RESUMO
PURPOSE: Dalbavancin is an attractive antibiotic for the treatment of Gram-positive musculoskeletal infections given its long half-life and prolonged duration in cortical bones. For certain patient populations compliance with antibiotic regimens can be problematic. Therefore, the purpose of this study was to assess the effectiveness, tolerance, and compliance of treating prosthetic joint and spinal hardware infections with a unique two-dose regimen of dalbavancin. METHODS: Identification of patients that had prosthetic joint infections and spinal hardware infections from January 1, 2017, through December 31, 2021, that had received a two-dose regimen of dalbavancin for these infections was conducted. Patient demographics, infection recurrence, compliance and adverse drug reactions to the two-dose regimen of dalbavancin were recorded. Furthermore, preserved clinical isolates from these infections were assessed for susceptibility to dalbavancin with microbroth dilutions. RESULTS: All patients were fully compliant with the two dose dalbavancin regimen and no patient had any adverse reactions to the two-dose dalbavancin regimen. Thirteen of fifteen patients (85.7%) have not had any recurrence of their infections and all preserved clinical isolates showed susceptibility to dalbavancin. DISCUSSION: The two-dose regimen of dalbavancin is an effective and attractive option in treating prosthetic joint and spinal hardware infections to forgo long term central venous access and ensure compliance. However, the use of rifampin and suppression antibiotics still needs to be considered when treating these infections. Nonetheless this study supports that a two-dose dalbavancin regimen is a viable alternative in certain clinical settings and consideration for a randomized controlled clinical trial should be entertained to prove its non-inferiority to conventional treatments.
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Antibacterianos , Teicoplanina , Teicoplanina/análogos & derivados , Humanos , Teicoplanina/efeitos adversos , Antibacterianos/efeitos adversos , Osso e Ossos , RifampinaRESUMO
BACKGROUND & AIMS: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub-Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection. METHODS: In this partially randomized, open-label multicentre study conducted in France (NCT03111108; Protocol MK5172-096), treatment-naive participants with GT4 infection and F0-F2 fibrosis were randomized 2:1 to elbasvir (50 mg)/grazoprevir (100 mg) for 8 or 12 weeks. Treatment-naive participants with F3-F4 fibrosis and all treatment-experienced participants (F0-F4) were assigned to elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy. RESULTS: One hundred and seventeen participants were enrolled. Among treatment-naive participants with F0-F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12-week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance-associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug-related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event. CONCLUSION: These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment-experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment-naive individuals with mild fibrosis can be treated effectively with an 8-week regimen.
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Hepacivirus , Hepatite C Crônica , Amidas/uso terapêutico , Antivirais/efeitos adversos , Benzofuranos , Carbamatos/uso terapêutico , Ciclopropanos/uso terapêutico , Quimioterapia Combinada , Egito , França , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Imidazóis , Quinoxalinas/efeitos adversos , Sulfonamidas/uso terapêuticoRESUMO
BACKGROUND AND AIM: Estimates suggest that in Asia, more than 31 million individuals have hepatitis C virus infection. The present analysis was conducted to assess the efficacy and safety of elbasvir/grazoprevir in Asian participants enrolled in the elbasvir/grazoprevir phase 2/3 clinical trials. METHODS: This is an integrated analysis of data from 12 international phase 2/3 clinical trials. Asian participants with chronic hepatitis C virus genotype 1 or 4 infection who received elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks or elbasvir/grazoprevir plus ribavirin for 16 weeks were included in this analysis. The primary end point was sustained virologic response at 12 weeks after completion of therapy (SVR12). RESULTS: Seven hundred eighty Asian participants from 15 countries were included in this analysis. SVR12 was achieved by 756/780 (96.9%) of all participants, including 748/772 (96.9%) of those who received elbasvir/grazoprevir for 12 weeks and 8/8 (100%) of those who received elbasvir/grazoprevir plus ribavirin for 16 weeks. In the genotype 1b-infected population, the SVR12 rate was 691/709 (97.5%), and there was no impact of age, high baseline viral load, or presence of cirrhosis. The most frequently reported adverse events were nasopharyngitis (8.0%), upper respiratory tract infection (5.4%), and diarrhea (5.2%). Twenty participants receiving elbasvir/grazoprevir for 12 weeks reported a total of 25 serious adverse events, and 7 (0.9%) discontinued treatment because of an adverse event. CONCLUSION: Elbasvir/grazoprevir administered for 12 weeks is an effective and generally well-tolerated treatment option for Asian individuals with hepatitis C virus genotype 1b infection.
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Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Idoso , Antivirais/efeitos adversos , Ásia/epidemiologia , Benzofuranos/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Combinação de Medicamentos , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND AND AIM: Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS: C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS: A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.
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Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Adulto , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Aspartato Aminotransferases/sangue , Austrália , Benzofuranos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Farmacorresistência Viral/genética , Ásia Oriental , Feminino , Genótipo , Hepacivirus/enzimologia , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Federação Russa , Resposta Viral Sustentada , Tailândia , Vietnã , Proteínas não Estruturais Virais/metabolismo , Adulto JovemRESUMO
OBJECTIVES: Although direct-acting antiviral regimens have dramatically improved the treatment of hepatitis C virus (HCV) infection, there is some evidence that black race may be an independent predictor of treatment failure. We report a retrospective analysis of black participants receiving elbasvir/grazoprevir (EBR/GZR) in nine phase 2/3 clinical trials. METHODS: Black participants with chronic HCV genotype 1 or 4 (GT1 or GT4) infection who received EBR 50 mg/GZR 100 mg once daily for 12 weeks, or in combination with ribavirin for 16 weeks, were included. The primary end point was sustained virologic response 12 weeks after completion of therapy (SVR12, HCV RNA < 15 IU/mL). RESULTS: Compared with nonblack participants (n = 1310), black participants (n = 332) were more likely to have chronic kidney disease stage 4/5 (9.2% vs. 31.0%, respectively), while other comorbidities were similar between the groups. In black and nonblack participants receiving EBR/GZR for 12 weeks, SVR12 rates were 93.7% (282/301) and 94.2% (1072/1138) in those with GT1 infection, and 93.8% (15/16) and 94.6% (88/93) in those with GT4 infection. SVR12 was 100.0% (15/15) in black participants and 97.5% (77/79) in nonblack participants with GT1 infection receiving EBR/GZR plus ribavirin for 16 weeks. Rates of drug-related adverse events (AEs) were 30% vs. 36.6%, and serious AEs were 7.6% vs. 3.4% in black and nonblack participants, respectively. CONCLUSION: EBR/GZR showed high efficacy in black participants with HCV GT1 or GT4 infection and was generally well tolerated, with a safety profile similar to that reported overall in phase 2/3 clinical trials.
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Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Negro ou Afro-Americano/estatística & dados numéricos , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/isolamento & purificação , Estudos Retrospectivos , Resposta Viral Sustentada , Falha de Tratamento , Adulto JovemRESUMO
Direct-acting antiviral agents have not been studied exclusively in patients with inherited blood disorders and hepatitis C virus (HCV) infection. The objective of the randomized, placebo-controlled, phase III C-EDGE IBLD study was to assess the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) in patients with inherited bleeding disorders and HCV infection. One hundred fifty-nine adults with HCV infection and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled at 31 study sites in the United States, Europe, Australia, Canada, Israel, and Thailand. Patients were given an oral, once-daily, fixed-dose combination of EBR/GZR 50 mg/100 mg for 12 weeks and randomized to the immediate-treatment group (ITG) or deferred-treatment group (DTG; placebo followed by active treatment). The primary endpoints were the proportion of patients in the ITG with unquantifiable HCV RNA 12 weeks posttreatment (sustained virological response 12 weeks after completion of study treatment; SVR12) and the comparison of safety in the ITG and DTG. In the ITG, 100 of 107 patients (93.5%) achieved SVR12, 6 relapsed, and 1 was lost to follow-up. SVR12 was achieved in 94.7% (18 of 19), 97.6% (40 of 41), and 89.4% (42 of 47) of patients with sickle cell disease, ß-thalassemia, and hemophilia A/B or von Willebrand disease, respectively. Serious adverse events were reported by 2.8% (n = 3) and 11.5% (n = 6) of patients in the ITG and DTG, respectively. Hemoglobin levels and international normalized ratio values were similar in patients receiving EBR/GZR and placebo; among patients with hemoglobinopathies, change in mean hemoglobin levels was similar in those receiving EBR/GZR compared to those receiving placebo. CONCLUSION: These results add to the expanding pool of data available for EBR/GZR, indicating a high level of efficacy and favorable tolerability in patients with HCV infection. (Hepatology 2017;66:736-745).
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Benzofuranos/administração & dosagem , Transtornos Herdados da Coagulação Sanguínea/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Quinoxalinas/administração & dosagem , Administração Oral , Adulto , Amidas , Biópsia por Agulha , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Transtornos Herdados da Coagulação Sanguínea/tratamento farmacológico , Carbamatos , Ciclopropanos , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/diagnóstico , Humanos , Imuno-Histoquímica , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Valores de Referência , Índice de Gravidade de Doença , Sulfonamidas , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: The aim of this integrated analysis was to assess the efficacy of the once-daily combination of elbasvir 50 mg and grazoprevir 100 mg, with and without ribavirin in HCV genotype 4 (GT4)-infected participants enrolled in the Phase 2/3 clinical programme with elbasvir/grazoprevir. METHODS: Treatment-naïve and treatment-experienced participants 18 years of age or older with chronic HCV GT4 infection and baseline HCV RNA ≥10 000 IU/mL were included in the analysis. The analysis population was the full analysis set (FAS; all participants who received at least 1 dose of study medication) and a total of 155 HCV GT4 participants were evaluated. The primary endpoint was sustained virologic response at week 12 (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the completion of study therapy). RESULTS: Overall, among GT4-infected participants treated with 12 or 16 weeks of elbasvir/grazoprevir ± ribavirin, the SVR12 efficacy rates were 96.4% (107/111) in treatment-naïve participants and 88.6% (39/44) in treatment-experienced participants. The SVR12 rates were 96.0% (97/101) in treatment-naïve participants treated with 12 weeks of elbasvir/grazoprevir and 100% (8/8) in treatment-experienced participants treated with 16 weeks of elbasvir/grazoprevir plus ribavirin. Efficacy was not impacted by GT4 subtype. CONCLUSIONS: The regimens of 12 weeks of elbasvir/grazoprevir without ribavirin, and 16 weeks of elbasvir/grazoprevir plus ribavirin, were efficacious in HCV GT4-infected treatment-naïve and treatment-experienced participants respectively. Baseline NS5A resistance-associated substitutions did not impact the efficacy of elbasvir/grazoprevir in GT4-infected participants.
Assuntos
Antivirais/administração & dosagem , Benzofuranos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Quinoxalinas/administração & dosagem , Adulto , Idoso , Amidas , Carbamatos , Ciclopropanos , Farmacorresistência Viral , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Humanos , Internacionalidade , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Sulfonamidas , Resposta Viral Sustentada , Adulto JovemRESUMO
BACKGROUND: Direct-acting antiviral drugs have a high cure rate and favourable tolerability for patients with hepatitis C virus (HCV). Shorter courses could improve affordability and adherence. Sofosbuvir and ledipasvir with ribavirin have high efficacy when taken for 8 weeks but not for 6 weeks. We assessed whether the addition of a third direct-acting antiviral drug to sofosbuvir and ledipasvir would allow a shorter treatment duration. METHODS: In this single-centre, open-label, phase 2A trial, we sequentially enrolled treatment-naive patients with HCV genotype 1 infection into three treatment groups: 12 weeks of sofosbuvir and ledipasvir; 6 weeks of sofosbuvir, ledipasvir, and GS-9669; or 6 weeks of sofosbuvir, ledipasvir, and GS-9451. Patients and investigators were not masked to treatment assignment. The primary endpoint was the propotion of patients with sustained viral response at 12 weeks after treatment completion (SVR12), assessed by serum HCV RNA concentrations lower than 43 IU/mL (the lower limit of quantification). We did an intention-to-treat analysis for the primary endpoint and adverse events. This study is registered with ClinicalTrials.gov, number NCT01805882. FINDINGS: Between Jan 11, 2013, and Dec 17, 2013, we enrolled 60 patients, and sequentially assigned them into three groups of 20. We noted an SVR12 in all 20 patients (100%, 95% CI 83-100) allocated to sofosbuvir and ledipasvir for 12 weeks; in 19 (95%, 75-100) of the 20 patients allocated to sofosbuvir, ledipasvir, and GS-9669 for 6 weeks (one patient relapsed 2 weeks after completion of treatment); and in 19 (95%, 75-100%) of the 20 patients allocated to sofosbuvir, ledipasvir, and GS-9451 for 6 weeks (one patient was lost to follow-up after reaching sustained viral response at 4 weeks). Most adverse events were mild and no patients discontinued treatment. Two serious adverse events occurred (pain after a post-treatment liver biopsy and vertigo), both unrelated to study drugs. INTERPRETATION: In this small proof-of-concept study, two different three-drug regimens that were given for 6 weeks resulted in high cure rates for HCV infection with excellent tolerability. Addition of a third potent direct-acting antiviral drug can reduce the duration of treatment required to achieve sustained viral response in patients with chronic HCV genotype 1 infection without cirrhosis. FUNDING: National Institute of Allergy and Infectious Diseases (NIAID), National Cancer Institute and Clinical Center Intramural Program, German Research Foundation, National Institutes of Health, Gilead Sciences.
