RESUMO
This study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIV-infected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load -10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin -IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Células Dendríticas/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV-1/imunologia , Células Mieloides/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/farmacologia , Contagem de Células Sanguíneas , Células Dendríticas/imunologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Estudos Prospectivos , Linfócitos T Reguladores , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Carga Viral/imunologiaRESUMO
UNLABELLED: Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01437241.
Assuntos
Regulação Viral da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Piridazinas/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Terapia de Salvação/métodos , Quimioterapia Combinada , Determinação de Ponto Final , Humanos , Estimativa de Kaplan-Meier , Nitrilas , Piridazinas/efeitos adversos , Piridazinas/uso terapêutico , Pirimidinas , RNA Viral/metabolismo , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Espanha , Resultado do TratamentoAssuntos
Antivirais/administração & dosagem , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Prolina/análogos & derivados , Ribavirina/administração & dosagem , Feminino , Humanos , MasculinoRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/virologia , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Cirrose Hepática/virologia , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C/virologia , Humanos , Estimativa de Kaplan-Meier , Falência Hepática/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Proteínas Recombinantes/uso terapêuticoRESUMO
We assessed the relationship between atazanavir (ATV)-based antiretroviral treatment (ART) and plasma hepatitis C virus (HCV) viral load in a population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients who received ART based on a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) were included. Patients were stratified by ART drug [ATV/rtv, lopinavir (LPV/rtv), efavirenz (EFV), nevirapine (NVP), and other PIs], HCV genotype (1/4 and 2/3), and IL28B genotype (CC and non-CC). The Kruskal-Wallis test and chi-squared test were used to compare continuous and categorical variables, respectively. Multivariate analysis consisted of a stepwise linear regression analysis. Six hundred and forty-nine HIV/HCV-coinfected patients were included. HCV genotype 1/4 patients who received ATV had higher HCV RNA levels [6.57 (5.9-6.8) log IU/ml] than those who received LPV [6.1 (5.5-6.5) log IU/ml], EFV [6.1 (5.6-6.4) log IU/ml], NVP [5.8 (5.5-5.9) log IU/ml], or other PIs [6.1 (5.7-6.4) log IU/ml] (p=0.014). This association held for the IL28B genotype (CC versus non-CC). The association was not found in patients carrying HCV genotypes 2/3. The linear regression model identified the IL28B genotype and ATV use as independent factors associated with HCV RNA levels. ATV-based therapy may be associated with a higher HCV RNA viral load in HIV/HCV-coinfected patients.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Oligopeptídeos/administração & dosagem , Piridinas/administração & dosagem , Carga Viral , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Sulfato de Atazanavir , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genéticaRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Feminino , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/virologia , Humanos , Interferon alfa-2 , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Prospectivos , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Estatísticas não Paramétricas , Carga Viral/efeitos dos fármacosRESUMO
We assess the efficacy of pegylated interferon (peg-IFN) with ribavirin (RBV) and the predictors of sustained virological response (SVR) among HIV/hepatitis C virus genotype 4 (HCV-4)-coinfected patients. Thirty-nine (31.5%) of 124 individuals with HCV-4 achieved SVR compared with 103 (22.7%) of 453 individuals with HCV genotype 1 (P=0.046). Only interleukin-28B (IL28B) genotype CC was independently associated with SVR in HIV/HCV-4-coinfected patients. The efficacy of peg-IFN with RBV in coinfected individuals with genotype 4 is significantly higher than in those with genotype 1. IL28B CC genotype is the main predictor of response in this population.
Assuntos
Antivirais/farmacologia , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Interferon-alfa/farmacologia , Polietilenoglicóis/farmacologia , Ribavirina/farmacologia , Coinfecção , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Humanos , Masculino , Proteínas Recombinantes/farmacologia , Resultado do TratamentoRESUMO
UNLABELLED: Hepatic steatosis (HS) is frequent in human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients. Antiretroviral therapy (ART) and metabolic alterations could induce HS. However, a protective effect of ART has been reported in a paired biopsy study. Thus, our aim was to examine the changes and predictors of HS progression among HIV/HCV-coinfected patients with sequential biopsies. We also evaluated the rates of steatohepatitis and factors associated thereof. HIV-infected patients with detectable serum HCV RNA, who underwent two biopsies, separated at least by 1 year, were included in this retrospective study. HS progression was defined as increase in one or more HS grades. The median (interquartile range) time between biopsies was 3.3 (2.0-5.2) years. Among 146 individuals, HS at baseline was observed in 86 (60%) patients and in 113 (77%) in the follow-up biopsy (P < 0.001). Progression of HS was observed in 60 (40%) patients. HS regressed in 11 (8%) patients. Factors associated with HS progression were changes in fasting plasma glucose (FPG) between biopsies (per 10 mg/dL increase; odds ratio [OR] [95% confidence interval; CI] = 1.4 [1.04-1.8]; P = 0.024) and cumulative use of dideoxynucleoside analogs (per year; OR [95% CI] = 1.5 [1.2-1.8]; P = 0.001). Persistent steatohepatitis or progression to steatohepatitis between biopsies was observed in 27 (18%) patients. Persistence of or progression to steatohepatitis was associated with progression ≥ 1 fibrosis stages between biopsies (OR [95% CI] = 2.4 [1.01-5.7]; P = 0.047). CONCLUSIONS: HS progresses frequently and regression is rarely observed in HIV/HCV-coinfected patients, including in those on ART. Cumulative exposure to dideoxynucleoside analogs and increases in FPG are related with HS progression. Stetatohepatitis is frequently observed in these patients and is linked to fibrosis progression.
Assuntos
Coinfecção/virologia , Fígado Gorduroso/patologia , Infecções por HIV/patologia , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Adulto , Distribuição por Idade , Análise de Variância , Antivirais/uso terapêutico , Biópsia por Agulha , Estudos de Coortes , Coinfecção/epidemiologia , Coinfecção/patologia , Intervalos de Confiança , Progressão da Doença , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/virologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Humanos , Imuno-Histoquímica , Incidência , Testes de Função Hepática , Masculino , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não ParamétricasRESUMO
Objetivo El objetivo de este estudio fue evaluar si la determinación de RNA del virus de la hepatitis C (VHC-RNA) a las 12 semanas tras la finalización del tratamiento podía predecir la respuesta viral sostenida al tratamiento anti-VHC (interferón pegilado alfa-2a y ribavirina) en enfermos coinfectados por el virus de la inmunodeficiencia humana (VIH).Enfermos y métodos Fueron incluidos los pacientes coinfectados por VIH y VHC que completaron un curso completo de tratamiento anti-VHC y que fueron evaluados a las semanas +12 y +24 tras la finalización del tratamiento para determinación del HCV-RNA sérico (RealTime HCV (Abbott, Wiesbaden, Alemania) (límite inferior de detección, 12 U/ml).Resultados Cuarenta de los 66 enfermos tratados (61%) presentaron una respuesta al final del tratamiento. Se les realizó una valoración a las 12 y 24 semanas tras el fin de la terapia. El VHC-RNA sérico fue indetectable en 28 de ellos a la semana +12, y el 100% de ellos permaneció indetectable a la semana +24 (el patrón de referencia de respuesta viral sostenida). El valor predictivo positivo fue 100% (intervalo de confianza al 95% 98,21-100%).Conclusión La evaluación posterior al tratamiento de la hepatitis crónica C en enfermos coinfectados por VIH para detectar la presencia de recaída virológica puede ser realizada a la semana +12, en lugar de a la semana +24, proporcionando así una nueva definición de respuesta virológica sostenida (AU)
Objective The aim of this study was to assess whether measurement of hepatitis C virus RNA (HCV-RNA) at 12 weeks post-treatment could predict sustained virological response (SVR) to antiviral therapy for chronic hepatitis C (pegylated interferon alfa-2a and ribavirin) in HIV-co-infected patients. Patients and methods HIV-HCV co-infected patients were included if they completed a full course of anti-HCV therapy, achieved an end-of-treatment response and complied with the week +12 and +24 post-treatment follow-up schedule for serum HCV-RNA determination (Real-time HCV (Abbott, Wiesbaden, Germany) (lower limit of detection, 12 IU/ml).Results Forty out of 66 patients (61%) showed an end-of-treatment response. They were assessed in a follow-up visit at +12 and at +24 weeks post-treatment. Serum HCV-RNA was undetectable in 28 of them at +12 weeks, and 100% of these remained undetectable at 24 weeks post-treatment (the gold standard of (SVR). The positive predictive value was 100% (95% confidence interval, 98.21-100%).Conclusion Post-treatment follow-up to identify virological relapse could be shortened to 12 weeks, providing a new definition of sustained virological response (AU)
Assuntos
Humanos , RNA Viral/análise , Hepacivirus/patogenicidade , Hepatite C Crônica/microbiologia , Hepatite C Crônica/complicações , Infecções por HIV/complicações , Interferons/uso terapêutico , Carga Viral , Ribavirina/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to assess whether measurement of hepatitis C virus RNA (HCV-RNA) at 12 weeks post-treatment could predict sustained virological response (SVR) to antiviral therapy for chronic hepatitis C (pegylated interferon alfa-2a and ribavirin) in HIV-co-infected patients. PATIENTS AND METHODS: HIV-HCV co-infected patients were included if they completed a full course of anti-HCV therapy, achieved an end-of-treatment response and complied with the week +12 and +24 post-treatment follow-up schedule for serum HCV-RNA determination (Real-time HCV (Abbott, Wiesbaden, Germany) (lower limit of detection, 12 IU/ml). RESULTS: Forty out of 66 patients (61%) showed an end-of-treatment response. They were assessed in a follow-up visit at +12 and at +24 weeks post-treatment. Serum HCV-RNA was undetectable in 28 of them at +12 weeks, and 100% of these remained undetectable at 24 weeks post-treatment (the gold standard of (SVR). The positive predictive value was 100% (95% confidence interval, 98.21-100%). CONCLUSION: Post-treatment follow-up to identify virological relapse could be shortened to 12 weeks, providing a new definition of sustained virological response.
Assuntos
Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Carga Viral , Adulto , Feminino , Infecções por HIV/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , RNA Viral/sangue , Fatores de TempoRESUMO
BACKGROUND AND AIMS: Analysis of the influence of the effects of increased intestinal permeability on haemodynamic alterations in human immunodeficiency virus (HIV)-infected patients with decompensated hepatitis C virus (HCV)-related liver disease. METHODS: Forty HIV/HCV co-infected patients and 40 HCV mono-infected patients, 20 of them with compensated cirrhosis and 20 with a previous decompensation, and 20 healthy controls, were studied. Intestinal permeability was determined by serum levels of lipopolysaccharide-binding protein (LBP). Monocyte expression of toll-like receptor 4 (TLR-4), serum levels of interleukin (IL)-6 and soluble receptors of tumour necrosis factor (sTNFRI) were analysed. Cardiac index, systemic vascular resistance (SVR), plasma renin activity (PRA) and aldosterone concentration were also determined in cirrhotic patients. RESULTS: Serum levels of LBP, TLR-4, IL-6 and sTNFRI were significantly higher in HIV-HCV co-infected and HCV mono-infected patients with decompensated cirrhosis compared with those with compensated liver disease. Significantly lower values of SVR and higher values of cardiac index, PRA and aldosterone concentration were observed in patients with decompensated cirrhosis compared with those with compensated liver disease, particularly in those with elevated levels of IL-6. There were no significant differences between HIV/HCV co-infected and HCV mono-infected patients. CONCLUSIONS: Higher intestinal permeability and consequent macrophage activation is observed in patients with cirrhosis; this permeability is even higher in those with portal hypertension. Serum values of IL-6 are associated with the characteristic haemodynamic derangement observed in advanced phases of cirrhosis. HIV/HCV co-infected cirrhotic patients present inflammatory and systemic haemodynamic alterations similar to those observed in HCV mono-infected patients.
Assuntos
Translocação Bacteriana , Infecções por HIV/fisiopatologia , Hemodinâmica , Hepatite C/fisiopatologia , Intestinos/microbiologia , Cirrose Hepática/fisiopatologia , Proteínas de Fase Aguda , Adulto , Idoso , Aldosterona/sangue , Análise de Variância , Proteínas de Transporte/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Endotoxemia/imunologia , Endotoxemia/microbiologia , Endotoxemia/fisiopatologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Hepatite C/complicações , Hepatite C/imunologia , Hepatite C/microbiologia , Humanos , Hipertensão Portal/imunologia , Hipertensão Portal/microbiologia , Hipertensão Portal/fisiopatologia , Hipertensão Portal/virologia , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Cirrose Hepática/imunologia , Cirrose Hepática/microbiologia , Cirrose Hepática/virologia , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Monócitos/imunologia , Permeabilidade , Receptores do Fator de Necrose Tumoral/sangue , Renina/sangue , Sistema Renina-Angiotensina , Espanha , Receptor 4 Toll-Like/sangue , Resistência VascularRESUMO
OBJECTIVE: To provide information about the incidence and predictors of liver decompensation and death due to liver failure in human immunodeficiency virus (HIV)-infected patients with compensated hepatitis C virus (HCV)-related cirrhosis. METHODS: Prospective cohort study of 154 HIV-HCV-coinfected patients with a new diagnosis of Child-Pugh-Turcotte (CPT) class A compensated cirrhosis. We evaluated time from diagnosis to the first liver decompensation and death from liver disease, as well as predictors of these outcomes. RESULTS: Thirty-six patients (23.4%) developed liver decompensation. The incidence of liver decompensation was 6.40 cases per 100 person-years (95% confidence interval [CI], 4.18-9.38 cases per 100 person-years). Factors independently associated with liver decompensation were lack of HCV therapy (hazard ratio [HR], 3.38; 95% CI, 1.09-10.53; P = .035), baseline CD4 cell counts Assuntos
Infecções por HIV/complicações
, Hepatite C Crônica/complicações
, Cirrose Hepática/epidemiologia
, Cirrose Hepática/patologia
, Adulto
, Estudos de Coortes
, Feminino
, Humanos
, Incidência
, Cirrose Hepática/virologia
, Falência Hepática/epidemiologia
, Falência Hepática/mortalidade
, Masculino
, Prognóstico
, Estudos Prospectivos
, Fatores de Tempo
RESUMO
