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2.
Liver Int ; 34(4): 558-66, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24131527

RESUMEN

BACKGROUND & AIMS: Host genetic factors could play a primary role in determining risk for cirrhosis development in HCV-infected patients. The aims of this study were to discover new genetic variants associated with this trait and to replicate some associations formerly reported. METHODS: Three hundred and thirty-seven HCV carriers with available data about liver fibrosis status, who initiated treatment with pegylated interferon plus ribavirin, were included. Of them, 77 (22.85%) were cirrhotic. One hundred and forty-four SNPs from 40 genes related to cholesterol metabolism/transport, sustained viral response to HCV therapy, liver fibrosis, or immune response, were genotyped in all samples. Plink software was used to perform univariate association analyses. The results obtained were adjusted by other parameters related to cirrhosis using multivariate logistic regression models. RESULTS: Only the SNP rs12104272, linked to RRAS, SCAF1, IRF3 and BCL2L12 genes, was associated with cirrhosis. It was observed a higher proportion of rs12104272 A allele carriers in the non-cirrhotic group (60.63%) than in the cirrhotic group (38.15%) (adjusted OR = 0.36, 95% CI = 0.180-0.746, P = 0.006). This effect was stronger in the background of rs12979860 CC genotype of IL28B (adjusted OR = 0.069, 95% CI = 0.014-0.349, P = 0.001). CONCLUSION: The rs12104272 SNP could have clinical value to select those individuals at lower risk for cirrhosis development.


Asunto(s)
Portador Sano/virología , Hepatitis C/virología , Cirrosis Hepática/genética , Genotipo , Hepatitis C/genética , Humanos , Factor 3 Regulador del Interferón/genética , Interferón-alfa/uso terapéutico , Interferones , Interleucinas/genética , Cirrosis Hepática/tratamiento farmacológico , Modelos Logísticos , Proteínas Musculares/genética , Oportunidad Relativa , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Proteínas ras/genética
3.
Clin Infect Dis ; 56(11): 1646-53, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23429381

RESUMEN

BACKGROUND: The objective of this study was to determine the impact of sustained virologic response (SVR) to pegylated interferon (peg-IFN) plus ribavirin (RBV) on the incidence of liver-related complications and overall mortality in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: We included in this prospective cohort study 166 coinfected patients with compensated cirrhosis, who received peg-IFN plus RBV, to assess the time from the starting date of HCV therapy to the first hepatic decompensation and death due to any cause. RESULTS: SVR was observed in 43 (25%) individuals. Two (4.6%) patients with SVR developed liver decompensation vs 33 (26.8%) individuals without SVR (P = .002). The incidence of liver-related complications was 0.89 cases per 100 person-years (95% confidence interval [CI], .11-3.1) in SVR patients and 6.4 cases per 100 person-years (95% CI, 4.5-8.9) in non-SVR patients. Factors independently associated with liver decompensation were non-SVR (hazard ratio [HR], 8.1; 95% CI, 1.08-61.5; P = .042) and MELD score ≥9 at baseline (HR, 2.9; 95% CI, 1.2-7.2; P = .016). Two (4.6%) patients with SVR died due to any cause compared with 22 (17.9%) individuals without SVR (P = .02). MELD score ≥9 (HR, 3.1; 95% CI, 1.3-7.7; P = .011) and non-SVR (HR, 8.0; 95% CI, 1.07-61; P = .043) were independently associated with overall mortality. CONCLUSIONS: The achievement of SVR following peg-IFN plus RBV markedly reduces the incidence of liver-related decompensation and the overall mortality in HIV/HCV-coinfected patients with compensated cirrhosis.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/virología , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Cirrosis Hepática/virología , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C/virología , Humanos , Estimación de Kaplan-Meier , Fallo Hepático/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico
4.
Enferm Infecc Microbiol Clin ; 31(7): 424-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23453582

RESUMEN

INTRODUCTION: Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV. METHODS: This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥ 7kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7kPa after starting Peg-IFN/RBV. RESULTS: After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28-42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2-32.4%) at 12 months, and 51.3% (95% CI: 39.9-63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4-16.6%) at 12 months and 11.3% (95% CI: 6-20.7%) at 24 months for those without SVR (p<0.001). For individuals with LSM ≥ 7kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39-13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69-10)] were independently associated with LSM normalization after starting Peg-IFN/RBV. CONCLUSIONS: LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.


