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 being headache (18.0%). Four patients reported serious adverse events; none were considered drug related or led to study drug discontinuation. No hepatic decompensations were observed. CONCLUSIONS: Glecaprevir/pibrentasvir was effective and well tolerated in treatment-naïve Brazilian patients with hepatitis C infection without cirrhosis and with compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03219216.

Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis.

INTRODUCTION AND AIM: Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. MATERIAL AND METHODS: All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12). RESULTS: The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event. DISCUSSION: The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).

Effect of HIV infection in the micronuclei frequency on the oral mucosa.

BACKGROUND: The genotoxic impact of HIV infection on the oral cavity malignancies is unknown. The aim of this study was to evaluate the effect of HIV infection in micronucleus (MN) frequency on the oral mucosa of HIV+ patients and establish a relationship with early cytogenetic changes in oral carcinogenesis. METHODS: Thirty HIV+ individuals who are under highly active antiretroviral therapy (HAART) and 30 non-HIV patients were evaluated. Two smears were taken from the lateral border of the tongue and mouth floor and stained by Feulgen. The frequency of MN was examined in 3000 cells per subject under common microscopy. RESULTS: MN analysis showed no significant difference between groups by Mann-Whitney U-test for total MNs (P = 0.178). The presence of single MN was greater in control group with statistical significance (P = 0.009), while in HIV group, multiple MNs were exhibited in higher mean. CONCLUSIONS: HIV patients under HAART therapy and low viral load values showed higher frequency of multiple MNs, which, although not statistically significant, may be caused by the action of the Vpr gene, an accessory gene of HIV. These results corroborate the theory of HIV infection cytogenetic damage.

Cytological and cytomorphometric evaluation of the oral mucosa in HIV-infected patients undergoing antiretroviral therapy.

BACKGROUND: To evaluate HIV infection-induced alterations in the oral mucosa by comparing inflammation, cell maturation, and cytomorphometric changes in oral mucosal cells between HIV-infected patients undergoing highly active antiretroviral therapy (HAART) and non-HIV-infected patients. METHODS: Thirty HIV-infected patients undergoing HAART and 30 non-HIV-infected patients were studied. Four smears were obtained from the lateral border of the tongue and floor of the mouth with a cytobrush. One sample was stained by the Papanicolaou technique, and three samples were processed for Feulgen staining. Papanicolaou-stained smears were analyzed by light microscopy, and the cytoplasmic (CA) and nuclear (NA) area were measured with the Software AxioVision 4.7. RESULTS: The Wilcoxon signed-rank test showed a significant difference in intermediate epithelial cell types between the HIV-infected and non-HIV-infected groups (P=.005). However, this difference was not observed for superficial epithelial cell types with (P=.672) and without a nucleus (P=.069). Comparative analysis revealed no significant difference in CA (P=.604), NA (P=.298) or NA/CA (P=.456) between the HIV-infected and non-HIV-infected groups. Keratohyalin granules were more frequent in the non-HIV-infected group (P=.0001). CONCLUSIONS: The results showed alterations in cell maturation in HIV-infected patients undergoing HAART with undetectable viral load, but no morphometric changes were observed.

Post COVID-19 Disseminated Mucormycosis in a 55-year-old patient in Western Amazon: Case report

A feared fungal disease surprised and became a warning to severe cases of COVID-19, especially to health professionals involved with the pandemic. Designated as black fungus for public health services in India, where reported data reflects an increase of more than eighty times the expected increase for Rhizopus among the communities. The disease has become even more worrisome due to the high mortality already established as an opportunistic infection, coupled with the reserved prognosis for all those infected and hospitalised by the SARS-CoV-2 severity criteria. This patient, who was submitted to corticosteroid therapy, in an excessive dose, therefore immunosuppressive, developed a severe, disseminated clinical form. It was verified the progression of the lesions and thus the high risk of trans- surgical lethality, or, also, by the insufficiency of conduct in removing the lesions to their satisfaction. Thus, the therapeutic option is the associated use of micafungin, liposomal amphotericin B and isavuconazole for the regressive phase. The patient remains hospitalised with progressive and discrete improvement. Until the opportunity of reevaluation of the surgery by the interspecialty collaboration.

Uma temida doença fúngica surpreendeu e se tornou um alerta para casos graves de COVID-19, principalmente aos profissionais de saúde envolvidos com a pandemia. Designado como fungo preto para serviços de saúde pública na Índia, onde os dados relatados refletem um aumento de mais de oitenta vezes o aumento esperado para Rhizopus entre as comunidades. A doença tornou-se ainda mais preocupante devido à alta mortalidade já estabelecida como infecção oportunista, aliada ao prognóstico reservado para todos os infectados e internados pelos critérios de gravidade do SARS-CoV-2. Esse paciente, que foi submetido à corticoterapia, em dose excessiva, portanto imunossupressora, desenvolveu uma forma clínica grave e disseminada. Verificou-se a progressão das lesões e, portanto, o alto risco de letalidade transcirúrgica, ou, ainda, pela insuficiência de conduta na remoção das lesões a contento. Assim, a opção terapêutica é o uso associado de micafungina, anfotericina B lipossomal e isavuconazol para a fase regressiva. O paciente permanece internado com melhora progressiva e discreta. Até a oportunidade de reavaliação da cirurgia pela colaboração interespecialista.

