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

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

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

The Implementation Of A Surgical Antibiotic Prophylaxis Program: The Pivotal Contribution Of The Hospital Pharmacy.

Although surgical site infection rates have decreased with the prophylactic use of antibiotics, the inappropriateness of surgical antibiotic prophylaxis is still a worldwide problem. Various strategies have been used to address this problem. This study describes the implementation of a perioperative antibiotic prophylaxis protocol that emphasizes the contribution of the pharmacist. A descriptive study design was used to evaluate the impact of the protocol on the appropriateness of prophylaxis in a private university hospital. The surgical antibiotic prophylaxis of all surgeries was evaluated for 1 month before and 1 month after the implementation of the protocol. The appropriateness of the indication for prophylaxis rose from 56.4% to 100% and that of the postoperative maintenance prophylactic antibiotics rose from 21.9% to 95.7%. The cost of the perioperative antibiotic prophylaxis per surgery decreased 40.5%. The implementation of a cost-effective perioperative antibiotic prophylaxis protocol was the result of a multidisciplinary effort. The hospital pharmacist participated in education activities as part of the discussion groups on the perioperative antibiotic prophylaxis protocol that involved all participants and in managerial actions that optimized the process of ordering, dispensing, administering, and documenting the perioperative antibiotic prophylaxis.3049-5

Primary Antiretroviral Drug Resistance among HIV Type 1-Infected Individuals in Brazil

Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) has been documented in all countries that have surveyed for it and may result in an unfavorable response to therapy. the prevalence and characteristics of individuals with transmitted resistance to antiretroviral drugs have been scarcely described in Brazil. We performed antiretroviral resistance testing prior to initiation of therapy in 400 subjects enrolled from 20 centers in 13 Brazilian cities between March and September 2007. Genotyping was conducted using PCR-amplified HIV pol products by automated sequencing, and genotype interpretation was done according to the IAS-USA consensus. of 400 eligible participants, 387 (95.8%) were successfully tested. Seven percent of antiretroviral-naive patients carried viruses with one or more major mutation associated with drug resistance. the prevalence of these mutations was 1.0% for protease inhibitors, 4.4% for nonnucleoside reverse transcriptase inhibitors, and 1.3% for nucleoside reverse transcriptase inhibitors. the frequency of multidrug resistance among the resistant strains was 13.6%. Among subjects infected with drug-resistant virus, the majority were infected with subtype B viruses (91%). Subjects from the city of São Paulo had higher transmitted resistance mutations compared to the rest of the country. Reporting a partner taking antiretroviral medications was associated with a higher chance of harboring HIV variants with major drug resistance mutations [odds ratio = 2.57 (95% confidence interval, 1.07-6.16); p = 0.014].Resistance testing in drug-naive individuals identified 7% of subjects with mutations associated with reduced susceptibility to antiretroviral drugs. Continued surveillance of drug-resistant HIV-1 in Brazil is warranted when guidelines for HIV prophylaxis and treatment are updated. Resistance testing among drug-naive patients prior to treatment initiation should be considered, mainly directed at subjects whose partners are already on antiretroviral therapy.Laboratorio Pfizer do BrasilUniv Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, BrazilHosp Univ Prof Edgard Santos, Salvador, BA, BrazilPontificia Univ Catolica, Hosp & Maternidade Celso Pierro, Campinas, SP, BrazilHosp Heliopolis, São Paulo, BrazilInst Infectol Emilio Ribas, São Paulo, BrazilProjeto Praca Onze, Rio de Janeiro, BrazilCRT AIDS, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniv Estadual Campinas, Campinas, SP, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin ± amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial

Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after ≥ 24 weeks of treatment with conventional interferon plus ribavirin.Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (40KD) 180 μg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/ day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin).Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 lU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin.Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting