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Background: Liver fibrosis is a leading cause of morbimortality in people with HIV/hepatitis C virus (HCV). Natural killer (NK) cells are linked with amelioration of liver fibrosis; however, NK cells from individuals coinfected with HIV/HCV with cirrhosis display impaired functionality and high PD-1 expression. Here, we aimed to study PD-1, TIGIT, and Tim3 as potential exhaustion markers in NK cells from persons coinfected with HIV/HCV with mild and advanced liver fibrosis. We also evaluated the role of PD-1 expression on NK cells after HCV clearance by direct-acting antivirals (DAAs). Methods: Peripheral blood mononuclear cells were isolated from individuals coinfected with HIV/HCV (N = 54; METAVIR F0/F1, n = 27; F4, evaluated by transient elastography, n = 27). In 26 participants, samples were collected before, at the end of, and 12 months after successful DAA treatment. The frequency, immunophenotype (PD-1, TIGIT, and Tim3 expression), and degranulation capacity (CD107a assay) of NK cells were determined by flow cytometry. Results: Unlike PD-1, Tim3 and TIGIT were comparably expressed between persons with mild and advanced fibrosis. Degranulation capacity was diminished in NK/TIGIT+ cells in both fibrosis stages, while NK/PD-1+ cells showed a lower CD107a expression in cirrhotic cases. Twelve months after DAA treatment, those with advanced fibrosis showed an improved NK cell frequency and reduced NK/PD-1+ cell frequency but no changes in CD107a expression. In individuals with mild fibrosis, neither PD-1 nor NK cell frequency was modified, although the percentage of NK/CD107a+ cells was improved at 12 months posttreatment. Conclusions: Although DAA improved exhaustion and frequency of NK cells in cirrhotic cases, functionality was reverted only in mild liver fibrosis, remarking the importance of an early DAA treatment.
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Resumen La infección crónica por el virus de la hepatitis C (VHC) afecta a 58 millones de personas y es una importante causa de morbimortalidad alrededor del mundo. La reinfección por VHC es un problema creciente en personas con factores de riesgo como consumo pesado de alcohol, sexo anal, sexo grupal y compartir agujas y jeringas; este tipo de infección se define como un nuevo contagio de VHC con un genotipo viral diferente al de la primera infección en un paciente luego de lograr una respuesta viral sostenida (RVS). La reinfección se presenta, en parte, debido a la ausencia de estrategias de promoción y prevención. Teniendo en cuenta estos antecedentes, se han propuesto estrategias más pragmáticas para controlar la infección por VHC y evitar la reinfección, tales como la microeliminación. En el presente artículo se presenta un caso de un paciente que presenta alteración en los marcadores de la bioquímica hepática, por lo que se solicita una prueba diagnóstica de infección por VHC y luego genotipificación viral, y se evidenció una infección por VHC genotipo 1, subgenotipo 1A. Se inició el manejo con antivirales de acción directa y se documentó una adecuada RVS12. Tres meses después el paciente regresó a consulta y en los exámenes de control se evidenció una carga viral elevada de VHC, por lo que se solicitó genotipificación y se demostró una nueva infección por VHC genotipo 4.
Abstract Chronic hepatitis C (HCV) infection affects 58 million people and is a significant cause of morbidity and mortality worldwide. HCV reinfection is a growing problem in people with risk factors such as heavy alcohol use, anal sex, group sex, and sharing needles and syringes. This type of infection is defined as a new HCV infection with a different viral genotype than the first infection in a patient after achieving a sustained viral response (SVR). Reinfection occurs, in part, due to the absence of promotion and prevention strategies. Taking this background into account, more pragmatic approaches have been proposed to control HCV infection and avoid reinfection, such as micro elimination. This article reports the case of a patient with alterations in biochemical liver markers, for which a diagnostic test for HCV infection and then viral genotyping was requested. Infection by HCV genotype 1, subgenotype 1A, was evidenced. Management with direct-acting antivirals was started, and an adequate SVR12 was documented. Three months later, the patient returned, and the control tests showed a high HCV viral load, for which genotyping was requested, showing a new HCV genotype 4 infection.
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Despite successful HIV suppression by antiretroviral treatment (ART), immune activation may persist in HIV patients, contributing to an impaired immunological reconstitution and disease progression. Information regarding Hepatitis C virus (HCV) coinfection as a factor that accounts for immune activation in HIV subjects remains unclear. Furthermore, most studies have been carried out considering HIV/HCV patients as a whole, without taking into account the presence or absence of liver damage. Therefore, it is unknown if HCV and/or its liver-related disease could act as two independent factors contributing to the immune activation. In this study, we investigated the presence of immune activation in a cohort of 50 HIV/HCV patients by measuring cytokine levels, CD4+ T-cell counts and CD4/CD8 ratios. Six patient groups were defined according to HIV viral load, HCV status, and liver disease to assess the impact of each of these factors on immune activation and reconstitution in HIV/HCV patients. Only subjects with controlled HIV infection and cleared HCV displayed immunological parameters within normal ranges. The mere presence of HCV contributes to immune activation leading to an inappropriate immunological reconstitution. This state exacerbates in the presence of HCV-associated liver disease. Our results suggest that ART is not enough to suppress immune activation in the context of HIV/HCV coinfection, since both HCV and its liver-related disease would contribute to the immune activation. Given that immune activation worsens immunological reconstitution and clinical status, these results support the priority of HCV treatment in HIV/HCV patients and suggest the monitoring of their liver status.
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Antirretrovirais/uso terapêutico , Coinfecção/imunologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Reconstituição Imune , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Relação CD4-CD8 , Estudos Transversais , Citocinas/sangue , HIV/isolamento & purificação , Infecções por HIV/imunologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Non-structural 5A protein (NS5A) resistance-associated substitutions (RASs) have been identified in patients infected with hepatitis C virus (HCV), even prior to exposure to direct-acting antiviral agents (DAAs). Selection for these variants occurs rapidly during treatment and, in some cases, leads to antiviral treatment failure. DAAs are currently the standard of care for hepatitis C treatment in many parts of the world. Nevertheless, in Brazil, the prevalence of pre-existing NS5A RASs is largely unknown. In this study, we evaluated the frequency of naturally occurring NS5A RASs in Brazilian patients infected with HCV as either a monoinfection or coinfection with human immunodeficiency virus (HIV). METHODS: Direct Sanger sequencing of the NS5A region was performed in 257 DAA-naïve patients chronically infected with HCV (156 monoinfected with HCV and 101 coinfected with HIV/HCV). RESULTS: The frequencies of specific RASs in monoinfected patients were 14.6% for HCV GT-1a (M28 V and Q30H/R), 6.0% for GT-1b (L31F/V and Y93H), and 22.6% for GT-3a (A30K and Y93H). For HIV/HCV-coinfected patients, the frequencies of RAS were 3.9% for GT-1a (M28 T and Q30H/R), and 11.1% for GT-1b (Y93H); no RASs were found in GT-3a sequences. CONCLUSIONS: Substitutions that may confer resistance to NS5A inhibitors exist at baseline in Brazilian DAA-naïve patients infected with HCV GT-1a, -1b, and -3a. Standardization of RAS definitions is needed to improve resistance analyses and to facilitate comparisons of substitutions reported across studies worldwide. Therapeutic strategies should be optimized to efficiently prevent DAA treatment failure due to selection for RASs, especially in difficult-to-cure patients.
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Antivirais/farmacologia , Farmacorresistência Viral/genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Proteínas não Estruturais Virais/genética , Substituição de Aminoácidos , Antivirais/uso terapêutico , Brasil/epidemiologia , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Prevalência , Falha de TratamentoRESUMO
Introducción: Las terapias contra el virus de la Hepatitis C han evolucionado vertiginosamente con el desarrollo de los antivirales de acción directa (AADs). Los nuevos regímenes han conseguido igualar las tasas de respuesta al tratamiento en los monoinfectados y los coinfectados con VIH, una población tradicionalmente difícil de tratar debido a la elevada morbimortalidad hepática y sistémica, reacciones adversas e interacciones medicamentosas. Objetivo: Analizar las opciones farmacoterapéuticas más modernas disponibles para los pacientes coinfectados con VIH y VHC, con énfasis en los nuevos antivirales de acción directa, a fin de ofrecer una herramienta útil en el abordaje terapéutico en estos pacientes. Material y métodos: Se revisaron artículos originales, ensayos clínicos y revisiones sistemáticas hasta septiembre de 2016, bases de datos internacionales de interacciones medicamentosas y Guías de Práctica Clínica actualizadas. Desarrollo: Las terapias contra el virus de la Hepatitis C (VHC) han evolucionado vertiginosamente con el desarrollo de los antivirales de acción directa (AADs). Los nuevos regímenes han conseguido igualar las tasas de respuesta al tratamiento en los monoinfectados y los coinfectados con VIH, una población tradicionalmente difícil de tratar que, además, asociaba una elevada morbimortalidad hepática y sistémica, más reacciones adversas y complejas interacciones medicamentosas. Conclusiones: En este nuevo escenario es fundamental dedicar esfuerzos a identificar el elevado porcentaje de infectados no diagnosticados, potenciales interacciones, especialmente con fármacos para patologías asociadas al envejecimiento de los pacientes, reacciones adversas a medio-largo plazos y desarrollo de resistencias, además de garantizar la cobertura universal en todos los contextos clínicos(AU)
Introduction:Therapies for hepatitis C virus (HCV) have rapidly evolved with the development of direct-acting antiviral agents. New regimens, achieve an equate response rates to treatment in cases of HCV mono-infected and HIV/HCV co-infected; a population traditionally difficult to treat due to a high hepatic and systemic morbidity-mortality, adverse reactions and drug interactions. Objective: To analyse the current Pharma-therapeutic options available for co-infected HIV-HCV patients, with emphasis I the new direct-acting antiviral agents, in order to offer a useful tool for the therapeutic approach in these patients. Material and Methods: Original articles, clinical studies and systematic reviews until September 2016 were carried out, as well as international drug interactions databases and updated Practical Guidelines. Development: Therapies for hepatitis C virus (HCV) have rapidly evolved with the development of direct-acting antiviral agents. New regimens achieve an equate response rates to treatment in HCV mono-infected and HIV/HCV co-infected; a population traditionally difficult to treat, which also associate a high hepatic and systemic morbidity-mortality, adverse reactions and complex drug interactions. Conclusions: In this new scenario efforts must be addressed to identify the high percentage of undiagnosed patients; potential interactions, especially with drugs related with patient aging; medium and long-term adverse reactions and development of drug resistances, as well as to guarantee universal coverage in all clinical contexts(AU)
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Humanos , Masculino , Feminino , Comorbidade , Infecções por HIV/terapia , Hepatite C Crônica/terapia , Hepacivirus/patogenicidade , Coinfecção/epidemiologiaRESUMO
To evaluate the associations of HPA polymorphisms -1, -3, and -5 with HIV/HCV coinfection were included in this study 60 HIV/HCV-coinfected patients from the Sao Paulo State health service centers. Data reported by Verdichio-Moraes et al. (2009: J. Med Virol 81:757-759) were used as the non-infected and HCV monoinfected groups. Human Platelet Polymorphism genotyping was performed in 60 Patients co-infected with HIV/HCV by PCR-SSP or PCR-RFLP. HIV subtyping and HCV genotyping was performed by RT-PCR followed sequencing. The data analyses were performed using the χ2 test or Fisher's Exact Test and the logistic regression model. Patients coinfected with HIV/HCV presented HCV either genotype 1 (78.3%) or non-1 (21.7%) and HIV either subtype B (85.0%) or non-B (15%). The Human Platelet Polymorphism-1a/1b genotype was more frequent (P < 0.05) in HIV/HCV coinfection than in HCV monoinfection and the allelic frequency of Human Platelet Polymorphism-5b in the Patients coinfected with HIV/HCV was higher (P < 0.05) than in HCV monoinfected cases and non-infected individuals. These data suggest that the presence of specific HPA allele on platelets could favor the existence of coinfection. On the other hand, Human Platelet Polymorphism-5a/5b was more frequent (P < 0.05) in HIV/HCV coinfected and HCV monoinfected groups than in the non-infected individuals, suggesting that this platelet genotype is related to HCV infection, regardless of HIV presence. Results suggest that the Human Platelet Polymorphism profile in HIV/HCV coinfected individuals differs from the one of both HCV monoinfected and non-infected population. So, the Human Platelet Polymorphism can be a genetic marker associated with HIV/HCV coinfection.
