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Sterrantino G.,SOD Malattie Infettive | Zaccarelli M.,Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani | Colao G.,Laboratorio Of Virologia | Baldanti F.,Laboratorio Of Virologia | And 4 more authors.
Infection | Year: 2012

Introduction: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. Results: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. Discussion The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. Conclusion: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon. © Springer-Verlag 2011. Source


Sterrantino G.,SOD Malattie Infettive | Santoro L.,SOD Malattie Infettive | Bartolozzi D.,SOD Malattie Infettive | Trotta M.,SOD Malattie Infettive | Zaccarelli M.,Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Patient Preference and Adherence | Year: 2012

Objective: To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc. Methods: Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self-report questionnaire was filled in. Patients were defined as "nonadherent" if reporting one of the following criteria: <90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence. Results: At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on OD regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The nonadherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34-0.94) and the STR (OR: 0.45, 95% CI: 0.22-0.92) reported lower nonadherence. Efavirenz regimens were also associated with lower nonadherence (OR: 0.42, 95% CI: 0.21-0.83), while atazanavir/ritonavir regimens were associated with higher nonadherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower nonadherence, while a longer time on combined antiretroviral therapy was related to higher nonadherence. Conclusion: STR maintains an advantage in improving adherence with respect to other combined antiretroviral therapies, even though new antiretroviral drugs and drug classes have become available in recent years. © 2012 Sterrantino et al, publisher and licensee Dove Medical Press Ltd. Source


Sterrantino G.,Azienda Ospedaliera Universitaria Careggi | Zaccarelli M.,Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani | Trotta M.,Catholic University of the Sacred Heart | Trotta M.,University of Siena | And 6 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2012

From the Italian Antiretroviral Resistance Cohort Analysis database, 1104 patients starting ritonavir-boosted darunavir-containing regimen were included as follows: 118 subsequently failed treatment at a median of 11 months (interquartile range: 5-20); 3 years failure proportion: 24.6%. HIV Drug Resistance Database and ANRS interpretation algorithms were associated with a progressive risk prediction of virological failure at adjusted Cox. In contrast, Rega algorithm allows to identify a higher number of patients at risk of failure, without losing statistical significance. Four mutations (V32I, I50V, L76V, I84V) were predictive of failure, the hazard ratio progressively increased by detecting 1 (hazard ratio: 2.0, 95% confidence interval: 1.3 to 3.0), 2 (3.6, 2.0 to 6.6), or 3 of them (9.7, 2.8 to 33.5). Copyright © 2012 Lippincott Williams & Wilkins. Source


Pourcel C.,University Paris - Sud | Minandri F.,Third University of Rome | Hauck Y.,University Paris - Sud | D'Arezzo S.,Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani | And 4 more authors.
Journal of Clinical Microbiology | Year: 2011

Acinetobacter baumannii is an important opportunistic pathogen responsible for nosocomial outbreaks, mostly occurring in intensive care units. Due to the multiplicity of infection sources, reliable molecular fingerprinting techniques are needed to establish epidemiological correlations among A. baumannii isolates. Multiple-locus variable-number tandem-repeat analysis (MLVA) has proven to be a fast, reliable, and costeffective typing method for several bacterial species. In this study, an MLVA assay compatible with simple PCR- and agarose gel-based electrophoresis steps as well as with high-throughput automated methods was developed for A. baumannii typing. Preliminarily, 10 potential polymorphic variable-number tandem repeats (VNTRs) were identified upon bioinformatic screening of six annotated genome sequences of A. baumannii. A collection of 7 reference strains plus 18 well-characterized isolates, including unique types and representatives of the three international A. baumannii lineages, was then evaluated in a two-center study aimed at validating the MLVA assay and comparing it with other genotyping assays, namely, macrorestriction analysis with pulsed-field gel electrophoresis (PFGE) and PCR-based sequence group (SG) profiling. The results showed that MLVA can discriminate between isolates with identical PFGE types and SG profiles. A panel of eight VNTR markers was selected, all showing the ability to be amplified and good amounts of polymorphism in the majority of strains. Independently generated MLVA profiles, composed of an ordered string of allele numbers corresponding to the number of repeats at each VNTR locus, were concordant between centers. Typeability, reproducibility, stability, discriminatory power, and epidemiological concordance were excellent. A database containing information and MLVA profiles for several A. baumannii strains is available from http://mlva.u-psud.fr/. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source


Pezzotti P.,Istituto Superiore di Sanita | Pozzato S.,Laziosanita Agenzia di Sanita Pubblica | Ferroni E.,Laziosanita Agenzia di Sanita Pubblica | Mazzocato V.,Catholic University of the Sacred Heart | And 6 more authors.
Epidemiology Biostatistics and Public Health | Year: 2015

Background: To estimate patient and health care delays in the ,diagnosis of pulmonary tuberculosis (PTB) and evaluate associated factors. Methods: PTB incident cases ≥18 years diagnosed between September 2010 and September 2011 in the Lazio region; information on symptoms,date of onset, health professional contacts, diagnostic exams performed and drugs prescribed before diagnosis were collected through a standardized questionnaire. The total delay (TD) was divided into patient delay (PD: from onset of symptoms to first contact with healthcare services) and health system delay (HSD: from first contact to diagnosis). Results: Two hundred seventy-eight cases were evaluated. Median PD,HSD and TD were 31, 15 and 77.5 days, respectively. The median PD, HSD and TD were significantly lower in foreign-born patients (26, 10.5 and 63.5 vs. 45, 36 and 100 days, respectively). Other factors independently associated with longer delay were: absence of fever and presence of weight loss for PD; prior unspecific treatment, absence of cough, consultation with a general practitioner, visit atan outpatient clinic and a PD <30 days for HSD. ConclusionS: In Italy, the delay ofTB diagnosis is similar to that estimated in other European countries. Results indicate that actions aimed to reduce diagnostic delay should be primarily addressed to Italian patients © 2015, Prex S.p.A. All rights reserved. Source

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