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Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Furanos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Quinolinas/uso terapêutico , RNA Viral/sangue , Ribavirina/uso terapêutico , Tiofenos/uso terapêutico , Uridina Monofosfato/análogos & derivados , Idoso , Estudos de Coortes , Quimioterapia Combinada/métodos , Feminino , Hepacivirus/genética , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Sofosbuvir , Resultado do Tratamento , Uridina Monofosfato/uso terapêutico , Carga ViralRESUMO
IMPORTANCE: There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV). OBJECTIVE: To evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed. INTERVENTIONS: Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment. RESULTS: Forty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug. CONCLUSIONS AND RELEVANCE: In this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01878799.
Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Administração Oral , Adulto , Benzimidazóis/efeitos adversos , Coinfecção , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/induzido quimicamente , RNA Viral , Sofosbuvir , Resultado do Tratamento , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/uso terapêutico , Carga ViralRESUMO
Chronic hepatitis B and C are the leading causes of liver disease and liver transplantation worldwide. Ability to mount an effective immune response against both HBV and HCV is associated with spontaneous clearance of both infections, while an inability to do so leads to chronicity of both infections. To mount an effective immune response, both innate and adaptive immune responses must work in tandem. Hence, developing protective immunity to hepatitis viruses is an important goal in order to reduce the global burden of these two infections and prevent development of long-term complications. In this regard, the initial interactions between the pathogen and immune system are pivotal in determining the effectiveness of immune response and subsequent elimination of pathogens. Toll-like receptors (TLRs) are important regulators of innate and adaptive immune responses to various pathogens and are often involved in initiating and augmenting effective antiviral immunity. Immune-based therapeutic strategies that specifically induce type I interferon responses are associated with functional cure for both chronic HBV and HCV infections. Precisely, TLR7 stimulation mediates an endogenous type I interferon response, which is critical in development of a broad, effective and protective immunity against hepatitis viruses. This review focuses on anti-viral strategies that involve targeting TLR7 that may lead to development of protective immunity and eradication of hepatitis B.
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Antivirais/farmacologia , Hepatite B/tratamento farmacológico , Hepatite C/tratamento farmacológico , Receptor 7 Toll-Like/efeitos dos fármacos , Antivirais/uso terapêutico , HumanosRESUMO
IMPORTANCE: The efficacy of directly acting antiviral agents in interferon-free regimens for the treatment of chronic hepatitis C infections needs to be evaluated in different populations. OBJECTIVE: To determine the efficacy and safety of sofosbuvir with weight-based or low-dose ribavirin among a population with unfavorable treatment characteristics. DESIGN, SETTING, AND PATIENTS: Single-center, randomized, 2-part, open-label phase 2 study involving 60 treatment-naive patients with hepatitis C virus (HCV) genotype 1 enrolled at the National Institutes of Health (October 2011-April 2012). INTERVENTIONS: In the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study end point was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR24]). RESULTS: In the first part of the study, 9 participants (90%; 95% CI, 55%-100%) achieved SVR24. In the second part, 7 participants (28%) in the weight-based group and 10 (40%) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68% (95% CI, 46%-85%) in the weight-based group and 48% (95% CI, 28%-69%; P = .20) in the low-dose group. Twenty individuals participated in a pharmacokinetic-viral kinetic substudy, which demonstrated a slower loss rate of infectious virus in relapsers than in participants who achieved SVR (clearance, 3.57/d vs 5.60/d; P = .009). The most frequent adverse events were headache, anemia, fatigue, and nausea. There were 7 grade 3 events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. No one discontinued treatment due to adverse events. CONCLUSION AND RELEVANCE: In a population of patients with a high prevalence of unfavorable traditional predictors of treatment response, a 24-week regimen of sofosbuvir and weight-based or low-dose ribavirin resulted in SVR24 rates of 68% and 48%, respectively. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01441180.
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Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Ribavirina/administração & dosagem , Uridina Monofosfato/análogos & derivados , Antivirais/efeitos adversos , Antivirais/farmacocinética , Peso Corporal , Feminino , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Hepatite C/genética , Humanos , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Ribavirina/efeitos adversos , Ribavirina/farmacocinética , Sofosbuvir , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/farmacocinética , Carga ViralRESUMO
A 36-year-old male with headaches was empirically treated for herpes simplex virus meningitis; CSF PCR testing later confirmed varicella zoster virus meningitis. Valacyclovir was increased to 2 g QID for remaining duration of therapy with full recovery. This case highlights the importance of comprehensive testing and proper treatment adjustment for rarer etiologies of aseptic meningitis.