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Antígenos de Plaquetas Humanas/genética , Coinfecção , Infecções por HIV/complicações , Hepatite C/complicações , Hepatite C/genética , Polimorfismo Genético , Adulto , Coinfecção/genética , Feminino , Marcadores Genéticos , Genótipo , Infecções por HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNARESUMO
Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.
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Hemofilia A/complicações , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Hepatite C/virologia , Leucócitos Mononucleares/virologia , Adulto , Idoso , Coinfecção/virologia , Genótipo , Infecções por HIV/complicações , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To evaluate changes in liver histology in patients with human immunodeficiency virus/hepatitis C virus coinfection non-responders to a suboptimal Interferon+Ribavirine regimen. MATERIALS AND METHODS: We investigated 49 patients with two sequential liver biopsies: 18 were non-responders to Interferon+Ribavirine treatment (Group hepatitis C virus Rx) administered after the 1st liver biopsy who underwent a 2nd liver biopsy after a median period of 3.92 year and 31 were patients who remained untreated for hepatitis C virus disease (Group hepatitis C virus untreated) after the 1st liver biopsy because of refusal and underwent a 2nd liver biopsy after a median period of 5.05-years. Most patients in both groups were under highly active antiretroviral therapy. At the time of 1st liver biopsy similar degrees of necro-inflammation, fibrosis and steatosis were observed in both groups. Changes in liver lesions between 1st and 2nd liver biopsys were adjusted for different intervals between liver biopsys by a mathematic formula. RESULTS: Liver fibrosis did not change in 88.9% of patients in Group hepatitis C virus Rx and in 77.4% in Group hepatitis C virus untreated. A marked deterioration in liver fibrosis was observed in 5 (16%) patients in Group hepatitis C virus untreated and in none in Group hepatitis C virus treated. Necro-inflammation and steatosis remained substantially unchanged in both groups. CONCLUSION: Liver histology remained substantially unchanged in human immunodeficiency virus/hepatitis C virus patients non-responder to anti-hepatitis C virus therapy over 4 years observation, suggesting an effective anti-hepatitis C virus early treatment for all hepatitis C virus/human immunodeficiency virus coinfected patients who can reasonably tolerate therapy. .
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Adulto , Feminino , Humanos , Masculino , Antivirais/uso terapêutico , Coinfecção , Infecções por HIV/patologia , Hepatite C/patologia , Interferon-alfa/uso terapêutico , Cirrose Hepática/virologia , Fígado/patologia , Ribavirina/uso terapêutico , Antivirais/efeitos adversos , Biópsia , Coinfecção/patologia , Coinfecção/virologia , Progressão da Doença , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/efeitos adversos , Cirrose Hepática/patologia , Fígado/virologia , Ribavirina/efeitos adversos , Índice de Gravidade de DoençaRESUMO
AIM: To evaluate changes in liver histology in patients with human immunodeficiency virus/hepatitis C virus coinfection non-responders to a suboptimal Interferon+Ribavirine regimen. MATERIALS AND METHODS: We investigated 49 patients with two sequential liver biopsies: 18 were non-responders to Interferon+Ribavirine treatment (Group hepatitis C virus Rx) administered after the 1st liver biopsy who underwent a 2nd liver biopsy after a median period of 3.92 year and 31 were patients who remained untreated for hepatitis C virus disease (Group hepatitis C virus untreated) after the 1st liver biopsy because of refusal and underwent a 2nd liver biopsy after a median period of 5.05-years. Most patients in both groups were under highly active antiretroviral therapy. At the time of 1st liver biopsy similar degrees of necro-inflammation, fibrosis and steatosis were observed in both groups. Changes in liver lesions between 1st and 2nd liver biopsys were adjusted for different intervals between liver biopsys by a mathematic formula. RESULTS: Liver fibrosis did not change in 88.9% of patients in Group hepatitis C virus Rx and in 77.4% in Group hepatitis C virus untreated. A marked deterioration in liver fibrosis was observed in 5 (16%) patients in Group hepatitis C virus untreated and in none in Group hepatitis C virus treated. Necro-inflammation and steatosis remained substantially unchanged in both groups. CONCLUSION: Liver histology remained substantially unchanged in human immunodeficiency virus/hepatitis C virus patients non-responder to anti-hepatitis C virus therapy over 4 years observation, suggesting an effective anti-hepatitis C virus early treatment for all hepatitis C virus/human immunodeficiency virus coinfected patients who can reasonably tolerate therapy.
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Antivirais/uso terapêutico , Coinfecção , Infecções por HIV/patologia , Hepatite C/patologia , Interferon-alfa/uso terapêutico , Cirrose Hepática/virologia , Fígado/patologia , Ribavirina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Biópsia , Coinfecção/patologia , Coinfecção/virologia , Progressão da Doença , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Humanos , Interferon-alfa/efeitos adversos , Fígado/virologia , Cirrose Hepática/patologia , Masculino , Ribavirina/efeitos adversos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The purpose of this study was to update the epidemiological data on the prevalence of coinfection with hepatitis C virus (HCV) and HIV, and to identify whether specific clinical and epidemiological factors influenced the response of HIV-positive adults to highly active antiretroviral therapy (HAART). METHODS: This retrospective observational cohort study of 238 HIV-infected patients evaluated the effect of different epidemiological and clinical parameters (including HCV coinfection) on therapy response among HIV-infected adults initiating HAART. Multiple logistic regression models were used to identify factors associated with therapy response and estimated risk coefficients. RESULTS: Seroprevalence of HCV infection in this population was 26% (62/238). We did not observe a significant association between immunological or virological response relating to patient gender or HAART regimen. However, this analysis showed that HCV serological status, age at HIV diagnosis, duration of treatment and WHO clinical stage of AIDS (<200 CD4 cells/ml independently of viral load either < or > to 100,000 copies/ml), were significantly associated with immunological and virological responses to HAART. CONCLUSIONS: These results show further evidence that hepatitis C serostatus is associated with a reduced response to HAART.
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Terapia Antirretroviral de Alta Atividade , Coinfecção/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Adulto , Idoso , Argentina/epidemiologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Coinfecção/imunologia , Coinfecção/virologia , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Hepatite C/imunologia , Hepatite C/virologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estudos Soroepidemiológicos , Carga Viral , Adulto JovemRESUMO
OBJECTIVES: Progression of hepatic fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C virus compared to hepatitis C virus mono-infected patients. This study aimed to compare ultrasound features and selected clinical and biochemical variables between patients with human immunodeficiency virus/hepatitis C virus co-infection (n = 16) versus hepatitis C virus mono-infection (n = 16). METHODS: Each patient underwent abdominal ultrasound, and a specific evaluation was performed in order to detect findings consistent with chronic liver disease. Characterization of spleen size, liver structural pattern, diameter of the portal, spleen, and mesenteric veins was based on classical ultrasound parameters. Propensity score was used for control of selection bias and performed using binary logistic regression to generate a score for each patient. The Fisher and Mann-Whitney tests were used to evaluate categorical variables and continuous variables, respectively. RESULTS: On univariate analysis right hepatic lobe size was larger in human immunodeficiency virus/hepatitis C virus patients (157.06 ± 17.56 mm) compared to hepatitis C virus mono-infected patients (134.94 ± 16.95 mm) (p = 0.0011). The left hepatic lobe was also significantly larger in human immunodeficiency virus/hepatitis C virus patients Cirrhosis (115.88 ±22.69 mm) versus hepatitis C virus mono-infected patients (95.06 ±24.18 mm) (p= 0.0177). Also, there was a strong correlation between hepatomegaly and co-infection (p=0.005). CONCLUSION: Human immunodeficiency virus infection was the primary variable influencing liver enlargement in this population. Hepatomegaly on ultrasound was more common among cirrhotic human immunodeficiency virus/hepatitis C virus co-infected patients than among cirrhotic hepatitis C virus mono-infected patients. This aspect is very important in the management of human immunodeficiency virus/hepatitis C virus co-infected patients, because screening for hepatocellular carcinoma is necessary in this population.
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatomegalia , Cirrose Hepática , Análise de Variância , Biópsia , Estudos de Casos e Controles , Coinfecção/patologia , Progressão da Doença , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Hepatomegalia/patologia , Cirrose Hepática/patologia , Tamanho do Órgão , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: The aim of this study was to evaluate the therapeutic response of hepatitis C in patients coinfected with human immunodeficiency virus (HIV-1). METHODS: A retrospective study of 20 patients coinfected with HIV-1/HCV who were treated in the outpatient liver clinic at the Sacred House of Mercy Foundation Hospital of Pará (Fundação Santa Casa de Misericórdia do Pará - FSCMPA) from April 2004 to June 2009. Patients were treated with 180µg PEG interferon-α2a in combination with ribavirin (1,000 to 1,250mg/day) for 48 weeks. The end point was the sustained virological response (SVR) rate (HCV RNA negative 24 weeks after completing treatment). RESULTS: The mean age of the patients was 40±9.5 years, of which 89% (n=17) were male, and the HCV genotypes were genotype 1 (55%, n=11/20), genotype 2 (10%, n=2/20) and genotype 3 (35%, n=7/20). The mean CD4+ lymphocyte count was 507.8, and the liver fibrosis stages were (METAVIR) F1 (25%), F2 (55%), F3 (10%) and F4 (10%). The early virological response (EVR) was 60%, the end-of-treatment virological response (EOTVR) was 45% and the SVR was 45%. CONCLUSIONS: The median HCV viral load was high, and in 85% of cases in which highly active antiretroviral therapy (HAART) was used, none of the patients with F3-F4 fibrosis responded to treatment. Of the twenty patients treated, 45% achieved SVR and 45% achieved EOTVR. Studies that include cases from a wider region are needed to better evaluate these findings.
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Adulto , Feminino , Humanos , Masculino , Antivirais/uso terapêutico , Coinfecção/virologia , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Quimioterapia Combinada , Genótipo , Infecções por HIV/complicações , Hepatite C/complicações , Estudos Retrospectivos , RNA Viral , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Maternal human immunodeficiency virus (HIV) coinfection has been associated with increased hepatitis C virus (HCV) mother-to-child transmission (MTCT). We hypothesized that HCV/HIV-coinfected women with well-controlled HIV disease would not have increased HCV MTCT. METHODS: The NISDI Perinatal and LILAC cohorts enrolled HIV-infected pregnant women and their infants in Latin America and the Caribbean. This substudy evaluated the HCV infection status of mothers at participating sites and their live born, singleton infants who had a 6-month postnatal visit by December 31, 2008. Mothers who were anti-HCV-positive, or who had CD4 counts (cells/mm(3)) <200 with detectable HCV RNA, were considered HCV-infected. All HCV-infected women were tested for HCV RNA. Infants with HCV RNA were considered HCV-infected. RESULTS: Of 1042 enrolled women, 739 (71%) mother-infant pairs met the inclusion criteria. Of the 739 women, 67 (9%) were anti-HCV-positive and 672 anti-HCV-negative [68 (10%) with CD4 counts <200; of these, 3 (4.4%) were HCV RNA-positive]. Therefore, our study population comprised 70 HCV-infected (47 with HCV RNA) and 669 HCV-uninfected women (and their infants). Factors associated with maternal HCV infection included unemployment (odds ratio [OR] = 2.58); tobacco (OR = 1.73) or marijuana (OR = 3.88) use during pregnancy; enrollment HIV viral load ([VL] copies/mL) ≥10 000 (OR = 2.27); HIV clinical disease stage C (OR = 2.12); and abnormal alanine aminotransferase (OR = 4.24) or aspartate aminotransferase (OR = 11.98). Four of 47 infants (8.5%) born to HCV-viremic women were HCV-infected, and all 4 mothers had HIV VL <1000 at hospital discharge after delivery. CONCLUSIONS: HCV MTCT among HIV/HCV-coinfected women with well-controlled HIV disease may be lower than reported in other coinfected populations. Studies with longer infant follow-up are needed.
