Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Anticorpos anti-VIH1 e VIH2 em doentes com Tuberculose. Experiência de um trabalho realizado ao longo de 3 anos nas regiões de Lisboa, Barreiro e Santarém

ABSTRACTSettingPatients with active tuberculosis.ObjectiveTo evaluate the rates of anti-HIV1 and anti-HIV2 antibodies in patients with active Tuberculosis.DesignAnti-HIV antibodies, were searched by ELISA and confirmed by Western blot.ResultsWe studied 767 patients (479 men and 288 women); 671 of them were caucasian, 76 black and 20 from other races. Eighteen of them were intravenous-drug users (IVDU), 35 had been transfused, 630 were heterosexual and in 121 we didn’t obtain data about sexual behaviour; 153 sojourned in Africa for different periods of time; 541 patients (70.5%) had pulmonary tuberculosis, 164 (21.4%) had extrapulmonary tuberculosis, 44 (5,7%) patients presented pulmonary and extrapulmonary tuberculosis and 18 (2.3%) had primary tuberculosis. Fourteen (1.8%) patients bad anti-HIV antibodies: 10 HIV1 and 4 HIV2; all seropositive were heterosexual, one being IVDU; 5 had pulmonary tuberculosis and 9 had extra-pulmonary tuberculosis (including all 4 cases with HIV2).ConclusionsWe found a rate in our population of 1.8% particularly in black patients (3.9%); serum positivity was more frequent in patients with extrapulmonary tuberculosis particularly in HIV2 patients. We advise for systematic screening

Qualidade da carne de marreco pequim branco (Anas Platyrhynchos platyrhynchos L. 1758) comparado a frango de corte Meat quality in white peking mallard (Anas Platyrhynchos platyrhynchos L. 1758 ) compared to broiler chicken

O total de 20 carcaças resfriadas (10 Marrecos Pequim Branco e 10 de frangos de corte) foi submetido às análises de composição centesimal, colesterol, cor (sistema CIE L*a*b*), perda de peso por cozimento (PPC) e força de cisalhamento (FC). A carne de marreco apresenta (P<0,05) menos umidade (71,77 e 74,53 %), do que a carne de frango (74,73 e 76,07 %). Quando comparados os cortes, o peito mostrou (P<0,05) médias mais elevadas de umidade e proteína, do que no corte perna. A carne de marreco mostra (P<0,05) luminosidade mais baixa (37,59 e 35,75) e maior teor de vermelho (18,48 a 20,67), do que a luminosidade (40,98 e 45,18) e o teor de vermelho (10,02 e 5,52) observado em frangos. A FC foi (P<0,05) mais elevada (4,90 kgf) em peito de marrecos, do que em peito de frango (2,63 kgf). A carne de Marreco Pequim Branco é mais escura e com vermelho mais intenso do que carne de frango de corte. Embora menos macia do que a carne de frango, a carne de marreco é considerada macia.<br>Twenty refrigerated carcasses (10 Peking mallard and 10 broiler chicken) were submitted to analyses of chemical composition, cholesterol, colour (CIE L*a*b* system), weight loss by cooking (PPC) and shear force (FC). Mallard meat had lower (P<0.05) humidity in both leg and breast (71.77 and 74.53%, respectively) when compared with chicken meat (74.73 and 76.07%, respectively). When different cuts were compared, the breast had a higher (P<0.05) humidity and protein content than the leg in both species. Mallard leg and breast had lower (P<0.05) lightness (37.59 and 35.75, respectively) and higher red content (18.48 and 20.67, respectively), than the lightness (40.98 and 45.18, respectively) and red content (10.02 and 5.52, respectively) observed in chicken. The FC was higher (P<0.05) in mallard breast (4.90 kgf) than in chicken breast (2.63 kgf). Meat from White Peking mallard is darker and with a stronger red pigment than meat from broiler chicken. Even though it is less tender than meat from broiler chicken, mallard meat still has an acceptable tenderness

Characterization of a large cluster of HIV-1 A1 infections detected in Portugal and connected to several Western European countries

HIV-1 subtypes associate with differences in transmission and disease progression. Thus, the existence of geographic hotspots of subtype diversity deepens the complexity of HIV-1/AIDS control. The already high subtype diversity in Portugal seems to be increasing due to infections with sub-subtype A1 virus. We performed phylogenetic analysis of 65 A1 sequences newly obtained from 14 Portuguese hospitals and 425 closely related database sequences. 80% of the A1 Portuguese isolates gathered in a main phylogenetic clade (MA1). Six transmission clusters were identified in MA1, encompassing isolates from Portugal, Spain, France, and United Kingdom. The most common transmission route identified was men who have sex with men. The origin of the MA1 was linked to Greece, with the first introduction to Portugal dating back to 1996 (95% HPD: 1993.6-1999.2). Individuals infected with MA1 virus revealed lower viral loads and higher CD4+ T-cell counts in comparison with those infected by subtype B. The expanding A1 clusters in Portugal are connected to other European countries and share a recent common ancestor with the Greek A1 outbreak. The recent expansion of this HIV-1 subtype might be related to a slower disease progression leading to a population level delay in its diagnostic.Supported by FEDER, COMPETE, and FCT by the projects NORTE-01-0145-FEDER-000013, POCI-01-0145-FEDER-007038 and IF/00474/2014; FCT PhD scholarship PDE/BDE/113599/2015; FCT contract FCT IF/00474/2014; European Funds through grant BEST HOPE (project funded through HIVERA, grant 249697) and by FCT PTDC/DTP-EPI/7066/2014. Global Health and Tropical Medicine Center are funded through FCT (UID/Multi/04413/2013). We would like to acknowledge all the patients and health care professionals from the Portuguese hospitals that contributed in some way to this study

Data_Sheet_1_Determinants of HIV late presentation among men who have sex with men in Portugal (2014–2019): who’s being left behind?.docx

IntroductionHIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019.MethodsWe included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP).ResultsThe median age was 31 years, 51% had a current income between 501–1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP.ConclusionOur study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.</p

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Núcleos de Ensino da Unesp: artigos 2007

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq