Efficacy and safety of glecaprevir/pibrentasvir in treatment-naïve adults with chronic hepatitis C virus genotypes 1–6 in Brazil

Introduction and objectives: Glecaprevir/pibrentasvir is a highly effective and well tolerated treatment for hepatitis C infection. Brazilian patients were not included in the original development studies for glecaprevir/pibrentasvir. This study aimed to assess safety and efficacy of glecaprevir/pibrentasvir in treatment-naïve Brazilian adults without cirrhosis or with compensated cirrhosis. Patients and methods: EXPEDITION-3 was a Phase 3, open-label, multicenter study in treatment-naïve Brazilian adults with hepatitis C infection genotype 1–6. Patients without cirrhosis (F2 or F3) or with compensated cirrhosis (F4) received 8 or 12 weeks of glecaprevir/pibrentasvir, respectively. The primary efficacy endpoint was the rate of sustained virologic response at post-treatment Week 12. Secondary endpoints were on-treatment virologic failure and relapse rates. Baseline polymorphisms were assessed in NS3 and NS5A. Adverse events and laboratory abnormalities were monitored. Results: 100 patients were enrolled, 75 received 8 weeks of treatment and 25 received 12 weeks; all patients completed treatment. Overall sustained virologic response at post-treatment Week 12 rate was high (98.0%; 98/100; 95% confidence interval: 93.0–99.4) and remained high regardless of baseline viral or host factors, including demographics, hepatitis C virus RNA levels, polymorphisms in NS3 and/or NS5A, genotype, and relevant comorbidities. 55% of patients reported ≥1 adverse event, the most common beingheadache (18.0%). Four patients reported serious adverse events; none were considered drug related orled to study drug discontinuation. No hepatic decompensations were observed.Conclusions: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilianpatients with hepatitis C infection without cirrhosis and with compensated cirrhosis

Fatores de risco para a infecção pelo virus da AIDS entre usuarios de drogas endovenosas da região de Campinas, São Paulo, Brasil

Orientador : Rogerio de Jesus PedroDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: A importância do uso de drogas injetáveis na transmissão do vírus HIV vem crescendo tanto nos países desenvolvidos quanto nos em desenvolvimento, potencializando a transmissão heterossexual e conseqüentemente a vertical. (...continue)Abstract: The importance of the use of injectable drugs in the transmission of the HIV virus has been increasing in developed countries as well as in the developing ones, increasing the heterosexual transmission and consequently the vertical one. (¿continue)MestradoMestre em Ciências Médica

Infecção pelo virus da hepatite C entre parturientes : soroprevalencia, analise dos fatores de risco, infectividade e transmissão vertical

Orientador: Rogerio de Jesus PedroTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: O estudo realizado no Hospital Universitário da Pontifícia Universidade Católica (PUC) de Campinas entre janeiro de 1994 e julho de 1998 constou de duas partes: a primeira, sobre a soroprevalência do VHC entre parturientes, os fatores de risco envolvidos e o potencial de infectividade entre as mulheres com anti-VHC-EIA positivo, e a segunda, sobre a transmissão vertical do VHC. Na investigação da prevalência dessa infecção, participaram 6.995 mulheres que tiveram o sangue coletado na sala de parto e que responderam a uma entrevista padrão, realizada durante a internação, objetivando a pesquisa de antecedentes epidemiológicos relativos a microorganismos veiculados pelas vias sangüínea e (ou) sexual. Utilizaram-se análises de associação e modelos de regressão múltipla na relação da positividade do RIBA e da presença do RNA-VHC com as variáveis epidemiológicas. A prevalência anti-VHC pelo EIA-3 foi de 1,5% (104/6.995) e de 0,8% após o RIBA-3. Nessa população, obteve-se também a positividade do anti-HIV-EIA de 1,0% e de 0,9% segundo o "Western blot"; a positividade do HBsAg de 0,5% e do anti-HBc de 6,8%; 0,9% de positividade anú-T.pallidum (VDRL e FTA-ABS). Com o teste RT-PCR, pesquisou-se o RNA-VHC em 75 mulheres reativas ao anti- VHC-EIA, e 35 (46,7%) amostras foram positivas. Das 47 amostras com RIBA reagente, 20 (42,6%) apresentaram níveis alterados de ALT, com RNA-VHC em 90% delas, e nas 12 amostras indeterminadas, 2 (16,7%) tinham níveis alterados de ALT, com RNA presente em 50%. No modelo de regressão logística múltipla, as cinco variáveis preditoras da positividade do RIBA, marcador de infecção prévia pelo VHC, foram: uso de bebida alcoólica, transfusão de sangue, pertencer a raça negra, antecedente de DST e anti-HBc positivo. Não foi possível compor esse modelo com a variável uso de drogas injetáveis e VDRL positivo. Repetiu-se a análise multivariada, após controlar as variáveis relativas à transmissão parenteral do VHC, para explorar o potencial da via sexual na transmissão do VHC. Antecedente de DST, presença do anti-HBc, ter ou ter tido parceiro sexual com história de hepatite ou parceiro heterossexual promíscuo foram determinantes da positividade do RIBA. Procurou-se associar os resultados do teste RT-PCR às características do RIBA, aos níveis de ALT, à co-infecção pelo HIV ou VHB e às variáveis epidemiológicas estudadas. Na análise multivariada, as variáveis que estimaram a presença do RNA-VHC foram as interações das bandas cl00-3 - c33c e c22-3 - c33c. Na segunda parte deste estudo, referente à transmissão vertical do VHC, participaram 61 mulheres com anti-VHC-EIA positivo e os respectivos filhos, de 72 partos acompanhados seqüencialmente. Entre o 2° e o 18° mês de vida, coletou-se, no mínimo, uma amostra de sangue. Dessas 72 crianças, 45 tinham mães com RIBA positivo, 13 indeterminado e 14 negativo, sendo 42 delas filhas de mulheres com viremia (39 com RIBA positivo e 03 indeterminado). Dentre os 42 lactentes, incluindo 09 filhos de mães co-infectadas pelo HIV, um apresentou repetidamente o RNA-VHC aos quatro meses de idade, evoluindo com alterações nos níveis de ALT entre o 7º e 11° mês de vida. A positividade da sorologia anti-VHC (EIA e RIBA) desta criança manteve-se até o 18° mês de vida, atendendo ao critério diagnóstico proposto para infecção vertical pelo VHC. A taxa de transmissão foi de 2,4% (01 em 42) e de 3% ao se excluírem as crianças de mulheres co-infectadas pelo HIV (01 em 33). Este estudo demonstrou que a prevalência anti-VHC-EIA entre as mulheres grávidas é superior à dos doadores de sangue do mesmo hospital; que a exposição sexual pode ser um importante fator na disseminação do VHC; e que a transmissão vertical do VHC ocorre, porém, com freqüência baixaAbstract: This study performed at the University Hospital of the Pontifícia Universidade Católica de Campinas (PUC-Campinas) between January of 1994 and July of 1998 was divided into two parts: the first was about the HCV prevalence among parturients, the risk factors involved in it and the infectivity potential among anti HCV-EIA positive women; the second one was about vertical transmission of the HCV. A total of 6995 women have participated in the HCV prevalence study. The women answered a standard questionnaire during their stay in the hospital and had their blood collected in the obstetric center. These two procedures were performed in order to study the epidemiological history related to pathogens of sexual or blood-borne transmission. Analyses of association and models of multiple regression were utilized in association of the RIBA and HCV RNA positivity with the epidemiological variables. The anti-HCV seroprevalence by EIA-3 was 1.5% (104/6995) and after RIBA-3 was 0.8%. It was obtained in this population anti-HIV-EIA seropositivity of 1.0% and 0.9% according to the Western blot; HBsAg positivity of 0.5% and anti-HBc of 6.8%; and 0.9% of the anti T.pallidum positivity (VDRL and FTA-abs). The HCV RNA was studied, utilizing RT-PCR, in 75 anti-HCV-EIA reactive women, resulting in 35 (46,7%) positive samples. Of the 47 RIBA-reactive samples, 20 (42,6%) showed abnormal alanine aminotransferase (ALT) levels with HCV RNA in 90% of them and, of the 12 eterminate samples, 2 (16,7%) had abnormal ALT levels with HCV RNA in 50% of them. In the model of multiple logistic regression, five independent predictors of RIBA positivity, the marker of previous HCV infection, were: alcohol use, blood transfusion, race (blacks), a history of STD and anti-HBc positivity. It was not possible to build this model with the variables - injectable drug use and positive VDRL . The model of multiple logistic regression was repeated, after controlling for parenteral exposure, in order to explore the potential of the sexual via in HCV transmission. A history of STD, anti-HBc positivity and having or having had promiscuous heterosexual partner or sex partner with a history of hepatitis were determinants of RIBA positivity. The results of RT-PCR test were tested in the association with the characteristics of RIBA results, with ALT levels, with HIV or VHB coinfection, and with the epidemiological variables studied. In the multivariate analysis, RNA HCV was estimated by interactions of the C100 - C33c and of the C22-3 - C33c bands. A total of 61 anti-HCV-EIA-positive women and their respective children, of 72 sequentially assisted deliveries, participated in the second part of this study, which was about HCV vertical transmission. Between the 2nd and the 18th month of age, at least oneblood sample was collected from mother-child. Forty-five out of these children had RIBA-positive mothers; 13 had indeterminate RIBA; and 14 had negative RIBA. Forty-two of them were children of women with viremia: 39 had RIBA-positive mothers and 3 indeterminate. Among the 42 infants there were 09 whose mothers were HIV coinfected. From this total of 42, one presented the RNA-HCV repeatedly at the fourth month of age and he also showed abnormal ALT levels between 7° and 11° month of age. Anti-HCV (EIA and RIB A) positivity of this child was kept until the 18th month of live, according to the proposed diagnostic criteria of vertical transmission. The transmission rate was 2.4% (1 in 42) and 3%, being excluded the children of the HIV-coinfected women (1 in 33). This study has demonstrated that anti-HCV-EIA prevalence was higher in pregnant women than in blood donors of the same hospital; that sexual exposure may be an important factor to the spreading of HCV; and that vertical HCV transmission occurs, but with a low frequencyDoutoradoClinica MedicaMestre em Ciências Médica

Intravenous Azithromycin Plus Ceftriaxone Followed by Oral Azithromycin for the Treatment of Inpatients With Community-Acquired Pneumonia: An Open-Label, Non-Comparative Multicenter Trial

Edson Duarte Moreira Junior “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”.Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2017-06-08T16:20:31Z No. of bitstreams: 1 Rubio FG intraveneous azithromycin plus....pdf: 56192 bytes, checksum: 1e7e5951a977bf7d633fed5b19995e47 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2017-06-08T16:41:32Z (GMT) No. of bitstreams: 1 Rubio FG intraveneous azithromycin plus....pdf: 56192 bytes, checksum: 1e7e5951a977bf7d633fed5b19995e47 (MD5)Made available in DSpace on 2017-06-08T16:41:32Z (GMT). No. of bitstreams: 1 Rubio FG intraveneous azithromycin plus....pdf: 56192 bytes, checksum: 1e7e5951a977bf7d633fed5b19995e47 (MD5) Previous issue date: 2008Hospital de Base of FUNFARME. São José do Rio Preto, SP, BrasilNossa Senhora das Graças Hospital. Curitiba, PR, BrasilOtávio de Freitas General Hospital. Recife, PE, BrasilCatholic University of Campinas, Campus II. Department of Infectious Diseases. Campinas, SP, BrasilIrmandade da Santa Casa de Misericórdia of Porto Alegre. Porto Alegre, RS, BrasilUniversity Hospital of Federal University of Juiz de Fora. Juiz de Fora, MG, BrasilIrmandade da Santa Casa de Misericórdia of São Paulo. São Paulo, SP, BrasilNossa Senhora da Conceição Hospital. Porto Alegre, RS, BrasilGeneral Hospital of Itapecerica da Serra. OSS Seconci. Itapecerica da Serra, SP, BrasilGeneral Hospital Roberto Santos. Salvador, BA, BrasilFederal University of São Paulo. São Paulo, SP, BrasilFederal University of Paraná. Clinical Hospital de Clinicas. Curitiba, PR, BrasilSanatorinhos Hospital. OSS. Ação Comunitária. São Paulo, SP, BrasilCommunity-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% – 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% – 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP