Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the ...lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection.
We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis.
Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval CI, 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (
= .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (
= .016).
Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) frequently cause patients with COPD to access the emergency department and have a negative impact on the course of the disease. ...The objectives of our study were: 1) describing the socio-demographic and clinical characteristics, and the clinical management, of patients with AECOPD, when they present to the emergency department; and 2) estimating the costs related to the management of these patients. We conducted a retrospective cohort study in Italy, collecting data on 4396 patients, from 34 centres. Patients had a mean (SD) age of 76,6 (10.6) years, and 61.2% of them where males. >70% of the patients had a moderate to very high comorbidity burden, and heart failure was present in 26.4% of the cohort. The 64.6% of patients were admitted to hospital wards, with a mean (SD) length of stay of 10.8 (9.8) days. The estimated cost per patient was 2617 €. Conclusions: Patients attending the ED for an AECOPD are old and present important comorbidities. The rate of admission is high, and costs are remarkable.
•AECOPDs accounts for 0.5% of ED visits in Italy.•Patients attending the ED for an AECOPD are old and frequently affected by several comorbidities.•The majority of patients are admitted, and costs are high.
Abstract Chronic hepatitis C virus (HCV) infection is a major public health problem at a global level, causing an enormous burden of hepatic and extra-hepatic morbidity and mortality. Treatment of ...chronic HCV (CHC) has been revolutionized in the last few years by the introduction of highly effective and well tolerated direct acting antiviral agents (DAAs) able to achieve >90% rates of sustained virological response (SVR) in many groups of patients, including those previously excluded from interferon-based regimens. For such reason interferon-free regimens are now the treatments of choice for all patients. Successful anti-HCV treatment can stop liver disease progression and can solve the HCV-related extra hepatic manifestations, eventually reducing both liver-related and overall mortality. Together with the rapidly accumulating data about the evolution of treatment landscape, different guidelines from national and international Liver Scientific Societies have been published until today. However, these recommendations may not be applied worldwide as, due to high treatment costs, most of them identify as priority groups only patients with advanced liver disease. Moreover some types of patients pose clinical management problems for which even the guidelines do not always provide useful answers. With the aim of treatment optimization by filling some of the gaps of the current guidelines and addressing the remaining unmet needs in practice, a group of Italian experts, experienced on treatment of HCV infection, met in Stresa in February 2016. The summary of all the considerations arising from this two-day meeting and the final statements are reported in this position paper.
The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the ...virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients.
Observational European cohort collaboration study.
Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95).
The study included 19,968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals.
Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.
Despite a substantial reduction in virological failures following introduction of new potent antiretroviral therapies in the latest years, drug resistance remains a limitation for the control of ...HIV-1 infection. We evaluated trends and correlates of resistance in treatment failing patients in a comprehensive database over a time period of relevant changes in prescription attitudes and treatment guidelines.
We analyzed 6,796 HIV-1 pol sequences from 49 centres stored in the Italian ARCA database during the 2003-2012 period. Patients (n = 5,246) with viremia > 200 copies/mL received a genotypic test while on treatment. Mutations were identified from IAS-USA 2013 tables. Class resistance was evaluated according to antiretroviral regimens in use at failure. Time trends and correlates of resistance were analyzed by Cochran-Armitage test and logistic regression models.
The use of NRTI backbone regimens slightly decreased from 99.7% in 2003-2004 to 97.4% in 2010-2012. NNRTI-based combinations dropped from 46.7% to 24.1%. PI-containing regimens rose from 56.6% to 81.7%, with an increase of boosted PI from 36.5% to 68.9% overtime. In the same reference periods, Resistance to NRTIs, NNRTIs and PIs declined from 79.1% to 40.8%, from 77.8% to 53.8% and from 59.8% to 18.9%, respectively (p < .0001 for all comparisons). Dual NRTI + NNRTI and NRTI + PI resistance decreased from 56.4% to 33.3% and from 36.1% to 10.5%, respectively. Reduced risk of resistance over time periods was confirmed by a multivariate analysis.
Mutations associated with NRTIs, NNRTIs and PIs at treatment failure declined overtime regardless of specific class combinations and epidemiological characteristics of treated population. This is likely due to the improvement of HIV treatment, including both last generation drug combinations and prescription guidelines.
Exacerbations of chronic obstructive pulmonary disease (COPDE) frequently require hospitalizations, may necessitate of invasive mechanical ventilation (IMV), and are associated with a remarkable ...in-hospital mortality. The BAP-65 score is a risk assessment model (RAM) based on simple variables, that has been proposed for the prediction of these adverse outcomes in patients with COPDE. If showed to be accurate, the BAP-65 RAM might be used to guide the patients management, in terms of destination and treatment. We conducted a retrospective, multicentre, chart-review study, on patients attending the ED for a COPDE during 2014. The aim of the study was the validation of the BAP-65 RAM for the prediction of in-hospital death or use of IMV (composite primary outcome). We assessed the discrimination and the prognostic performance of the BAP-65 RAM. We enrolled 2908 patients from 20 centres across Italy. The mean (standard deviation) age was 76 (11) years, and 38% of patients were female. The composite outcome occurred in 5.3% of patients. The AUROC of BAP-65 for the composite outcome was 0.64 (95%CI 0.59–0.68). The sensitivity of BAP-65 score ≥ 4 to predict in-hospital mortality was 44% (95% CI 34%–55%), the specificity was 84% (95% CI 82%–85%), the positive predictive value was 9% (95% CI 6%–12%), and the negative predictive value was 98% (95% CI 97%–98%).
In patients attending Italian EDs with a COPDE, we found that the BAP-65 score did not have sufficient accuracy to stratify patients upon their risk of severe in-hospital outcomes.
•Patients with COPDE are at risk of adverse short-term clinical outcome.•The BAP-65 score has been proposed for the prediction of mortality and use of IMV.•We validated the prognostic performance of the score in the ED setting.•The BAP-65 tool is not sufficiently accurate for risk prediction in ED patients with COPDE.
Abstract Hepatitis C virus (HCV) infection remains one of the main causes of chronic liver disease worldwide. The advent of direct-acting antivirals (DAAs) has significantly improved the course of ...patients with chronic HCV infection (CHC), due to the ability of these drugs to achieve high rates of sustained virological response (SVR). These exceedingly high rates of SVR and the excellent safety data have been confirmed in real life practice. Evolving guidelines have been issued by national and international scientific societies in accordance with the progression of clinical knowledge and the availability of new DAAs. These recommendations, however, may not be applied universally because of delays in drugs reimbursability in different countries and because some National Health Systems identify only patients with advanced disease as a treatment priority. Italy in this regard is a prototype about DAAs treatment of CHC patients. With the aim to assess the Italian treatment experience with DAAs and to respond to unmet needs in treatment optimization of antiviral therapy in specific settings of CHC patients, a group of Italian experts met in Stresa in February 2017. The summary of the considerations arising from this two-day meeting and some statements regarding a few open issues are reported in this position paper.
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