Asunto(s)
Antivirales/administración & dosificación , Diagnóstico por Imagen de Elasticidad , Hepatitis C Crónica/diagnóstico por imagen , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Anciano , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Valores de Referencia , Resultado del Tratamiento
5.
Clin Infect Dis ; 55(12): 1719-26, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22955435

RESUMEN

BACKGROUND: The objective of this study was to determine the efficacy of pegylated interferon (peg-IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV)-related compensated liver cirrhosis, as well as the predictors of response in these individuals. METHODS: All subjects enrolled in a prospective cohort of 841 HIV/HCV-coinfected patients who received peg-IFN and RBV and who had a liver biopsy or a liver stiffness measurement within the year before starting peg-IFN plus RBV were included in this study. The sustained virologic response (SVR) rate and predictors of SVR response were analyzed. RESULTS: A total of 629 patients were included in this study; 175 (28%) had cirrhosis. In an intention-to-treat analysis, 44 (25%) patients with cirrhosis and 177 (39%) without cirrhosis achieved SVR (P = .001). Among patients with cirrhosis, SVR was observed in 14%, 47%, and 30% of individuals with HCV genotypes 1, 2-3, and 4, respectively. Discontinuation of therapy owing to adverse events was observed in 30 (17%) individuals with cirrhosis and 37 (8%) subjects without cirrhosis (P = .001). CONCLUSIONS: The efficacy of peg-IFN plus RBV among HIV/HCV-coinfected patients with cirrhosis is lower than in those without cirrhosis, although this antiviral combination still leads to a substantial rate of SVR in those carrying HCV genotype 3. A higher rate of discontinuations of HCV therapy due to adverse events among cirrhotic patients could partially explain the differences in the SVR rate between both populations.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Femenino , Infecciones por VIH/virología , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C/virología , Humanos , Interferón alfa-2 , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Prospectivos , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Estadísticas no Paramétricas , Carga Viral/efectos de los fármacos
6.
J Hepatol ; 56(4): 788-94, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22173157

RESUMEN

BACKGROUND & AIMS: This study aimed at developing a predictive algorithm based on interleukin 28B (IL28B) genotype, hepatitis C virus (HCV) genotype, and plasma HCV-RNA load, which could accurately allow us to define the probability of response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy in HIV/HCV-coinfected patients. METHODS: Five hundred and twenty-one treatment-naive HIV-infected patients, who initiated HCV therapy with Peg-IFN/RBV, were analysed in an on-treatment basis. Patients were categorized as unlikely responders, uncertain responders, and anticipated responders (<20%, 20-60%, and >60% probability to achieve SVR, respectively). RESULTS: HCV genotype, baseline HCV-RNA load, and IL28B genotype were confirmed as independent predictors of SVR in a logistic regression analysis. A stepwise algorithm based on these three variables was created based on 321 patients and evaluated in the remaining 200 patients. Unlikely responders included patients with genotype 1 or 4, HCV-RNA load ≥600,000IU/ml, and rs12979860 non-CC (rate of SVR: 17.3%). Anticipated responders were those with HCV genotype 2-3, patients harboring HCV genotype 4 and IL28B CC, as well as those who simultaneously bore HCV genotype 1, HCV-RNA load <600,000IU/ml, and IL28B CC (rate of SVR 74.1%, 77.8%, and 64.4%, respectively). The area under the receiver operating characteristic curve of the model was 0.77 (0.733-0.814). CONCLUSIONS: The combined use of IL28B genotype, HCV genotype, and HCV-RNA load enables to easily identify patients with a high and very low likelihood of SVR. HCV therapy could be deferred in the latter patients, until more effective options are available, at least if they do not show advanced liver fibrosis.


Asunto(s)
Algoritmos , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Interleucinas/genética , Polietilenglicoles/uso terapéutico , ARN Viral/sangre , Ribavirina/uso terapéutico , Adulto , Antivirales/uso terapéutico , Estudios de Cohortes , Comorbilidad , Quimioterapia Combinada , Femenino , Genotipo , Infecciones por VIH/epidemiología , Hepatitis C/epidemiología , Humanos , Interferón alfa-2 , Interferones , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Análisis de Regresión , Estudios Retrospectivos , Resultado del Tratamiento , Carga Viral
7.
J Antimicrob Chemother ; 66(6): 1351-3, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21415037

RESUMEN

OBJECTIVES: The aim of this study was to evaluate whether the assessment of hepatitis C virus (HCV) RNA serum at 12 weeks after the end of treatment (W12) was as informative as after 24 weeks (W24) for determining sustained virological response (SVR) in HIV/HCV co-infected patients who received a combination of pegylated interferon (PEG-INF) plus ribavirin (PEG-INF/RBV) and had a virological response at the end of treatment. METHODS: Treatment-naive HIV/HCV patients were included in this prospective study if they had completed a full course of therapy with PEG-INF/RBV, had an undetectable serum HCV RNA at the end of treatment and complied with the W12 and W24 schedule for determining HCV RNA. HCV RNA levels were measured using a quantitative PCR assay (detection limit = 15 IU/mL). Positive predictive value (PPV) was defined as the probability of an undetectable serum HCV RNA at W12 and W24 after the end of treatment. RESULTS: Of 186 patients treated during the study period, 104 (55.9%) were included in the study. At W24, 83 (79.8%) patients had an SVR and 21 (20.2%) had a virological relapse. At W12, HCV RNA was undetectable in 83 (79.8%) patients and all of these had SVR. Undetectable HCV RNA at W12 had a 100% PPV [95% confidence interval (CI) 96.5%-100%] for SVR. CONCLUSIONS: Our results show that undetectable HCV RNA at W12 post-treatment has a high PPV for SVR. Testing for HCV RNA at this moment may therefore be considered an appropriate point in time for identifying SVR and relapse in HIV/HCV co-infected patients receiving treatment with PEG-INF/RBV.


Asunto(s)
Quimioterapia Combinada/métodos , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Antivirales/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , ARN Viral/sangre , Proteínas Recombinantes , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Tiempo , Resultado del Tratamiento , Carga Viral/métodos
8.
Clin Infect Dis ; 51(7): 788-95, 2010 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-20804372

RESUMEN

BACKGROUND: Variation in the IL28B gene is associated with sustained virologic response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)-monoinfected patients with genotype 1. Data on other genotypes and on patients coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We aimed to assess the predictive ability of variations in the single-nucleotide polymorphism rs12979860 for SVR in HIV/HCV-coinfected patients, regardless of HCV genotype. METHODS: The rs12979860 genotype was determined by polymerase chain reaction in 154 patients who had received therapy against HCV with pegylated interferon plus ribavirin. RESULTS: rs12979860 genotype was TT in 20 patients (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in patients with genotype CC and in those with genotype TC or TT, according to HCV genotype, were, respectively, 50% and 17% (P < .001) in patients with genotype 1, 80% and 25% (P = .027) in patients with genotype 4, and 93% and 77% (P = .115) in patients with genotype 3. The median (interquartile range) low-density lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73-120 mg/dL) versus 75 mg/dL (55-91 mg/dL) (P = .001) in those with TC or TT. Independent predictors of SVR were HCV genotype 2-3 (odds ratio [OR], 13.98; 95% confidence interval [CI], 4.87-40.1; P < .001), rs12979860 CC (OR, 5.05; 95% CI, 2.04-12.5; P < .001), baseline plasma HCV RNA load of < or =600,000 IU/mL (OR, 1.99; 95% CI, 1.18- 3.34; P = .009), and female sex (OR, 4.28; 95% CI, 1.08-16.96; P = .039). CONCLUSIONS: IL28B gene variations independently predict SVR in HIV/HCV-coinfected patients with HCV genotype 1 and non-genotype 1 HCV infection. The association between rs12979860 and plasma low-density lipoprotein cholesterol suggests that the system low-density lipoprotein ligand/receptor might be involved in the effect of this genotype.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Interleucinas/genética , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Carga Viral , Adulto , Antivirales/uso terapéutico , Femenino , Genotipo , Infecciones por VIH/complicaciones , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/complicaciones , Humanos , Interferón alfa-2 , Interferones , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Proteínas Recombinantes , Resultado del Tratamiento
9.
J Antimicrob Chemother ; 65(10): 2204-11, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20656678

RESUMEN

OBJECTIVES: To evaluate the changes in liver stiffness measurement (LSM) in patients infected by hepatitis C virus (HCV) under pegylated interferon (Peg-IFN) plus ribavirin therapy. METHODS: One hundred and forty-three HCV-infected patients, of whom 97 (68%) were also carrying HIV, who started treatment with Peg-IFN/ribavirin were included in this prospective cohort study. The outcome variable of the study was the change in LSM between baseline and the scheduled date for evaluating sustained virological response (SVR). RESULTS: The median (Q1-Q3) LSM values at baseline and at the SVR assessment date were 8.1 (6.2-11.6) kPa and 6.8 (5.2-9.8) kPa (P<0.001), respectively. The median (Q1-Q3) decrease between both timepoints was -1 (-2.75, 0.3) kPa. The baseline LSM decreased ≥20% in 37 (46%) patients with SVR and in 19 (30%) without SVR (P=0.05). In the linear regression analysis, baseline LSM {beta [standard error (SE)] -0.712 (0.044), P=0.004}, alcohol intake ≥50 g/day [beta (SE) 0.202 (0.030), P=0.014] and achievement of SVR [beta (SE) -0.238 (0.026), P=0.029] were independently associated with changes in LSM. CONCLUSIONS: LSM decreases significantly among patients with chronic HCV infection who achieve SVR with Peg-IFN/ribavirin. These patients show a higher frequency of LSM reduction ≥20% at the date of SVR evaluation.


Asunto(s)
Antivirales/administración & dosificación , Elasticidad , Hepatitis C Crónica/patología , Interferón-alfa/administración & dosificación , Hígado/patología , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferón alfa-2 , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/sangre , Proteínas Recombinantes , Carga Viral
10.
Hepatology ; 50(4): 1056-63, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19670415

RESUMEN

UNLABELLED: A few studies have assessed the observed fibrosis progression between serial liver biopsies (LB) in human immunodeficiency virus (HIV) / hepatitis C virus (HCV)-coinfected patients. Approximately half of the patients progressed at least one fibrosis stage over a short period of time. The risk factors for this fast progression need clarification. Because of this, we evaluated the observed fibrosis progression rates of HIV/HCV-coinfected patients and the risk factors for accelerated progression. Overall, 135 HIV-infected patients with positive serum HCV RNA, without other possible causes of liver disease, who underwent two LB, separated at least by 1 year, were included in this retrospective cohort study. The median (Q1-Q3) time between both LBs was 3.3 (2.0-5.2) years. Patients showed the following changes in fibrosis stage: regression >or =1 stage: 23 (17%), no change: 52 (39%), progression 1 stage: 38 (28%), and progression > or =2 stages: 22 (16%). Seventeen (13%) patients had cirrhosis in the second biopsy. Factors independently associated with progression > or =1 stage were undetectable plasma HIV RNA during the follow-up (relative risk [RR] [95% confidence interval, 95% CI] 0.61 [0.39-0.93], P = 0.03), moderate-to-severe lobular necroinflammation (1.77 [1.16-2.7], P = 0.009), time between biopsies (1.11 [1.08-1.2], P = 0.01), and end of treatment response to anti-HCV therapy (0.41 [0.19-0.88], P = 0.02). CONCLUSION: Fibrosis progresses with high frequency in HIV/HCV-coinfected patients over a period of time of 3 years. Absent-to-mild lobular necroinflammation at baseline, achievement of response with anti-HCV treatment, and effective antiretroviral therapy are associated with slower fibrosis progression.


Asunto(s)
Progresión de la Enfermedad , VIH/patogenicidad , Hepacivirus/patogenicidad , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Hígado/patología , Hígado/virología , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Antivirales/uso terapéutico , Biopsia , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/patología , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polietilenglicoles/uso terapéutico , Estudios Prospectivos , Proteínas Recombinantes , Estudios Retrospectivos , Ribavirina/uso terapéutico , Factores de Riesgo
11.
Clin Infect Dis ; 49(8): e84-91, 2009 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-19772388

RESUMEN

BACKGROUND: The aim of this study was to assess the efficacy and safety of pegylated interferon (IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patients with severe immunodeficiency in a clinical cohort. BACKGROUND. A total of 542 HIV-infected patients receiving treatment with pegylated IFN plus RBV from June 2001 through April 2007 were included in this study. The outcome variables were sustained virologic response (SVR) rate and the emergence of AIDS-defining events during HCV infection therapy. SVR rates among patients with a CD4 cell count 250 cells/mm(3). The association between SVR and potential predictors was analyzed. RESULTS: Ten (26%) of 39 individuals with a baseline CD4 cell count 250 cells/mm(3) and 198 (39%) of 503 with baseline CD4 cell counts >or=250 CD4 cells/mm(3) achieved SVR (P = .09). In a nested case-control study with populations matched at a 1:2 ratio, the SVR rate was 26% in the CD4 cell count 250 cells/mm(3) group and 32% in the CD4 cell count >250 cells/mm(3) group (P = .5). Baseline CD4 cell count (250 cells/mm(3) vs >250 cells/mm(3)) was not associated with SVR in the multivariate analysis. Two (5%) individuals in the CD4 cell count 250 cells/mm(3) group experienced opportunistic events during follow-up. In the CD4 cell count 250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 16 (41%) and 12 (31%) patients, respectively. In the CD4 cell count >250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 29% (P = .1) and 20% (P = .1) of patients, respectively. CONCLUSIONS: The efficacy of pegylated IFN plus RBV in HIV-HCV-coinfected patients with advanced immunosuppression is substantial and not significantly different to that observed in the overall coinfected population. HCV therapy is generally safe in the population of coinfected patients with advanced immunosuppression.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Antivirales/efectos adversos , Recuento de Linfocito CD4 , Femenino , Humanos , Huésped Inmunocomprometido , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Polietilenglicoles/efectos adversos , Proteínas Recombinantes , Ribavirina/efectos adversos , Resultado del Tratamiento , Carga Viral
12.
J Hepatol ; 50(4): 684-92, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19231001

RESUMEN

BACKGROUND/AIMS: To evaluate the possible influence of baseline insulin resistance in sustained virological response. METHODS: One hundred and fifty-five consecutive individuals from a multicentric cohort of HIV/HCV co-infected patients who underwent therapy with pegylated interferon plus ribavirin were included. The main outcome variable was sustained virological response, defined as undetectable plasma HCV RNA at week 24 after the end of the therapy. Insulin resistance was determined using the HOMA method. RESULTS: Sustained virological response was achieved in 55 (36%) patients. Forty-two (38%) patients with a HOMA lower than 4 developed sustained virological response vs 13 (29%) of those with a HOMA above 4 (p=0.27). Analyses restricted to patients harbouring genotype 1 or 4 showed similar rates of sustained virological response among patients with a HOMA below and above 4 [19 (27%) vs 7 (24%); p=0.8]. In the multivariate analysis, genotype 3 [AOR 9.26; 95% CI 3.03-28.30; p<0.0001], a baseline HCV viral load below 600.000IU/mL [AOR 2.97; 95% CI 1.03-8.57; p=0.04] and baseline LDL cholesterol above 100mg/dL [AOR 6.62; 95% CI 1.97-22.19; p=0.002] were independently associated with sustained virological response. CONCLUSIONS: Insulin resistance is not a relevant predictor of sustained virological response to pegylated interferon plus ribavirin in HIV/HCV co-infected patients.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Resistencia a la Insulina , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Índice de Masa Corporal , Femenino , Hepacivirus/genética , Humanos , Interferón alfa-2 , Masculino , Valor Predictivo de las Pruebas , ARN Viral/sangre , Proteínas Recombinantes , Estudios Retrospectivos , Resultado del Tratamiento , Carga Viral
13.
Antivir Ther ; 13(3): 429-37, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18572756

RESUMEN

BACKGROUND: There is little information about the influence of antiretroviral drugs on the antiviral activity of pegylated interferon (PEG-IFN) plus ribavirin (RBV) against hepatitis C virus (HCV). METHODS: All HIV-infected patients with chronic hepatitis C who received first-line PEG-IFN plus RBV were retrospectively analyzed. Only patients in whom virological stopping rules were applied and who did not change their antiretrovirals were chosen. Plasma RBV concentrations were measured at week 4. RESULTS: A total of 493 patients (78% males, mean age 41 years, 78% on antiretroviral therapy, mean CD4+ T-cell count 561 cells/microl) fit the study inclusion criteria. Mean baseline serum HCV RNA was 5.89 log10 IU/ml, 65% were infected by genotypes 1 or 4 and 40% had advanced liver fibrosis (Metavir F3F4). The overall rate of sustained virological response (SVR) was 38%. Factors associated with lack of SVR in the multivariate analyses (odds ratio [95% confidence interval], P-value) were higher baseline serum HCV RNA (2.42 per log10 IU/ml [1.31-4.46], 0.005), HCV genotypes 1 or 4 (5.95 [2.50-14.29], < 0.001) and lower RBV plasma trough concentrations (1.74 per microg/ml [1.15-2.63], 0.009). Interestingly, a trend was noticed for abacavir use (2.22 [0.91-5.40], 0.08), which become significant when only considering the subset of patients with RBV plasma levels < 2.3 microg/ml (7.63 [1.39-41.67], 0.02). CONCLUSIONS: The use of abacavir might interfere with the anti-HCV activity of PEG-IFN plus RBV. As both antivirals are guanosine analogues, an inhibitory competition between abacavir and RBV might explain this observation, which is more prominent in patients with lower RBV exposure.


Asunto(s)
Antivirales/uso terapéutico , Didesoxinucleósidos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Antivirales/sangre , Interacciones Farmacológicas , Quimioterapia Combinada , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/genética , Humanos , Interferón alfa-2 , Masculino , Oportunidad Relativa , ARN Viral/sangre , Proteínas Recombinantes , Estudios Retrospectivos , Ribavirina/sangre , Medición de Riesgo , España , Insuficiencia del Tratamiento , Carga Viral
14.
J Antimicrob Chemother ; 62(4): 793-6, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18567911

RESUMEN

BACKGROUND: Combination of pegylated interferon (Peg-IFN) and ribavirin is the standard treatment for HCV infection in HIV co-infected patients. However, data available on the efficacy of this therapy in co-infected patients who failed a former interferon-based regimen are limited. METHODS: We analysed the efficacy and safety of the Peg-IFN alfa-2a or alfa-2b plus ribavirin combination in a multicentre observational cohort study including 54 HCV/HIV co-infected patients who had failed to respond to or relapsed on interferon-based treatment. The primary efficacy endpoint was the proportion of patients who achieved a sustained virological response (SVR), defined as HCV RNA <50 IU/mL 24 weeks after completion of therapy. RESULTS: By intention-to-treat analysis, 30% of the patients achieved an SVR. Viral eradication by genotype was 18.9% (7/37) genotype 1; 57.1% (8/14) genotype 3 and 33.3% (1/3) genotype 4. The only independent predictor of SVR was genotype 3 (odds ratio: 5.3; 95% confidence interval: 1.4-19.8). Fourteen (38%) patients with genotype 1 had undetectable viral load at week 48 of treatment. Nevertheless, 50% of them relapsed during the follow-up period. Severe adverse events or progression of HIV infection did not occur during the study; however, 39% of the patients required Peg-IFN dose reduction because of intolerance or haematological toxicity. CONCLUSIONS: Combined Peg-IFN and ribavirin achieved a substantial rate of SVR in HCV/HIV co-infected patients who failed a prior standard interferon-based regimen. The decision to retreat any co-infected patient should be individual-based. More aggressive strategies may be necessary to avoid the high relapse rate observed among patients with genotype 1.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/efectos de los fármacos , Hepacivirus/aislamiento & purificación , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , ARN Viral/sangre , Proteínas Recombinantes , Ribavirina/efectos adversos , Resultado del Tratamiento , Carga Viral
15.
J Antimicrob Chemother ; 62(6): 1365-73, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18854330

