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1.
Expert Opin Pharmacother ; 21(3): 261-273, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31914336

RESUMO

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar.


Assuntos
Benzazepinas/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Indóis/administração & dosagem , Isoquinolinas/administração & dosagem , Sulfonamidas/administração & dosagem , Antivirais/uso terapêutico , Combinação de Medicamentos , Genótipo , Hepacivirus/efeitos dos fármacos , Humanos , Cirrose Hepática/prevenção & controle , Resposta Viral Sustentada , Comprimidos , Resultado do Tratamento
2.
Sr Care Pharm ; 35(1): 13-28, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883541

RESUMO

OBJECTIVE: To provide a review of the epidemiology, clinical presentation, screening, diagnosis, treatment, and prevention of hepatitis C with an emphasis on older adults. DATA SOURCES: PubMed and Google Scholar were searched for relevant literature using a combination of the following terms: hepatitis C, epidemiology, hepatitis C virus (HCV), diagnosis, treatment, direct-acting antivirals (DAAs), and older adults. In addition, websites of the hepatitis C guidelines, Centers for Disease Control and Prevention (CDC), and manufacturers of DAAs were also reviewed for relevant information. (The authors reviewed the literature through May 2019. STUDY SELECTION/DATA EXTRACTION: The key resources reviewed were the CDC website, American Association for the Study of Liver Diseases/Infectious Diseases Society of America hepatitis C guidelines, prescribing information of DAAs, and pivotal clinical trials of DAAs. DATA SYNTHESIS: Hepatitis C disproportionately affects baby boomers and people who inject drugs (PWID). CDC recommends screening adults born from 1945 to 1965 and high-risk patients for the presence of hepatitis C antibody. The goal of therapy is to achieve sustained virologic response, defined as undetectable HCV ribonucleic acid 12 weeks after treatment completion. Treatment for those who are treatment-naive with or without compensated cirrhosis consists of administration of DAAs orally for 8 to 12 weeks. Regimen selection depends on HCV genotype, presence or absence of cirrhosis, comorbid conditions, and concurrent medications. Currently recommended DAAs are highly effective, well tolerated, and can be associated with significant drug interactions particularly in older adults. Access to DAAs remains an obstacle for many patients. CONCLUSION: Hepatitis C is common among baby boomers and PWID. Screening is recommended in these patient populations. Treatment with DAAs is curative and well tolerated.


Assuntos
Hepatite C , Idoso , Antivirais , Hepacivirus , Humanos , Cirrose Hepática , Resposta Viral Sustentada , Estados Unidos
3.
Arq Gastroenterol ; 56(4): 394-398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800735

RESUMO

BACKGROUND: In recent years the management of hepatitis C virus infection and the possibility of its eradication have been researched due to the importance that they represent in the health of the world population. Obtaining data that help to cope with this pathology improves the quality of life of those affected by it. The present study evaluated the effectiveness of direct-acting antiviral therapies provided by the Brazilian Ministry of Health in accordance to the Clinical Protocol and Therapeutic Guidelines of 2015. OBJECTIVE: To evaluate the epidemiological profile of patients with chronic hepatitis C and the rate of sustained virologic response using direct-acting antivirals of all individuals that attended the referral service for the treatment of chronic hepatitis C at the Hospital of the Federal University of Rio Grande. METHODS: This was an observational, retrospective/prospective study with all patients with chronic hepatitis C who had their treatments available from December 2015 to August 2017 according to the criteria of the Clinical Protocol and Therapeutic Guidelines of 2015. In the first phase, the clinical and demographic variables of all individuals enrolled in a treatment for hepatitis C were selected and collected from the Reference Service database. In the second phase, treatment data were collected. The outcome variable, sustained virologic response, was defined as an undetectable viral load on the blood test three months after the end of treatment. The descriptive and bivariate analyzes were performed with Pearson's chi-square and Fisher's Exact test, adopting a P value ≤0.05 in the SPSS 20 software. RESULTS: Of the 252 participants in the study, 228 (90.5%) had a sustained virologic response, 55.2% were male with an average age of 58.6 years (SD±9.1). Genotype 1 was the most prevalent, observed in 54.4% of the participants, and 87.4% of the patients had moderate/advanced hepatic fibrosis. After the statistical analysis, it was observed that the individuals with genotype 3 and moderate/advanced hepatic fibrosis had lower sustained virologic response rate (P=0.05 and P=0.04, respectively). CONCLUSION: It was observed that the use of direct-acting antivirals, in comparison to previous therapeutic regimens, increases the sustained virologic response, reaching all patients with mild fibrosis. This study provides information that helps in the hepatitis C treatment by showing that prescribing early treatment for patients without hepatic fibrosis and/or genotype 3 virus could increase therapeutic effectiveness.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Resposta Viral Sustentada , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral
5.
Transplant Proc ; 51(9): 2958-2961, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629537