Does the change on gastrointestinal tract microbiome affects host?

During the past decade, studies on the composition of human microbiota and its relation to the host became one of the most explored subjects of the medical literature. The development of high-throughput molecular technologies allowed a deeper characterization of human microbiota and a better understanding of its relationship with health and disease. Changes in human habits including wide use of antimicrobials can result in dysregulation of host-microbiome homeostasis, with multiple consequences. The purpose of this review is to highlight the most important evidence in the literature of host-microbiome interactions and illustrate how these intriguing relations may lead to new treatment and prevention strategies.

Safety and immunovirologic outcomes with maraviroc combination regimens in patients with a history of past treatment failures and virologic resistance in Brazil: an open-label, multicenter phase 3b study.

Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, experience in regimens containing newer antiretroviral agents is limited. The primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. Of 638 patients screened, 206 were treated and 125 completed the study. Approximately 70% were male; the mean age was 43.2 years. Most patients (65.0%) received an OBT combination of protease inhibitor plus nucleoside reverse transcriptase inhibitor. Adverse event (AE) and treatment-related AE incidence was 91.3% and 36.9%, respectively. The most common AEs were diarrhea, nasopharyngitis, and headache. Serious AEs and treatment-related serious AEs occurred in 16.5% and 4.4% of patients. Only eight patients (3.9%) discontinued due to AEs. Few AIDS-defining events were observed (4.9%). The proportion of patients with viral load <400 copies/ml increased from 2.4% at baseline to 43.9% at week 8, remaining >40% until week 48. At the end of treatment, 26.7% of patients had a viral load <400 copies/ml. Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/µl. In conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.

Clinical and microbiological characterization of KPC-producing Klebsiella pneumoniae infections in Brazil.

In 2008 isolates of KPC-producing Klebsiella pneumoniae (KPC-KPN) were detected for the first time at Hospital Heliópolis, São Paulo, Brazil. The aim of this study was to characterize the clinical and microbiological outcomes of infections caused by KPC-KPN. A historical cohort of patients from whom KPC-KPN strains were isolated was performed. Isolates were identified as resistant to ertapenem by automated broth microdilution system and screened as carbapenemase producers by the modified Hodge test. The beta-lactamase resistance gene blaKPC was detected by PCR. The genetic relatedness of isolates was determined by PFGE. The study provides early clinical experience in treating KPC-KPN infections in a Brazilian tertiary center.

Vacina da gripe para prevenção de doença cardiovascular / Influenza vaccine for the prevention of cardiovascular disease

O risco para resultados adversos cardiovascularesaumenta na presença de infeccções semelhantes àinfluenza (influenza-like), e a vacinação contra a gripe poderiamelhorar estes desfechos cardiovasculares.Objetivos: Avaliar os potenciais benefícios da vacinaçãopara a prevenção primária e secundária da doença cardiovascular.Esta é uma atualização da revisão sistemática Cochranepublicada em 2008...

Tratamento cirúrgico de 510 pacientes portadores de lipodistrofias secundárias ao uso de antirretrovirais / Surgical treatment of 510 patients with highly active antiretroviral therapy-associated lipodystrophy

INTRODUÇÃO O tratamento da Síndrome da Imunodeficiência Adquirida vem sofrendo importantes avanços desde a introdução da terapia antirretroviral altamente ativa, conhecida como HAART (high active antirretroviral therapy). Este tratamento levou à eliminação do vírus na corrente sanguínea e ao aumento na sobrevida, entretanto alterações metabólicas e estruturais tornaram-se evidentes. Uma dessas alterações é a redistribuição de gordura corpórea, também denominada lipodistrofia. Com uma das maiores casuísticas mundiais, o objetivo deste trabalho é demonstrar algumas das alternativas cirúrgicas, bem como os resultados obtidos na tentativa de minimizar o impacto da lipodistrofia. MÉTODO: No período de julho de 2005 a julho de 2013, 510 pacientes portadores de lipodistrofia secundária ao uso de HAART foram operados pela Clínica de Cirurgia Plástica do Hospital Heliópolis. Todos esses pacientes foram submetidos à prévia avaliação clínica e imunológica, sob auxílio da equipe de Infectologia. O presente trabalho foi aprovado pelo Comitê de Ética em Pesquisa da Fundação do ABC. RESULTADO: Dentre os 510 pacientes, 335 eram do sexo feminino e 175 do sexo masculino, com idades variando entre 16 e 74 anos. Quanto aos procedimentos, destacou-se lipoaspiração da giba e dorso, com 199 casos. Quanto à resposta estimulada através de questionário subjetivo, observou-se elevado grau de satisfação, aumento significativo da autoestima e maior adesão ao tratamento antirretroviral. CONCLUSÃO: A correção cirúrgica da lipodistrofia corporal comprovadamente melhora o aspecto estético do paciente que faz uso da HAART; porém, o efeito psicológico e social é ainda mais importante, elevando a autoestima, com diminuição dos estigmas, e proporcionando uma maior adesão ao tratamento antirretroviral.