RESUMO
OBJETIVO: Determinar la evolución clinico-inmunológica de pacientes coinfectados con los virus VIH-VHC, atendidos en el Instituto de Medicina Tropical Dr. Pedro Kourí, entre los años 2002-2006. MÉTODOS: Se realizó un estudio de cohorte prospectivo donde fueron incluidos 170 pacientes: 40 coinfectados con los virus VIH-VHC (expuestos) y 130 infectados con el VIH (no expuestos). RESULTADOS: La edad media fue de 33,4 años (34,1 años en los pacientes expuestos y 33,4 en los no expuestos). Predominaron el sexo masculino y el color blanco de la piel (143: 84,1 por ciento y 94: 55,3 por ciento, respectivamente). Los niveles de transaminasas glutamicooxalacética (TGO), glutámico-pirúvica (TGP) y deshidrogenasa láctica (LDH) fueron más elevados en los pacientes coinfectados (p<0,05) que en los monoinfectados. El tiempo medio de diagnóstico del VIH se relacionó de manera significativa con el diagnóstico de VHC y con el SIDA. Hubo menos casos con conteo de CD4+ por debajo de 200 cel/mm³ en los expuestos que en los no expuestos y no existieron diferencias significativas cuando se compararon los grupos según los niveles de CD4+ mayores de 200 cel/mm³. No hubo diferencias significativas entre los valores medios de CD4+ según el tiempo de diagnostico del VIH entre ambos grupos de pacientes. CONCLUSIONES: El daño tisular reflejado por un aumento del nivel de transaminasas (TGO y TGP) y de deshidrogenasa lßctica (LDH) es más elevado en los pacientes infectados con HVC, y la coinfección por el VHC no se relaciona con un mayor deterioro inmunológico ni con un aumento de la frecuencia del SIDA(AU)
OBJECTIVE: To determine the immunological-clinical course of HIV-CHV coinfected patients, seen in the Pedro Kourí Tropical Medicine Institute between 2002-2006 years. METHODS: A prospective study was conducted including 170 patients: 40 coinfected with HIV-CHV virus (exposed) and 130 infected by HIV virus (no exposed). RESULTS: The mean age was of 33,4 years (34,1 years in exposed patients and 33,4 in those no exposed). There was predominance of white male sex (143: 84,1 percent and dd94: 55,3 percent, respectively. The glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic (GPT) and lactic dehydrogenase (LDH) levels were higher in coinfected patients (p < 0,05) than those monoinfected. The mean time of HIV diagnosis was significantly related to the C hepatitis virus (CHV) and t AIDS. There were less cases with a CD4+ count under 200 cel/mm3 in those exposed that in those no exposed and there were not significant differences when were compared with the groups according to the DC4+ over 200 cel/mm3. Also, there were not marked differences among the mean values of CD43 according to the HIV diagnosis time among both groups of patients. CONCLUSIONS: The tissue damage reflected by an increase of transaminase levels (GOT and PGT) and of lactic dehydrogenase (LDH) is higher in the C hepatitis virus and the coinfection by CHV it is neither related to the great immunologic deterioration nor an increase of AIDS frequency(AU)
Assuntos
Humanos , Masculino , Adulto , Hepacivirus/patogenicidade , Infecções por HIV/complicações , Estudos Prospectivos , Estudos de CoortesRESUMO
OBJETIVO: Determinar la evolución clinico-inmunológica de pacientes coinfectados con los virus VIH-VHC, atendidos en el Instituto de Medicina Tropical Dr. Pedro Kourí, entre los años 2002-2006. MÉTODOS: Se realizó un estudio de cohorte prospectivo donde fueron incluidos 170 pacientes: 40 coinfectados con los virus VIH-VHC (expuestos) y 130 infectados con el VIH (no expuestos). RESULTADOS: La edad media fue de 33,4 años (34,1 años en los pacientes expuestos y 33,4 en los no expuestos). Predominaron el sexo masculino y el color blanco de la piel (143: 84,1 por ciento y 94: 55,3 por ciento, respectivamente). Los niveles de transaminasas glutamicooxalacética (TGO), glutámico-pirúvica (TGP) y deshidrogenasa láctica (LDH) fueron más elevados en los pacientes coinfectados (p<0,05) que en los monoinfectados. El tiempo medio de diagnóstico del VIH se relacionó de manera significativa con el diagnóstico de VHC y con el SIDA. Hubo menos casos con conteo de CD4+ por debajo de 200 cel/mm³ en los expuestos que en los no expuestos y no existieron diferencias significativas cuando se compararon los grupos según los niveles de CD4+ mayores de 200 cel/mm³. No hubo diferencias significativas entre los valores medios de CD4+ según el tiempo de diagnostico del VIH entre ambos grupos de pacientes. CONCLUSIONES: El daño tisular reflejado por un aumento del nivel de transaminasas (TGO y TGP) y de deshidrogenasa lßctica (LDH) es más elevado en los pacientes infectados con HVC, y la coinfección por el VHC no se relaciona con un mayor deterioro inmunológico ni con un aumento de la frecuencia del SIDA
