Health status and quality of life of elderly persons with severe hemophilia born before the advent of modern replacement therapy

SUMMARY BACKGROUND: More and more people with severe hemophilia reach an old age thanks to an effective treatment. There is no information on the health status and quality of life of elderly people with hemophilia born at a time when replacement therapy was hardly available. METHODS: Italian patients with severe hemophilia, aged >or=65 years and hence born in 1942 or earlier, were compared with elderly men without bleeding disorders matched for age, sex, geography and social status. The following aspects were evaluated: concomitant illness, orthopedic status, physical functioning and cognitive status. Measurements of generic and disease-specific health-related quality of life were also obta…

Bleeding symptoms at disease presentation and prediction of ensuing bleeding in inherited FVII deficiency.

SummaryIndividuals with inherited factor VII (FVII) deficiency display bleeding phenotypes ranging from mild to severe, with 30% of patients having always been asymptomatic (non-bleeding). In 626 FVII-deficient individuals, by analysing data from the International Factor VII (IF7) Registry and the Seven Treatment Evaluation Registry (STER), we determined whether bleeding type at disease presentation and FVII coagulant activity (FVIIc) predict ensuing bleeds. At disease presentation/diagnosis, 272 (43.5%) individuals were non-bleeding, 277 (44.2%) had minor bleeds, and 77 (12.3%) had major bleeds. During a median nine-year index period (IP) observation, 87.9% of non-bleeding individuals at p…

Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis.

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 ma…

Rules-based HIV-1 genotypic resistance interpretation systems predict 8 week and 24 week virological antiretroviral treatment outcome and benefit from drug potency weighting

Objectives: To test retrospectively the ability of four freely available rules-based expert systems to predict short- and medium-term virological outcome following an antiretroviral treatment switch in pre-treated HIV-1 patients. Methods: The HIV-1 genotype interpretation systems (GISs) HIVdb, ANRS, Rega and AntiRetroScan were tested for their accuracy in predicting response to highly active antiretroviral therapy using 8 week (n = 765) and 24 week (n = 634) follow-up standardized treatment change episodes extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) database. A genotypic sensitivity score (GSS) was derived for each genotype-treatment pair for the different GI…

Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Background and objectives: Guidelines indicate a plasma HIV-1 RNA load of 500-1000 copies/mL as the minimal threshold for antiretroviral drug resistance testing. Resistance testing at lower viral load levels may be useful to guide timely treatment switches, although data on the clinical utility of this remain limited. We report here the influence of viral load levels on the probability of detecting drug resistance mutations (DRMs) and other mutations by routine genotypic testing in a large multicentre European cohort, with a focus on tests performed at a viral load <1000 copies/mL. Methods: A total of 16511 HIV-1 reverse transcriptase and protease sequences from 11492 treatment-experienced …

Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolonged pharmacodynamic effect.

Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolonged pharmacodynamic effect -

A novel methodology for large-scale phylogeny partition

Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny …

Declining Prevalence of HIV-1 Drug Resistance in Antiretroviral Treatment-exposed Individuals in Western Europe

HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis. © 2013 The Author.

Low Rate of Virological Failure and Maintenance of Susceptibility to HIV-1 Protease Inhibitors with First-Line Lopinavir/Ritonavir-Based Antiretroviral Treatment in Clinical Practice

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after …

Health-related quality of life and psychological well-being in elderly patients with haemophilia

Many persons with severe haemophilia reach seniority thanks to effective treatment. There is no information on health-related quality of life (HRQoL) of these patients, who had lived for many years when regular replacement therapy was unavailable. Italian patients with severe haemophilia aged ≥65 years born in the 1940s or earlier were compared with men without bleeding disorders matched for age and geography. HRQoL was assessed via generic and disease-specific questionnaires. Potential associations with concomitant illnesses, orthopaedic status, physical functioning, cognitive status and depression were evaluated. In addition, the newly adapted HRQoL questionnaire specific for elderly pers…

Pharmacokinetic of Factor VII

No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy

An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression 50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analy…