RESUMO

Taking charge of a liver transplanted (LT) patient implies not only to follow up the transplanted organ (eg, immunosuppression and cancer risk) but also to deal with the prevailing patient's active problems. The recurrence of hepatitis C on the graft has historically been one of the main active problems to be addressed, leading to 30% to 40% mortality per se in these patients and has involved many resources in the hepatological centers responsible for the follow-up. We verified how much the availability of the new drugs with direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) has impacted the mortality within the assisted population, changing its characteristics and addressing new clinical issues in the LT-patients. We performed a retrospective comparison between 230 LT patients followed up during pre-DAA era (group 1, with 88 HCV RNA-positive) and 244 patients observed from 2014 onward when DAAs became available (group 2, with 79 HCV RNA-positive). Fifty-two antiviral therapies were performed in group 1 with 18 sustained virologic response (SVR) (35%) and 53 treatments, of which 37 were retreatments, in group 2 with 51 SVR (96%), P = .0001. Deaths for HCV-related causes were 19 of 33 (57%) in group 1 and 7 of 24 (24%) in group 2, P = .01. The Kaplan-Meier showed a dramatic reduction in excess mortality in HCV-LT patients after the availability of DAAs. These results suggest that HCV is no longer the main active problem of follow-up in liver transplants, therefore the resources can be relocated to take care of other clinical aspects.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Transplante de Fígado , Resposta Viral Sustentada , Feminino , Seguimentos , Hepacivirus , Hepatite C Crônica/mortalidade , Humanos , Transplante de Fígado/mortalidade , Masculino , Estudos Retrospectivos
6.
AIDS Rev ; 21(3): 135-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532396

RESUMO

Since HIV has evolved from being a fatal illness to a chronic condition, this brings new challenges relating to long-term health, as increasing numbers of people living with HIV (PLHIV) navigate their lives beyond viral suppression. This review presents the challenges facing patients and health-care providers managing HIV in Europe today. We highlight the challenges that the evolving landscape in HIV brings, including managing an aging and more diverse population of PLHIV; this requires a shift from managing disease to managing health and may best be achieved by multidisciplinary teams in the long term. We introduce the concept of "health goals for me:" an individualized approach to the management of HIV, and use this as the basis for a proposed framework for assessing health-related quality of life for PLHIV. Our framework comprises a continuous cycle of "ask and measure," "feedback and discussion," and "intervention," based on collaboration between the health-care professional and patient. For improved long-term management of PLHIV, we consider that this framework should become an intrinsic part of HIV care in the future and that the "health goals for me" concept be used as a tool to facilitate healthy living for PLHIV beyond viral suppression.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Gerenciamento Clínico , Infecções por HIV/tratamento farmacológico , Qualidade de Vida , Resposta Viral Sustentada , Europa (Continente) , Humanos
7.
Gastroenterology ; 157(6): 1506-1517.e1, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31401140

