previous ATV-free regimens. The median ATV follow-up was 28 months (interquartile range 7-56). The risk of ATV discontinuation was significantly lower in patients switched to unboosted ATV from ATV/r (HR 0.45; p < 0.0001). The discontinuation of ATV correlated with female gender (HR 1.26; p = 0.035), use of a zidovudine/didanosine/stavudine containing backbone (HR 1.8; p = 0.004), and a baseline CD4+ cell counts of

1 Infectious Diseases Unit, Department of Biomedical and Clinical Sciences “Luigi Sacco”, Universita degli Studi di Milano, Milan, Italy. 2 Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy. 3 Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences “Luigi Sacco”, Universita degli Studi di Milano, Milan, Italy. 4 University Division of Infectious Diseases, University of Siena, Siena, Italy. 5 Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy. 6 Unit of Clinical Pharmacology, CNR Institute of Neuroscience, Department of Biomedical and Clinical Sciences “Luigi Sacco”, Universita degli Studi di Milano, 20157 Milan, Italy.

Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine. Keywords: HIV, Abacavir, Liver toxicity

Introduction Since antiretroviral therapy must be taken lifelong, persistence and safety have become the goals to achieve. Protease inhibitors, in particular atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed class in real life long-term treatment. Methods We conducted a retrospective cohort study in HIV-1-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load, CD4 lymphocytes and the mean blood chemistry parameters were collected at baseline, first, third, sixth months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and time-dependent probability to reach a CD4 cells count >500 cells/µL were evaluated with Kaplan-Meier curve and Cox model. Results A total of 1030 patients were evaluated: 183 received therapy with ATV/r as naïve, 653 switched to ATV/r as a second or following line and 194 switched to unboosted ATV from previous ATV-free regimens. A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen (17 from naïve ATV/r and 121 from experienced ATV/r). The median duration of therapy was 38 months (95% CI 29–73) in ATV/r naïve patients, 36 months (95% CI 23–53) in unboosted ATV group and 35 months (95% CI 31–43) in patients switched to ATV/r. We observed no significant difference in the persistence of the three regimens (p=0.149). Female (HR=1.317; 95% CI 1.073–1.616 p=0.008) and patients with CD4500 cells/µL. Factors associated to a poor CD4 gain were each extra Log of viral load at baseline (HR=0.915; 95% CI 0.852–0.982 p=0.014) and CD4

Graphene is a recently discovered material consisting of a two-dimensional sheet of Carbon atoms arranged in an hexagonal pattern. It is a zero-gap semimetal whose electrical properties can be tuned by controlled induction of defects such as vacancies. In this work, graphene flakes were produced with the standard method of mechanical exfoliation. Afterward, we have used light optical microscopy (LOM), atomic force microscopy (AFM), Raman spectroscopy and in-situ electrical measurements to investigate the changes in structural and electrical properties after defect introduction by ion irradiation. The ion bombardment was performed with two different systems, a focused ion beam at the Microstructure laboratory and an ion accelerator at the Tandem laboratory, both at Uppsala University. The main goal of the work was to develop and test a contacting scheme for the graphene flakes that would allow us to perform in-situ I-V measurements during defect insertion. In this respect, the project was a success. The different characterization techniques yielded different types of information. LOM is useful as a first screening to identify the graphene candidates; Raman spectroscopy can provide information on both the flake thickness (mono-layer or multi-layer) and on the defect density, although the latter only qualitatively. The AFM analysis did not give significant results as it could not unambiguously discern any sign of ion impact neither on the graphene flakes nor on the substrate.