INTRODUCTION The treatment of acquired immunodeficiency syndrome has undergone important advances since the introduction of highly active antiretroviral therapy (HAART). This treatment led to the elimination of the virus in the bloodstream and increased survival; however, metabolic and structural changes became evident. One of these changes is lipodystrophy, the redistribution of body fat. With one of the largest samples worldwide, the aim of this work was to present some of the various surgical alternatives as well as the results obtained for minimizing the impact of lipodystrophy. METHOD: From July 2005 to July 2013, 510 patients with HAART-associated lipodystrophy underwent surgery in the Clinic of Plastic Surgery, Heliópolis Hospital. All patients submitted to prior clinical and immunological assessments made with the aid of the infectious diseases team. The present study was approved by the Research Ethics Committee of the ABC Foundation. RESULTS: The 510 patients included 335 women and 175 men with an age range of 16-74 years. Liposuction of the cervicodorsal fat pad (buffalo hump) was predominant (199 cases). With regard to the response stimulated through a subjective questionnaire, a high degree of satisfaction was observed with a significant increase in self-esteem and greater adherence to antiretroviral treatment. CONCLUSION: The surgical correction of body lipodystrophy demonstrably improves the aesthetics of patients using HAART; however, its psychological and social effects are even more important since self-esteem increases and stigma decreases, which leads to better adherence to antiretroviral treatment.

Does the change on gastrointestinal tract microbiome affects host?

During the past decade, studies on the composition of human microbiota and its relation to the host became one of the most explored subjects of the medical literature. The development of high-throughput molecular technologies allowed a deeper characterization of human microbiota and a better understanding of its relationship with health and disease. Changes in human habits including wide use of antimicrobials can result in dysregulation of host–microbiome homeostasis, with multiple consequences. The purpose of this review is to highlight the most important evidence in the literature of host–microbiome interactions and illustrate how these intriguing relations may lead to new treatment and prevention strategies.

Case report: severe, symptomatic hypomagnesemia in acute leptospirosis.

We report a case of severe hypomagnesemia in non-oliguric acute renal failure caused by leptospirosis that required large doses of magnesium replacement during the acute phase of disease. Biochemical studies confirmed kidney-related magnesium wasting and the mechanisms of this defect are discussed. Magnesium imbalance with its attendant clinical complications occurs in leptospirosis and should be monitored and treated aggressively in cases of leptospirosis-induced non-oliguric acute kidney injury.

Clinical and microbiological characterization of KPC-producing Klebsiella pneumoniae infections in Brazil

In 2008 isolates of KPC-producing Klebsiella pneumoniae (KPC-KPN) were detected for the first time at Hospital Heliópolis, São Paulo, Brazil. The aim of this study was to characterize the clinical and microbiological outcomes of infections caused by KPC-KPN. A historical cohort of patients from whom KPC-KPN strains were isolated was performed. Isolates were identified as resistant to ertapenem by automated broth microdilution system and screened as carbapenemase producers by the modified Hodge test. The beta-lactamase resistance gene blaKPC was detected by PCR. The genetic relatedness of isolates was determined by PFGE. The study provides early clinical experience in treating KPC-KPN infections in a Brazilian tertiary center.

Infeccão pulmonar tripla em paciente gravemente imunocomprometido por AIDS: relato de caso / Triple pulmonary infection in a severely immunocompromised AIDS patient: a case report

Os autores relatam um caso de paciente do sexo masculino, 38 anos de idade, motorista, soropositivo para HIV há oito anos, sem acompanhamento, com quadro de tosse produtiva com secrecão acinzentada e episódios intermitentes de dispnéia há 15 dias. Informava dois episódios pregressos de tuberculose pulmonar (1983 e 2001) tratados. A radiografia de tórax evidenciou áreas de hipotransparência nodular e broncogramas aéreos bilateralmente. A tomografia computadorizada de tórax evidenciou vários achados inespecíficos, dentre eles áreas esparsas de consolidacão, cavitacão, bronquiectasia, opacidade em vidro fosco, espessamento intersticial e broncogramas aéreos. A lavagem broncoalveolar evidenciou numerosas hifas com raros septos bifurcados sugestivos de Aspergillus sp. e a cultura foi positiva para Nocardia sp. e Mycobacterium tuberculosis. Foi instituída terapia com anfotericina B, sulfametoxazol-trimetoprim e anti-retrovirais. Após 20 dias, recebeu alta sem queixas pulmonares. Decorridos 15 dias, retornou com diarréia, febre, disfagia e emagrecimento importante. Foi a óbito após cinco dias, por sepse estafilocócica.