RESUMO

BACKGROUND & AIMS: Treatment options are limited for patients with hepatitis C (HCV) infection with treatment failure after sofosbuvir plus an NS5A inhibitor. There are some data for the efficacy of glecaprevir/pibrentasvir (G/P) in these patients. We performed a randomized trial of the safety and efficacy of 12 and 16 weeks of G/P, with or without ribavirin, in patients with HCV genotype 1 infection with treatment failure after sofosbuvir and an NS5A inhibitor. METHODS: We performed a phase 3b, open-label study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor. Patients without cirrhosis were randomly assigned to groups that received G/P for 12 weeks (n = 78, group A) or 16 weeks (n = 49, group B). Patients with compensated cirrhosis were randomly assigned to groups that received G/P and ribavirin for 12 weeks (n = 21, group C) or G/P for 16 weeks (n = 29, group D). The primary end point was a sustained virologic response 12 weeks after treatment. Samples collected at baseline and at time of treatment failure were sequenced for resistance-associated substitutions in NS3 and NS5A. RESULTS: Of the 177 patients in the 4 groups, 81% were men, 79% had HCV genotype 1a infection, and 44% were black. Proportions of patients with sustained virologic response 12 weeks after treatment in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. The treatment failed in 13 (7.3%) patients with HCV genotype 1a infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C (6.1%), and 1 (3.4%) in group D. Most patients had baseline resistance-associated substitutions in NS5A. Treatment-emergent resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients with treatment failure, respectively. G/P was well tolerated. Ribavirin increased adverse events but did not increase efficacy. CONCLUSIONS: In a randomized study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor, 16 weeks treatment with G/P produced sustained virologic response 12 weeks after treatment in >90% of patients, including those with compensated cirrhosis. ClinicalTrials.gov, Number: NCT03092375.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/farmacologia , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Combinação de Medicamentos , Farmacorresistência Viral Múltipla/genética , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas/farmacologia , Pirrolidinas/uso terapêutico , Quinoxalinas/farmacologia , Quinoxalinas/uso terapêutico , Ribavirina/farmacologia , Ribavirina/uso terapêutico , Sofosbuvir/farmacologia , Sofosbuvir/uso terapêutico , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Falha de Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética
8.
Acta Med Indones ; 51(2): 128-136, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31383827

RESUMO

BACKGROUND: HIV infection in HCV-infected patients accelerates disease progression and reduces the success rate of Peg-IFN/RBV treatment. HCV mutation in NS5A-ISDR/PKR-BD region improved the outcome in HCV monoinfection treated with Peg-IFN/RBV. SNP-IL28B polymorphism is predicted to have an effect on HCV quasispecies evolution. However, the role of NS5A mutation and SNP IL-28B in HIV-HCV coinfection is still unclear. The aim of the study is to determine the role of HCV NS5A-ISDR/PKR-BD mutation and SNP IL-28 polymorphism on the successfulness of Peg-IFN/RBV therapy in HCV-HIV coinfection. METHODS: prospective cohort was performed in this study. Plasma sample were obtained from 30 and 8 patients with HCV-HIV coinfection and HCV monoinfection, respectively. PCR nucleotide sequencing was performed after RNA virus extraction and cDNA synthesis. Protein secondary structure and prediction of mutation function were analyzed using PredictProtein (PP) program. RESULTS: sixteen HCV-HIV coinfected patients and none from eight HCV patients achieved sustained virological response (SVR). ≥1 non-neutral mutation was found in 24/30 HCV-HIV coinfection and more frequent in SVR group (14 patients). ≥1 non-neutral mutation were found statistically significant for overall SVR achievement (p<0.05) in all patients regardless of coinfection or monoinfection status. Of the 27 HCV-HIV coinfected patients with CC-gene, 21 subjects had non-neutral mutation. The structure which was expected as NS5A binding site structure was different from consensus (wild type) in SVR group, while the structure was similar to consensus in non-SVR group. CONCLUSION: having ≥1 non-neutral mutation was associated with SVR achievement in Peg-IFN/RBV therapy, regardless of monoinfection and coinfection status.


Assuntos
Infecções por HIV/complicações , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferons/genética , Proteínas não Estruturais Virais/genética , Adulto , Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Polietilenoglicóis , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Ribavirina/uso terapêutico , Resposta Viral Sustentada
9.
BMC Infect Dis ; 19(1): 703, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395019

RESUMO

BACKGROUND: Hepatitis C virus (HCV) is a major public health problem in correctional settings. HCV treatment is often not possible in U.S. jails due to short lengths of stay. Linkage to care is crucial in these settings, but competing priorities complicate community healthcare engagement and retention after incarceration. METHODS: We conducted a single arm clinical trial of a combined transitional care coordination (TCC) and patient navigation intervention and assessed the linkage rate and factors associated with linkage to HCV care after incarceration. RESULTS: During the intervention, 84 participants returned to the community after their index incarceration. Most participants were male and Hispanic, with a history of mental illness and a mean age of 45 years. Of those who returned to the community, 26 (31%) linked to HCV care within a median of 20.5 days; 17 (20%) initiated HCV treatment, 15 (18%) completed treatment, 9 (11%) had a follow-up lab drawn to confirm sustained virologic response (SVR), and 7 (8%) had a documented SVR. Among those with follow-up labs the known SVR rate was (7/9) 78%. Expressing a preference to be linked to the participant's existing health system, being on methadone prior to incarceration, and feeling that family or a loved one were concerned about the participant's wellbeing were associated with linkage to HCV care. Reporting drinking alcohol to intoxication prior to incarceration was negatively associated with linkage to HCV care. CONCLUSION: We demonstrate that an integrated strategy with combined TCC and patient navigation may be effective in achieving timely linkage to HCV care. Additional multicomponent interventions aimed at treatment of substance use disorders and increasing social support could lead to further improvement. TRIAL REGISTRATION: Clinicaltrials.gov NCT04036760 July 30th, 2019 (retrospectively registered).


Assuntos
Continuidade da Assistência ao Paciente , Hepatite C/tratamento farmacológico , Prisioneiros/estatística & dados numéricos , Adulto , Serviços de Saúde Comunitária , Feminino , Hepatite C/virologia , Hispano-Americanos , Humanos , Masculino , Metadona/uso terapêutico , Pessoa de Meia-Idade , New York , Navegação de Pacientes , Prisões , Estudos Prospectivos , Transtornos Relacionados ao Uso de Substâncias/terapia , Resposta Viral Sustentada
10.
Braz J Med Biol Res ; 52(8): e8519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31389490

RESUMO

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2-228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2-16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.


Assuntos
Antivirais/administração & dosagem , Hepatite C/tratamento farmacológico , Imidazóis/administração & dosagem , Transplante de Fígado/efeitos adversos , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral
11.
BMC Infect Dis ; 19(1): 640, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324231

RESUMO

BACKGROUND: The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown. METHODS: A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups. RESULTS: Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy. CONCLUSIONS: In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment. TRIAL REGISTRATION: The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970 . Registration date: December 15, 2017.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Adulto , Biomarcadores/sangue , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Humanos , Masculino , Estudos Prospectivos , Recidiva , Resposta Viral Sustentada , Resultado do Tratamento
12.
EBioMedicine ; 46: 227-235, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31345785

RESUMO

BACKGROUND: Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. METHODS: Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed. RESULTS: OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment. CONCLUSIONS: HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR.


Assuntos
Hepacivirus/fisiologia , Hepatite C/patologia , Hepatite C/virologia , Fígado/patologia , Fígado/virologia , Carga Viral , Adulto , Idoso , Antivirais/farmacologia , Antivirais/uso terapêutico , Biópsia , Feminino , Hepatite C/tratamento farmacológico , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , RNA Viral , Resposta Viral Sustentada , Resultado do Tratamento , Adulto Jovem
13.
PLoS Med ; 16(7): e1002874, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31335865

RESUMO

BACKGROUND: Differentiated antiretroviral therapy (ART) delivery models, in which patients are provided with care relevant to their current status (e.g., newly initiating, stable on treatment, or unstable on treatment) has become an essential part of patient-centered health systems. In 2015, the South African government implemented Chronic Disease Adherence Guidelines (AGLs), which involved five interventions: Fast Track Initiation Counseling for newly initiating patients, Enhanced Adherence Counseling for patients with an unsuppressed viral load, Early Tracing of patients who miss visits, and Adherence Clubs (ACs) and Decentralized Medication Delivery (DMD) for stable patients. We evaluated two of these interventions in 24 South African facilities: ACs, in which patients meet in groups outside usual clinic procedures and receive medication; and DMD, in which patients pick up their medication outside usual pharmacy queues. METHODS AND FINDINGS: We compared those participating in ACs or receiving DMD at intervention sites to those eligible for ACs or DMD at control sites. Outcomes were retention and sustained viral suppression (<400 copies/mL) 12 months after AC or DMD enrollment (or comparable time for controls). 12 facilities were randomly allocated to intervention and 12 to control arms in four provinces (Gauteng, North West, Limpopo, and KwaZulu Natal). We calculated adjusted risk differences (aRDs) with cluster adjustment using generalized estimating equations (GEEs) using difference in differences (DiD) with patients eligible for ACs/DMD prior to implementation (Jan 1, 2015) for comparison. For DMD, randomization was not preserved, and the analysis was treated as observational. For ACs, 275 intervention and 294 control patients were enrolled; 72% of patients were female, 61% were aged 30-49 years, and median CD4 count at ART initiation was 268 cells/µL. AC patients had higher 1-year retention (89.5% versus 81.6%, aRD: 8.3%; 95% CI: 1.1% to 15.6%) and comparable sustained 1-year viral suppression (<400 copies/mL any time ≤ 18 months) (80.0% versus 79.6%, aRD: 3.8%; 95% CI: -6.9% to 14.4%). Retention associations were apparently stronger for men than women (men RD: 13.1%, 95% CI: 0.3% to 23.5%; women RD: 6.0%, 95% CI: -0.9% to 12.9%). For DMD, 232 intervention and 346 control patients were enrolled; 71% of patients were female, 65% were aged 30-49 years, and median CD4 count at ART initiation was 270 cells/µL. DMD patients had apparently lower retention (81.5% versus 87.2%, aRD: -5.9%; 95% CI: -12.5% to 0.8%) and comparable viral suppression versus standard of care (77.2% versus 74.3%, aRD: -1.0%; 95% CI: -12.2% to 10.1%), though in both cases, our findings were imprecise. We also noted apparently increased viral suppression among men (RD: 11.1%; 95% CI: -3.4% to 25.5%). The main study limitations were missing data and lack of randomization in the DMD analysis. CONCLUSIONS: In this study, we found comparable DMD outcomes versus standard of care at facilities, a benefit for retention of patients in care with ACs, and apparent benefits in terms of retention (for AC patients) and sustained viral suppression (for DMD patients) among men. This suggests the importance of alternative service delivery models for men and of community-based strategies to decongest primary healthcare facilities. Because these strategies also reduce patient inconvenience and decongest clinics, comparable outcomes are a potential success. The cost of all five AGL interventions and possible effects on reducing clinic congestion should be investigated. CLINICAL TRIAL REGISTRATION: NCT02536768.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Acesso aos Serviços de Saúde , Adesão à Medicação , Infuência dos Pares , Resposta Viral Sustentada , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/provisão & distribução , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Infecções por HIV/virologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Retenção nos Cuidados , África do Sul , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Adulto Jovem
14.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1269-1274, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303600

RESUMO

Sofosbuvir along with ribavirin is being widely used for treatment of HCV in Pakistan but it may show delayed response and reoccurrence of disease in some cases. The aim of the study was to investigate pharmacokinetics and concentration effect analysis of sofosbuvir. HCV patients (n=100) received 400 mg sofosbuvir along with low dose or weight based ribavirin (400 mg). Nonlinear mixed effects modeling (NONMEM) and unpaired t-test were used for the association of concentrations and treatment outcomes. Average day 10 sofosbuvir metabolite BM 331007 concentration was higher in patients having haemoglobin nadir value <10 g/dl compared to the patients having heamoglobin nadir value >10 g/dl (5.34 versus 4.87 pmol/106 cells; p=0.03). The average concentration trends of GS331007 at day 10 was towards being higher in the patients achieved sustained virologic response (SVR) as compare to the patients relapsed (5.19 versus 4.86 pmol/106 cells; p=0.05). Sofosbuvir (GS331007) thresholds concentration (suggested at day 10 through receiver operating characteristic curve) was 5.4 pmol/106 cells for SVR (p=0.05) and haemoglobin nadir cells was 6.3 pmol/106 with sensitivity and specificity of >60%. Dosing simulations shows that 400 mg sofosbuvir twice daily produce day 10 concentration range of 5.4 to 6.7 pmol/106 cells. The range of therapeutic values was identified for HCV patients receiving sofosbuvir in combination with ribavirin for 24 weeks, suggesting a potential pharmaceutical basis for individualized therapeutic dosing.


Assuntos
Antivirais/farmacocinética , Hepatite C/tratamento farmacológico , Ribavirina/farmacologia , Sofosbuvir/farmacocinética , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/sangue , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Sofosbuvir/sangue , Resposta Viral Sustentada
15.
J Formos Med Assoc ; 118(8): 1187-1192, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279502