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Africa carries a disproportionate burden of the global HIV endemic, accounting for two thirds of the global 33.3 million people living with HIV. While tremendous advances have been made in addressing the HIV epidemic in Africa, considerable challenges remain. Testing for HIV increased by 86% from 2007 to 2009 but more than 75% of people 15-49 years remain unaware of their HIV status. CD4 count at diagnosis tends to be low and linkage to care and treatment is suboptimal. The scale-up of antiretroviral therapy is ongoing but is hampered by the lack of diagnostic capability to monitor response to therapy and a substantial healthcare workforce shortage. Prevention strategies such as male circumcision, pre-exposure prophylaxis, and antiretroviral therapy for prevention have generated great excitement but cost and healthcare infrastructure deficiencies may limit their widespread applicability. Operational research to validate and inform treatment decisions, health care policies, and prevention strategies is sorely needed.
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Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne illness in the United States. Transmission occurs primarily through the bite of an infected deer tick (Ixodes scapularis). Identification of an erythema migrans rash following a tick bite is the only clinical manifestation sufficient to make the diagnosis of Lyme disease in the absence of laboratory confirmation. The Centers for Disease Control and Prevention recommends a two-tier serologic testing protocol using an enzyme-linked immunosorbent assay initially, followed by the more specific Western blot to confirm the diagnosis when the assay samples are positive or equivocal. The treatment of Lyme disease is determined mainly by the clinical manifestations of the disease. Doxycycline is often the preferred agent for oral treatment because of its activity against other tick-borne illnesses. Preventive measures include avoiding areas with high tick burdens, wearing protective clothing, using tick repellants (e.g., diethyltoluamide [DEET]), performing frequent body checks and bathing following outdoor activities, and instituting environmental landscape modifications (e.g., grass mowing, deer exclusion fencing) to reduce the tick burden. Although there is controversy regarding treatment of post-Lyme disease syndrome and chronic Lyme disease, there is no biologic or clinical trial evidence indicating that prolonged antibiotic therapy is of benefit.
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Doença de Lyme/diagnóstico , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Vetores Aracnídeos/microbiologia , Progressão da Doença , Humanos , Ixodes/microbiologia , Doença de Lyme/tratamento farmacológico , Doença de Lyme/patologia , Doença de Lyme/transmissão , Pele/patologiaRESUMO
OBJECTIVES: Primary Objective: To evaluate the efficacy and safety of oral administration of imatinib combined with the Best Conventional Care (BCC) versus placebo plus BCC in hospitalized patients with COVID-19. HYPOTHESIS: Addition of imatinib to the BCC will provide a superior clinical outcome for patients with COVID-19 compared with BCC plus placebo. This hypothesis is on the basis of 1) intralysosomal entrapment of imatinib will increase endosomal pH and effectively decrease SARS-CoV-2/cell fusion, 2) kinase inhibitory activity of imatinib will interfere with budding/release or replication of SARS-CoV-2, and 3) because of the critical role of mechanical ventilation in the care of patients with ARDS, imatinib will have a significant clinical impact for patients with critical COVID-19 infection in Intensive Care Unit (ICU). TRIAL DESIGN: This is an individual patient-level randomized, double-blind, placebo-controlled, two-parallel arm phase 3 study to evaluate the safety and efficacy of imatinib for the treatment of hospitalized adults with COVID-19. Participants will be followed for up to 60 days from the start of study drug administration. This trial will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. PARTICIPANTS: Inclusion Criteria: Patients may be included in the study only if they meet all of the following criteria: 1) Ability to understand and willingness to sign a written informed consent document. Informed consent must be obtained prior to participation in the study. For patients who are too unwell to provide consent such as patients on invasive ventilator or extracorporeal membrane oxygenation (ECMO), their Legally Authorized Representative (LAR) can sign the informed consent, 2) Hospitalized patients ≥18 years of age, 3) Positive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 in the respiratory tract sample (oropharyngeal, nasopharyngeal or bronchoalveolar lavage (BAL)) by Center for Disease Control or local laboratory within 7 days of randomization, 4) Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study. EXCLUSION CRITERIA: Patients meeting any of the following criteria are not eligible for the study: 1) Patients receiving any other investigational agents in a clinical trial. Off-label use of agents such as hydroxychloroquine is not an exclusion criterion, 2) Pregnant or breastfeeding women, 3) Patients with significant liver or renal dysfunction at the time of screening as defined as: 3.1) Direct bilirubin >2.5 mg/dL, 3.2) AST, ALT, or alkaline phosphatase >5x upper limit of normal, 3.3) eGFR ≤30 mL/min or requiring renal replacement therapy, 4) Patients with significant hematologic disorder at screen as defined as: 4.1) Absolute neutrophil count (ANC) <500/µL, 4.2) Platelet <20,000/µL, 4.3) Hemoglobin <7 g/dL, 5) Uncontrolled underlying illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements, 6) Known allergy to imatinib or its component products, 7) Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study. Both men and women of all races and ethnic groups are eligible for this trial. University of Maryland Medical Center, Baltimore, MD is the initiating site. The study may be opened in other centers on the basis of the accrual rate or the magnitude of the COVID-19 pandemic. INTERVENTION AND COMPARATOR: Imatinib: All doses of imatinib should be administered with a meal and a large glass of water. Imatinib can be dissolved in water or apple juice for patients having difficulty swallowing. In this study, patients with confirmed positive COVID-19 tests receive imatinib for a total of 14 days; 400 mg orally daily Days 1-14. Imatinib 400 mg tablets will be encapsulated using size 000 capsules and cellulose microcrystalline filler. For patients on ventilator or ECMO, imatinib will be given as oral suspension (40 mg/mL). To make the oral suspension, imatinib tablets will be crushed and mixed in Ora-sweet solution to yield a concentration of 40 mg/mL suspension by pharmacy. Additionally, in the absence of supportive microbiological testing results, we confirm that the in-use stability period for the prepared imatinib suspensions will be 24 hours at room temperature or 7 days at refrigerated conditions. The pharmacy staff will follow the American Society Health-System Pharmacists (ASHP) guidelines for handling hazardous drugs. Placebo: The matching placebo will be packaged by Investigational Drug Service Pharmacy at University of Maryland Medical Center. The placebos will be prepared using size 000 capsules and cellulose microcrystalline filler. Imatinib 400 mg capsules and placebo capsules will be identical form and color. For patients on ventilator or ECMO, placebo will be given as oral suspension with similar process for making imatinib suspension. Concomitant Medications/supportive care: In both arms, patients can receive concomitant available local standard of care antipyretics, antibacterials, antivirals, antifungals and anti-inflammatory including hydroxychloroquine at the discretion of the treating physician as necessary. For other drug-drug interactions particularly with CYP P450, the treating physician should consider the risk and benefit of drug administration based on available information. Co-administration of off-label immunomodulatory treatments for COVID-19 including but not limited to corticosteroids, sarilumab, clazakizumab, tocilizumab, and anakinra will be allowed but may affect interpretability of study outcomes. The timing, dosing, and duration of these treatments will be meticulously collected, including any of these treatments that may be used for participants who experience progression of COVID-19 disease after study enrollment. Two analyses will be performed, the primary analysis will compare the primary endpoint in the two trial arms irrespective of any other treatment; the second analysis will be stratified for co-administration of immunomodulatory drugs. MAIN OUTCOMES: The primary endpoint is the proportion of patients with a two-point improvement at Day 14 from baseline using the 8-category ordinal scale. The ordinal scale is an evaluation of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. The secondary endpoints include: All-cause mortality at Day 28, All-cause mortality at Day 60, Time to a 2-point clinical improvement difference over baseline, Duration of hospitalization, Duration of ECMO or invasive mechanical ventilation (for subjects who are on ECMO or mechanical ventilation at Day 1), Duration of ICU stay (for subjects who are in ICU at Day 1), Time to SARS-CoV-2 negative by RT-PCR, Proportion of patients with negative oropharyngeal or nasopharyngeal swab for SARS-CoV-2 by RT-PCR on days 5, 10, 14, 21, and 28 after starting treatment, Proportion of subjects with serious adverse events, Proportion of subjects who discontinue study drug due to adverse events. The exploratory endpoints include: Determine the impact of treatment arms on IL-6 levels, Obtain blood/peripheral blood mononuclear cells (PBMCs) for storage to look at transcriptomics in severe disease, Association of major histocompatibility complex (MHC) with severity of illness, Mean change in the ordinal scale from baseline, Time to an improvement of one category from admission using an ordinal scale, Duration of hospitalization, Duration of new oxygen use, Number of oxygenation free days, Duration of new mechanical ventilation, Number of ventilator free days. RANDOMIZATION: Eligible patients will be uniformly randomized in 1:1 ratio to receive either imatinib or placebo for 14 days. Both groups will receive the BCC. The randomized treatment allocations use stratified, permuted block randomization with a variable block size; blocks are generated using a validated random number generator. In order to balance the severity of the respiratory illness between the two arms, randomization will be stratified based on radiographic findings and oxygen requirements: 1) Severe disease: evidence of pneumonia on chest X-ray or CT scan OR chest auscultation (rales, crackles), and