OBJECTIVE: To determine the immunological-clinical course of HIV-CHV coinfected patients, seen in the Pedro Kourí Tropical Medicine Institute between 2002-2006 years. METHODS: A prospective study was conducted including 170 patients: 40 coinfected with HIV-CHV virus (exposed) and 130 infected by HIV virus (no exposed). RESULTS: The mean age was of 33,4 years (34,1 years in exposed patients and 33,4 in those no exposed). There was predominance of white male sex (143: 84,1 percent and dd94: 55,3 percent, respectively. The glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic (GPT) and lactic dehydrogenase (LDH) levels were higher in coinfected patients (p < 0,05) than those monoinfected. The mean time of HIV diagnosis was significantly related to the C hepatitis virus (CHV) and t AIDS. There were less cases with a CD4+ count under 200 cel/mm3 in those exposed that in those no exposed and there were not significant differences when were compared with the groups according to the DC4+ over 200 cel/mm3. Also, there were not marked differences among the mean values of CD43 according to the HIV diagnosis time among both groups of patients. CONCLUSIONS: The tissue damage reflected by an increase of transaminase levels (GOT and PGT) and of lactic dehydrogenase (LDH) is higher in the C hepatitis virus and the coinfection by CHV it is neither related to the great immunologic deterioration nor an increase of AIDS frequency
Assuntos
Humanos , Masculino , Adulto , Hepacivirus/patogenicidade , Infecções por HIV/complicações , Estudos de Coortes , Estudos ProspectivosRESUMO
A polineuropatia desmielinizante inflamatória cônica possui forte associação com a infecção pelo HIV e HCV. Uma rara associação entre PDIC e o tratamento da hepatite C com interferon peguilado alfa foi descrita recentemente. Nós descrevemos o primeiro caso de polineuropatia desmielinizante inflamatória crônica em um paciente branco, sexo masculino infectado por HIV e HCV associado a interferon peguilado alfa 2b. O paciente recuperou-se completamente após o uso de imunoglobulina hiperimune endovenosa. Infectologistas e hapatologistas devem estar atentos à esta rara e grave associação, que exige imediata descontinuação da droga e tratamento precoce.
Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/efeitos adversos , Interferon-alfa , Imunoglobulinas Intravenosas/uso terapêutico , Polietilenoglicóis/efeitos adversos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/induzido quimicamente , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológicoRESUMO
The potential impact of the hepatitis C virus (HCV) on clinical, immunological and virological responses to initial highly active antiretroviral therapy (HAART) of patients infected with human immunodeficiency virus (HIV) is important to evaluate due to the high prevalence of HIV-HCV coinfection. A historical cohort study was conducted among 824 HIV-infected patients starting HAART at a public referral service in Belo Horizonte, Brazil, to assess the impact of HCV seropositivity on appearance of a new AIDS-defining opportunistic illness, AIDS-related death, suppression of viral load, and an increase in CD4-cell count. A total of 76 patients (9.2 percent) had a positive HCV test, 26 of whom (34.2 percent) had a history of intravenous drug use. In multivariate analysis, HCV seropositivity was associated with a smaller CD4-cell recovery (RH=0.68; 95 percent CI [0.49-0.92], but not with progression to a new AIDS-defining opportunistic illness or to AIDS-related death (RH=1.08; 95 percent CI [0.66-1.77]), nor to suppression of HIV-1 viral load (RH=0.81; 95 percent CI [0.56-1.17]) after starting HAART. These results indicate that although associated with a blunted CD4-cell recovery, HCV coinfection did not affect the morbidity or mortality related to AIDS or the virological response to initial HAART.