RESUMEN

OBJECTIVES: To compare the response to hepatitis C virus (HCV) therapy among human immunodeficiency virus (HIV)/HCV co-infected patients receiving a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] backbone consisting of abacavir plus lamivudine with that observed in subjects who receive tenofovir plus lamivudine or emtricitabine. METHODS: A total of 256 subjects, enrolled in a cohort of 948 HIV-infected patients who received pegylated interferon and ribavirin from October 2001 to January 2006, were included in this study. All patients were taking one protease inhibitor or one non-nucleoside reverse transcriptase inhibitor and abacavir plus lamivudine or tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone during HCV therapy. Sustained virological response (SVR) rates in both backbone groups were compared. RESULTS: In an intention-to-treat analysis, 20 out of 70 (29%) individuals under abacavir and 83 out of 186 (45%) under tenofovir showed SVR (P = 0.02). N(t)RTI backbone containing tenofovir was an independent predictor of SVR in the multivariate analysis [adjusted odds ratio (95% CI), 2.6 (1.05-6.9); P = 0.03]. The association between abacavir use and lower SVR was chiefly seen in patients with plasma HCV-RNA load higher than 600 000 IU/mL and genotype 1 or 4. Among patients treated with ribavirin dose <13.2 mg/kg/day, 3 (20%) of those under abacavir versus 22 (52%) under tenofovir reached SVR (P = 0.03), whereas the rates were 31% and 38% (P = 0.4), respectively, in those receiving >/=13.2 mg/kg/day. CONCLUSIONS: HIV-infected patients who receive abacavir plus lamivudine respond worse to pegylated interferon plus ribavirin than those who are given tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone, especially in those receiving lower ribavirin doses.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adenina/análogos & derivados , Adenina/uso terapéutico , Adulto , Sangre/virología , Estudios de Cohortes , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Didesoxinucleósidos/uso terapéutico , Emtricitabina , Femenino , Estudios de Seguimiento , VIH-1/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Humanos , Interferón alfa-2 , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Organofosfonatos/uso terapéutico , Polietilenglicoles , Proteínas Recombinantes , Tenofovir , Resultado del Tratamiento , Carga Viral
16.
Liver Int ; 28(6): 781-6, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18312289

RESUMEN

BACKGROUND: Most of the prevalent cases of hepatitis C virus (HCV) infection are attributable to intravenous drug using. However, a substantial number of individuals, particularly noninjecting drug users (NIDU), report no identifiable source of HCV exposure. This may be interpreted as inaccurate reporting of past intravenous exposure or as the presence of an unidentified source of HCV infection. Because of this, we evaluated the prevalence of and factors associated with HCV infection among NIDU. METHODS: One hundred and eighty-two individuals who were attended from 2003 to 2004 in a drug addiction facility because of noninjecting drug use were included. RESULTS: HCV infection was detected in 23 (12.6%) participants. Sharing the inhalation tube of crack cocaine [adjusted odds ratio (AOR) 3.6, 95% confidence interval (CI) 1.3-9.8, P=0.01], presence of tattoos (AOR 3.5, 95% CI 1.3-9.1, P=0.02) and age >or=34 years (AOR 3.9, 95% CI 1.3-11.6, P=0.01) 3.9 were independently associated with HCV infection. CONCLUSION: The prevalence of HCV infection in NIDU is higher than in general population. HCV infection is more likely among older drug users, those with tattoos and crack cocaine users that share the inhalation implements.


Asunto(s)
Hepacivirus/aislamiento & purificación , Hepatitis C/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Administración por Inhalación , Adulto , Secreciones Corporales/virología , Comorbilidad , Cocaína Crack/administración & dosificación , Estudios Transversales , Contaminación de Equipos , Femenino , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/transmisión , Heroína/administración & dosificación , Humanos , Masculino , Narcóticos/administración & dosificación , Oportunidad Relativa , Prevalencia , ARN Viral/análisis , Asunción de Riesgos , Saliva/virología , Conducta Sexual , España/epidemiología , Trastornos Relacionados con Sustancias/virología
18.
Antivir Ther ; 12(4): 523-9, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17668561

RESUMEN

INTRODUCTION: The clinical applicability of early viral kinetics at week 4 in predicting sustained virological response (SVR) of pegylated interferon (peg-IFN) plus ribavirin (RBV) in HIV/HCV-coinfected patients is unclear. Our objective was to determine if rapid virological response (RVR) at week 4 of therapy with peg-IFN and RBV could predict SVR among HIV/HCV-coinfected patients. METHODS: HIV/HCV-coinfected patients in whom an HCV viral load determination had been carried out at week 4 of therapy were included in the study. The positive predictive value (PPV) and the negative predictive value (NPV) of RVR (undetectable serum HCV RNA at 4 week) for SVR were calculated in the study population. Receiver operating characteristic curves were calculated to determine the best cutoff of HCV RNA decrease to predict treatment failure. RESULTS: A total of 101 HIV/HCV-coinfected patients were included. RVR and SVR were observed in 39 (39%) and in 49 (48%) individuals, respectively. Of patients with RVR, 37/39 patients achieved SVR (PPV: 95%), whereas 50/62 individuals without RVR did not show SVR (NPV: 81%). The highest NPV (96%) was reached by using a cutoff level of HCV RNA decrease of 0.6 log10. By applying this cutoff level, treatment could have been discontinued in 25 (25%) patients. CONCLUSIONS: An undetectable serum HCV RNA determination at week 4 of treatment with peg-IFN plus RBV is a reliable predictor of SVR in HIV/HCV-coinfected patients. In addition, a decrease of HCV RNA less than 0.6 log10 at this point of treatment could identify an appreciable proportion of individuals who will fail to achieve SVR.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepacivirus/fisiología , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , ARN Viral/sangre , Ribavirina/uso terapéutico , Adulto , Antivirales/administración & dosificación , Quimioterapia Combinada , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Polietilenglicoles , Valor Predictivo de las Pruebas , Proteínas Recombinantes , Ribavirina/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento
19.
Antivir Ther ; 12(8): 1225-35, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18240862

