Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.Universidade Estadual Paulista (UNESP) Botucatu School of MedicineUniversidade Federal do Rio de JaneiroUniversidade Estadual de CampinasUniversidade Federal de São Paulo (UNIFESP)Pontificia Universidade Catolica de São PauloUNIFESPSciEL

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10;

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%,

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment:interim analysis from a phase II clinical trial

BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV(+) individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4(+) and CD8(+) T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4(+) and CD8(+) T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4(+) T-cells. The number of candidates that increased in vitro the cytokine levels in CD4(+) and CD8(+) T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829, posted November 11th, 2016) SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-021-00426-z

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

ABSTRACT Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10; p<0.001) and occurrence of liver cirrhosis (PR 2.06; 95% CI 1.11-3.83; p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups

Accuracy of anti HIV-1/2 immunoglobulim G (IgG) detection by a rapid test (Dot-ELISA) in oral fluid of HIV positive/aids patients and voluntary blood donors

A sorologia como metodo de identificacao da infeccao pelo Virus da imunodefiCiência Humana (HIV) e da Sindrome da imunodefiCiência Adquirida (SIDA/aids) tem sido, amplamente usada desde 1985, tanto para o diagnostico clinico, quanto para inqueritos epidemiologicos e triagens sorologicas necessarias em bancos de sangue. Recentemente, vem sendo desenvolvidas tecnicas de diagnostico sorologico rapido, em urina e fluido oral, como alternativa para triagem na deteccao de anticorpos anti-HIV. Varios estudos vem comprovando sua acuracia. O objetivo deste estudo foi avaliar a sensibilidade, especificidade, acuracia, valor preditivo positivo (VPP) e valor preditivo negativo (VPN) do teste de immunoComb II HIV 1&2 Silva© da Orgenics (Dot- ELISA) quando comparado com a sorologia de rotina (ELISA e Western blot)de pacientes HIV positivos/aids, recebendo ou nao tratamento anti-retroviral, em diferentes estagios de evolucao da doenca e individuos, sabidamente, HIV negativos pelo ELISA serico (doadores de sangue). Para a realizacao do estudo foram avaliados 87 pacientes HIV positivos/aids e 5 pacientes HIV negativos (com comportamento de risco) atendidos no Centro de Controle de DefiCiências imunologicas (CCDI) e 98 doadores voluntarios de sangue do Hemocentro da Escola Paulista de Medicina/Universidade Federal de São Paulo (EPM - UNIFESP). A sensibilidade do Dot-ELISA em fluido oral foi de 100 por cento (IC 95 por cento; 80,07-10O por cento), a especificidade de 97,08 por cento (IC 95 por cento; 93,83-1OO por cento) , o valor preditivo positivo de 96,66 por cento(IC 95 por cento; 93,15-100 por cento) , valor preditivo negativo de 100 por cento(IC 95 por cento; 81,41-100 por cento) e acuracia 98,42 por cento (IC 95 por cento; 98,26-98,58 por cento). Este metodo se mostrou altamente aceitavel pelos pacientes, em relacao a coleta de sangue, e de facil realizacao. O teste em questao, nesta casuistica, foi altamente sensivel e especifico tornando-se util, principalmente, em inqueritos epidemiologicos e triagem, entre outras indicacoes. Para realizacao do diagnostico, os resultados positivos demandam um teste confirmatorio com especificidade mais altaBV UNIFESP: Teses e dissertaçõe

Response predictors to treatment with pegylated interferon in chronic hepatitis B

The clinical and epidemiological importance of chronic B hepatitis is currently unquestionable as a cause of end-stage liver disease and hepatocellular carcinoma. Recently, predictors of treatment response of this disease have been studied, both before and during the course of medication. Therapy stopping rules have been proposed, which may be useful in patients presenting poor treatment tolerance. This review discusses the treatment response predictors usefulness, with emphasis on ALT, quantitative HBsAg and HBeAg, quantitative HBV-DNA and HBV genotyp

INFECÇÃO DE FÍSTULA ARTERIOVENOSA POR CANDIDA PARAPSILOSIS: UM RELATO DE CASO

Intercorrências infecciosas são a segunda causa de morbimortalidade, depois de doenças cardiovasculares em pacientes em hemodiálise crônica. Taxas de infecção de acesso vascular permanente para hemodiálise (incluindo Fístula Arteriovenosa (FAV) com e sem enxerto artificial) variam de 11% a 35%, sendo os patógenos mais comuns Staphylococcus spp., gram-negativos e Enterococcus. Infecções fúngicas são raras e a estratégia de tratamento ainda não é definida. O caso em questão trata-se de paciente feminina de 37 anos com história de lúpus eritematoso sistêmico, a qual realizou transplante renal com posterior perda de função do enxerto e retorno à hemodiálise. A paciente vinha em uso de Cateter Venoso Ventral (CVC) de longa permanência em veia jugular interna direita e possuía FAV recentemente confeccionada em membro superior direito, sem utilização prévia, com trombose parcial na Ultrassonografia (USG) da admissão. A paciente inicia episódios de febre e hipotensão durante hemodiálise refratários à antibioticoterapia empírica em clínica de referência há cerca de 2 meses da entrada em nosso serviço para tratamento de possível infecção relacionada ao CVC. Foi identificada Candida parapsilosis em hemocultura de CVC e periféricas. Em seguida, foi iniciado tratamento antifúngico, inicialmente com micafungina, retirado CVC e realizado rastreio com ecocardiograma transesofágico e avaliação oftalmológica, sem evidências de acometimento. No entanto, a paciente persistiu com hemoculturas positivas para Candida do complexo parapsilosis por cerca de 23 dias, sempre sensíveis a todas as classes de antifúngicos. Diante da persistência da candidemia, paciente fez uso prolongado de anfotericina formulação lipídica, repetidos ecocardiogramas, sem evidências de endocardite, e fundoscopias, sem alterações, além de investigação radiológica que não demonstrou presença de focos profundos. Em avaliação de USG da FAV, foram identificados focos vegetantes onde anteriormente havia trombose dos vasos. Frente a isto, atribuiu-se à FAV a causa da candidemia persistente e foi indicado seu desligamento e remoção. A paciente evolui afebril, com hemoculturas negativas e transiciona para antifúngico de manutenção via oral. Apesar de poucos casos relatados, a infecção de FAV por especies de Candida é uma complicação que deve ser investigada na persistência de candidemia nesta população. Este caso, juntamente com demais na literatura sugere que a remoção da FAV é parte fundamental do tratamento