RESUMO

BACKGROUND: Glecaprevir/pibrentasvir (GLE/PIB) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-world data of GLE/PIB in Asian patients other than Japanese are limited. We thus investigated the effectiveness and safety profile of GLE/PIB in Taiwanese patients with chronic hepatitis C (CHC). METHODS: CHC patients who received 8, 12, or 16 weeks of GLE/PIB between August and October of 2018 were consecutively enrolled. The treatment duration was determined according to drug label. The hepatic fibrosis was staged according to liver histology, transient elastography, fibrosis index based on 4 factors (FIB-4), or findings of ultrasonography/endoscopy. The primary endpoint was sustained virological response at week 12 off therapy (SVR12). The safety profiles were also assessed. RESULTS: A total of 110 CHC patients with 51% of males were enrolled. The median age was 70 years. A majority (82%) of patients were infected with HCV genotype 2. Forty-six (42%) and 64 (58%) patients had advanced hepatic fibrosis and compensated cirrhosis, respectively. Forty-five (41%) non-cirrhotic patients were treated for 8 weeks. The overall SVR12 rates were 100%, regardless of baseline clinical characteristics. The common adverse events (AEs) were pruritus (12%), anorexia (6%), and fatigue (5%). Nine (8%) serious AEs unrelated to GLE/PIB occurred. Three (2%) patients had Grade 3 elevation of total bilirubin level. None had premature treatment termination, hepatic decompensation, or death. CONCLUSION: Interferon-free GLE/PIB regimen is highly effective and safe for Asian chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/virologia , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Quinoxalinas/efeitos adversos , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Taiwan
18.
Infect Dis Clin North Am ; 33(3): 707-742, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31255384

RESUMO

Approximately 20% of people with HIV in the United States prescribed antiretroviral therapy are not virally suppressed. Thus, optimal management of virologic failure has a critical role in the ability to improve viral suppression rates to improve long-term health outcomes for those infected and to achieve epidemic control. This article discusses the causes of virologic failure, the use of resistance testing to guide management after failure, interpretation and relevance of HIV drug resistance patterns, considerations for selection of second-line and salvage therapies, and management of virologic failure in special populations.


Assuntos
Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Gerenciamento Clínico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Infecções por HIV/virologia , Humanos , Resposta Viral Sustentada , Falha de Tratamento , Estados Unidos
19.
Infect Dis Clin North Am ; 33(3): 693-705, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31255385

RESUMO

This review provides a synopsis of key clinical considerations for switching antiretroviral therapy (ART) for individuals with human immunodeficiency virus who have maintained a routinely suppressed viral load. There may be benefits but also risks involved in every ART regimen change, so strategies for prioritizing individuals for a switch based on the specific antiretroviral agents in the regimen are discussed, along with approaches to ensure maintenance of viral suppression after treatment modifications. Controversial and evolving questions in the area of ART switches and simplifications are also considered.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Substituição de Medicamentos/métodos , Infecções por HIV/tratamento farmacológico , Resposta Viral Sustentada , Humanos
20.
Egypt J Immunol ; 26(1): 151-161, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31333005

RESUMO

Hepatitis C virus (HCV) is a major health problem all over the world with the highest prevalence reported in Egypt. Various treatment regimens have been developed over the last years. Interferon (IFN) based regimen was the standard of care regimen and then the IFN-free therapies were emerged. Host innate immunity through the activity of natural killer (NK) cell is one of the major players in competing infections and tumors, by producing perforin and granzymes that cause cytolysis of target cells, or by the production of various cytokines such as natural interferon gamma. Natural cytotoxicity receptors (NCRs), including Nkp30, Nkp44 and Nkp46, are a group of activating receptors that almost have restricted expression on the surface of NK cells and their density correlates with NK cytotoxicity. The role of these cells is not fully elucidated in patients with chronic HCV infection either treatment-naive or treatment experienced. Therefore, this study aimed to investigate the change that occurs in NK cell activity and cytotoxicity in response to successful elimination of HCV from blood after triple therapy with PEG-IFN-α, ribavirin and sofosbuvir. A total of 56 (50 male: 6 female) HCV patients with mean age of 41.6± 12.1 years were included in this study. They were divided into two groups: treatment naive group (20 patients) and the sustained virologic response (SVR) group (36 patients). All patients were investigated for their NK cell profile, NCRs, perforin and granzyme B expression by flow cytometry. Data was expressed as mean fluorescence intensity (MFI). Results revealed significant increase in MFI of granzyme B (P=0.001) and decrease in MFI of NKp30 (P=0.042) in the SVR group as compared to treatment naïve group. These findings indicated that triple therapy of HCV (IFN, Ribavirin and Sofosbuvir) effected NK activation and cytotoxicity.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Células Matadoras Naturais/efeitos dos fármacos , Adulto , Egito , Feminino , Hepacivirus , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Receptor 3 Desencadeador da Citotoxicidade Natural/análise , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada
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