SpO2 ≤92% on ambient air or PaO2/FiO2 <300 mmHg, and requires supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device; 2) Critical disease: requires supplemental oxygen delivered by non-rebreather mask or high flow cannula OR use of invasive or non-invasive ventilation OR requiring treatment in an intensive care unit, use of vasopressors, extracorporeal life support, or renal replacement therapy. BLINDING (MASKING): The participants, caregivers, and the statistician are blinded to group assignment. The only people who are not blinded are Site Pharmacists. Blinding will be performed via a specific randomization process. Centralized, concealed randomization will be executed by the Primary Site's Pharmacist. Data on eligible consented cases will be submittedelectronically on the appropriate on-study form to the pharmacy, where the patient is randomized to imatinib or placebo. Imatinib 400 mg capsules and placebo capsules will be identical form and color. For patients on ventilator or ECMO, placebo will be given as oral suspension with similar process for making imatinib suspension. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The trial is designed as a double-blind, two-parallel arm, randomized controlled trial with a uniform (1:1) allocation ratio to: Arm A) Imatinib or Arm B) Placebo. Patients in both arms will receive the BCC per local institutional standards at the discretion of the treating physician. Group sample sizes of 102 in Arm A and 102 in Arm B achieve 80.6% power to detect a difference between the group proportions of 0.20. The proportion in Arm A (imatinib treatment arm) is assumed to be 0.30 under the null hypothesis and 0.50 under the alternative hypothesis. The proportion in Arm B (placebo control arm) is 0.30. The test statistic used is the two-sided Fisher's Exact Test. The significance level of the test is targeted at 0.05. The significance level actually achieved by this design is α=0.0385. The power of the test is calculated using binomial enumeration of all possible outcomes. The primary analysis will be conducted using an intention to treat principle (ITT) for participants who at least receive one dose of study drug or placebo. The sample size is not inflated for dropouts. All patients will be evaluable irrespective of the clinical course of their disease. TRIAL STATUS: Current protocol version is 1.2 from May 8, 2020. The recruitment started on June 15, 2020 and is ongoing. We originally anticipated that the trial would finish recruitment by mid 2021. We are aware of the enrollment requirement of approximately 200 patients, which is required to provide scientific integrity of the results. We are also aware of the fact that enrolling this number of patients in a single-site at University of Maryland Medical Center (UMMC) may take longer than expected, particularly taken into account other competing studies. For this reason, we are actively considering opening the protocol in other sites. After identification of other sites, we will fulfill all regulatory requirements before opening the protocol in other sites. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04394416 . First Posted: May 19, 2020; Last Update Posted: June 4, 2020. FDA has issued the "Study May Proceed" Letter for this clinical trial under the Investigational New Drug (IND) number 149239. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Mesilato de Imatinib , Pandemias , Pneumonia Viral , Administração Oral , Adulto , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Cuidados Críticos/métodos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Monitoramento de Medicamentos , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do TratamentoRESUMO
Background: In the United States, the number of new cases of hepatitis C virus infection has risen in recent years, driven largely by transmission among young white adults in their 20s and 30s. Herein, we report an integrated analysis of participants with hepatitis C virus infection aged ≤35 years from 12 phase II/III clinical trials of elbasvir/grazoprevir.Methods: Treatment-naive and -experienced adults with hepatitis C virus genotype 1 or 4 infection received elbasvir (50 mg/day)/grazoprevir (100 mg/day) for 12 weeks without ribavirin. Analyses were stratified according to participant age (≤35 years vs >35 years). The primary endpoint was sustained virologic response (hepatitis C virus RNA < lower limit of quantitation at 12 weeks after completion of therapy).Results: Sustained virologic response was achieved by 98.9% (271/274) of participants aged ≤35 years and by 96.9% (2093/2160) aged >35 years. Three participants aged ≤35 years with genotype 1b infection relapsed. Eight participants with genotype 1a infection and baseline non-structural protein 5 A resistance-associated substitutions achieved sustained virologic response. Similarly, all 85 participants aged ≤35 years with genotype 1a infection and no baseline non-structural protein 5 A resistance-associated substitutions achieved sustained virologic response. Safety was favorable, with the incidence of drug-related adverse events similar in younger and older participants (30.1% vs 30.6%). One participant (0.4%) aged ≤35 years and 15 participants (0.7%) aged >35 years discontinued treatment owing to adverse events.Conclusions: Elbasvir/grazoprevir for 12 weeks was safe and highly effective in participants aged ≤35 years with hepatitis C virus genotype 1 or 4 infection.
Assuntos
Amidas/administração & dosagem , Antivirais/administração & dosagem , Benzofuranos/administração & dosagem , Carbamatos/administração & dosagem , Ciclopropanos/administração & dosagem , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Quinoxalinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas/efeitos adversos , Benzofuranos/efeitos adversos , Carbamatos/efeitos adversos , Ciclopropanos/efeitos adversos , Feminino , Hepacivirus/genética , Hepatite C/virologia , Humanos , Imidazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Adulto JovemRESUMO
PURPOSE: Hepatitis C virus (HCV) infection is a major healthcare concern in Russia, where almost 5 million individuals are viremic. Elbasvir/grazoprevir is a fixed-dose combination therapy for the treatment of HCV genotype 1 and genotype 4 infection. The present analysis aimed to assess the safety and efficacy of elbasvir/grazoprevir in individuals with HCV infection enrolled at Russian study sites in the C-CORAL study. PATIENTS AND METHODS: C-CORAL (Protocol PN-5172-067; NCT02251990) was a Phase 3, placebo-controlled, double-blind study conducted throughout Asia and Russia. Treatment-naive participants with chronic HCV infection were randomly assigned to receive immediate or deferred treatment with elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks. Participants in the immediate-treatment group received elbasvir/grazoprevir for 12 weeks, and those in the deferred-treatment group received placebo for 12 weeks, followed by open-label elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12). RESULTS: One hundred and nineteen Russian participants were randomized (immediate-treatment group, n=88; deferred-treatment group, n=31). Most participants were white (99%) with HCV genotype 1b infection (97%) and mild-to-moderate (F0-F2) fibrosis (70%). SVR12 was achieved by 98.9% participants in the immediate-treatment group and by 100% of those receiving deferred elbasvir/grazoprevir in the deferred-treatment group. One participant relapsed with nonstructural protein 5A (NS5A) L28M and Y93H resistance-associated substitutions at baseline and at time of failure. Drug-related adverse events were reported by 19% of participants receiving elbasvir/grazoprevir in the immediate-treatment group and by 16% of those receiving placebo in the deferred-treatment group. No serious adverse event or deaths occurred, and no participant discontinued treatment owing to an adverse event. CONCLUSION: Elbasvir/grazoprevir for 12 weeks was highly effective in treatment-naive Russian individuals with HCV genotype 1b infection.
RESUMO
BACKGROUND AND AIM: In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China. METHODS: Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate-treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred-treatment group, DTG). The primary efficacy end-point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end-point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN-5172-067). RESULTS: A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug-related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug-related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient-reported outcomes indicate improved quality of life at follow-up week 4 in participants receiving EBR/GZR compared to placebo. CONCLUSION: EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection.
RESUMO
PURPOSE: The once-daily nucleoside reverse transcriptase inhibitor backbone of tenofovir and emtricitabine has been proven effective in combination with efavirenz and protease inhibitors in large clinical trials. This study evaluated tenofovir and emtricitabine in combination with nevirapine. METHODS: Viral load was assessed at baseline, Day 3, and Day 7 in addition to Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84 in 10 antiretroviral-naïve patients participating in an open-label clinical trial of tenofovir and emtricitabine once daily in combination with nevirapine twice daily. RESULTS: All patients achieved viral decay with this combination. Two patients discontinued prior to virologic suppression, one with a viral load of 55 copies/mL. Virologic suppression (<50 copies/mL) was achieved by Week 24 in the remaining 8 patients. An undetectable viral load was maintained during > or =60 weeks follow-up. CONCLUSION: In this study of treatment-naïve patients, the combination of tenofovir and emtricitabine plus twice-daily nevirapine produced sustained viral load decay in patients including those with a high baseline viral load.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/administração & dosagem , Desoxicitidina/análogos & derivados , Infecções por HIV/tratamento farmacológico , Nevirapina/administração & dosagem , Organofosfonatos/administração & dosagem , Carga Viral/efeitos dos fármacos , Adenina/administração & dosagem , Alcinos , Benzoxazinas/uso terapêutico , Ciclopropanos , Desoxicitidina/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Emtricitabina , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Estudos Prospectivos , Tenofovir , Fatores de TempoRESUMO
Non-typhoidal salmonella (NTS) bacteremia is a significant cause of morbidity and mortality in HIV-infected individuals worldwide. Recent reports have noted increasing resistance of NTS isolates to fluoroquinolones, the recommended first-line therapy for NTS bacteremia. The outcomes and risk factors for NTS bacteremia in HIV-infected patients in an urban US setting were evaluated. From January 2002 to December 2006, 26 episodes of NTS bacteremia were identified in 16 patients. The risk factors for NTS bacteremia were low CD4 count, high viral load, and lack of antiretroviral therapy (ART). Recurrences appeared related to lack of immune reconstitution in patients not on ART. Unlike reports from Asia, no fluoroquinolone resistance was identified in any of the Salmonella strains isolated in this setting. Optimal treatment of NTS in the HIV-infected patient in the United States should include therapy with fluoroquinolones as well as attaining complete viral suppression and immune reconstitution with ART.