RESUMEN

BACKGROUND: Haematological adverse events related to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy could affect the patients' quality of life; however, the risk factors for severe haematological toxicity associated with this therapy in patients coinfected with hepatitis C virus (HCV) and HIV are unclear. The objective of this study was to identify predictors of severe haematological toxicity among HIV-HCV-coinfected patients treated with PEG-IFN plus RBV. METHODS: This retrospective multicentric study included 237 HIV-HCV-coinfected patients on PEG-IFN plus RBV. Predictors of severe anaemia, neutropenia, thrombocytopenia and overall haematological toxicity were analyzed. RESULTS: Eighty (34%) individuals showed an episode of severe haematological toxicity. Severe anaemia, neutropenia and thrombocytopenia occurred in 32 (13%), 42 (18%) and 26 (11%) patients, respectively. In the multivariate analysis, zidovudine use (adjusted odds ratio [AOR] 3.3; 95% confidence interval [CI] 1.6-10; P = 0.001), baseline body weight < 65 kg (AOR 2.5; 95% CI 1.1-5; P = 0.024), cirrhosis (AOR 5; 95% CI 1.6-16.6; P = 0.006), PEG-IFN-alpha2a (AOR 2.7; 95% CI 1.1-6.6; P = 0.029) and pretreatment haemoglobin level < 14 g/dl (AOR 2.7; 95% CI 1.3-5.5; P = 0.005) were associated with any kind of severe haematological toxicity. Likewise, haemoglobin level < 13 g/dl, neutrophil counts < 2,500 cells/mm3 and platelet counts < 175,000 cells/mm3 were independent predictors of severe anaemia, neutropenia and thrombocytopenia, respectively. CONCLUSIONS: Zidovudine treatment, cirrhosis, baseline low body weight, use of PEG-IFN-alpha2a, and baseline haemoglobin level < 14 g/dl are predictors of overall severe haematological toxicity secondary to PEG-IFN plus RBV in HIV-infected individuals. Low pretreatment levels of each haematological series predict a significant decrease of their values during therapy.


Asunto(s)
Antivirales/efectos adversos , Infecciones por VIH/complicaciones , VIH , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/efectos adversos , Polietilenglicoles/efectos adversos , Ribavirina/efectos adversos , Adulto , Anemia/sangre , Anemia/inducido químicamente , Antivirales/administración & dosificación , Biomarcadores/sangre , Quimioterapia Combinada , Femenino , Fibrosis , Infecciones por VIH/tratamiento farmacológico , Humanos , Inyecciones Subcutáneas , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Recuento de Leucocitos , Masculino , Neutropenia/sangre , Neutropenia/inducido químicamente , Recuento de Plaquetas , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes , Estudios Retrospectivos , Ribavirina/administración & dosificación , Factores de Riesgo , España , Trombocitopenia/sangre , Trombocitopenia/inducido químicamente , Zidovudina/uso terapéutico
20.
PLoS One ; 10(12): e0143492, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26640956

RESUMEN

BACKGROUND: Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients. PATIENTS AND METHODS: This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 µg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. RESULTS: Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events. CONCLUSIONS: No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01529073.


Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Tiazoles/administración & dosificación , Adulto , Antivirales/administración & dosificación , Antivirales/efectos adversos , Coinfección/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Nitrocompuestos , Proyectos Piloto , Polietilenglicoles/efectos adversos , ARN Viral/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Ribavirina/efectos adversos , Tiazoles/efectos adversos , Resultado del Tratamiento
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