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.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Estudos de Coortes , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/efeitos adversos , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: To investigate whether concomitant antiretroviral therapy (ART) is a predictor of sustained virological response (SVR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with pegylated interferon plus ribavirin. METHODS: Three hundred and ten HIV/HCV-coinfected patients on pegylated interferon plus ribavirin treatment, 258 of them with concurrent ART, were included in this retrospective multicentre study. The predictors of SVR were evaluated. RESULTS: SVR was shown by 114 (37%) subjects. HCV genotype 2 or 3, plasma HCV-RNA load lower than 600 000 IU/mL, an exposure to the therapy against HCV infection > or =80% of the planned dose and baseline CD4 cell counts higher than or equal to 300/mm(3) were predictors of SVR. Likewise, patients without ART and those receiving a combination including tenofovir or stavudine plus lamivudine plus a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) showed a higher SVR rate than the subjects who were on other ART strategies at baseline [44%, 44% and 29%, respectively; adjusted odd ratio (95% CI) for no ART = 1.96 (1.07-4.76), P = 0.025, and for ART including tenofovir or stavudine plus lamivudine plus a PI or a NNRTI = 2.08 (1.16-3.70), P = 0.014]. CONCLUSIONS: The ART strategy on starting therapy with pegylated interferon plus ribavirin is a predictor of SVR in HIV/HCV-coinfected patients. Subjects without ART and those receiving combinations of a PI or a NNRTI with a nucleos(t)ide backbone of tenofovir or stavudine plus lamivudine respond better than those who receive other regimens.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/complicações , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C/complicações , Hepatite C/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Polietilenoglicóis/administração & dosagem , RNA Viral/sangue , Proteínas Recombinantes , Resultado do TratamentoRESUMO
OBJECTIVE: To define the course of HIV-HCV-coinfected patients with compensated and decompensated liver cirrhosis and to investigate the survival and the risk factors for death. PATIENTS AND METHODS: Ninety-two HIV-infected patients with HCV-related cirrhosis (50 of them without and 42 with previous decompensations) were prospectively followed up during a median period of 20 months. Clinical, biochemical, virological and immunological factors were analysed. Multivariate analyses were performed of those factors associated with decompensations and mortality. RESULTS: There were 168 readmissions due to liver-disease-related causes. A Child-Pugh index > or =6 in those without previous decompensations (hazard ratio [HR] 7.94, 95% confidence interval [CI] 1.59-39.58; P = 0.014), and Child-Pugh index > or =9 (HR 2.68, 95% CI 1.13-6.33; P = 0.003) and absence of HAART (HR 0.44, 95% CI 0.19-0.98; P = 0.048) in those with previous decompensations were independently associated with decompensation during the follow up. There were 27 deaths, 22 of them attributable to liver disease. Independent factors associated with liver-related mortality were a Child-Pugh index > or =9 (HR 6.24, 95% CI 2.31-16.85; P < 0.001), progression of Child-Pugh index during the follow up (HR 4.27, 95% CI 1.54-11.80; P = 0.008), more than one decompensation (HR 24.25, 95% CI 7.27-40.45; P < 0.001) and absence of HAART (HR 0.35, 95% CI 0.12-0.98; P = 0.002). CONCLUSIONS: Evolution from compensated to decompensated cirrhosis and death is influenced by markers of liver function and the absence of HAART. The importance of this last element must be adequately stressed.
Assuntos
Infecções por HIV/complicações , Hepatite C/complicações , Cirrose Hepática/complicações , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Antivirais/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Feminino , HIV/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Humanos , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Masculino , Estudos Prospectivos , Fatores de Risco , Carga ViralRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepacivirus/fisiologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , RNA Viral/sangue , Ribavirina/uso terapêutico , Adulto , Antivirais/administração & dosagem , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Polietilenoglicóis , Valor Preditivo dos Testes , Proteínas Recombinantes , Ribavirina/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Antivirais/efeitos adversos , Infecções por HIV/complicações , HIV , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Adulto , Anemia/sangue , Anemia/induzido quimicamente , Antivirais/administração & dosagem , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Fibrose , Infecções por HIV/tratamento farmacológico , Humanos , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Contagem de Leucócitos , Masculino , Neutropenia/sangue , Neutropenia/induzido quimicamente , Contagem de Plaquetas , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes , Estudos Retrospectivos , Ribavirina/administração & dosagem , Fatores de Risco , Espanha , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Zidovudina/uso terapêuticoRESUMO
OBJECTIVES: To determine the incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients with known stage of liver fibrosis. METHODS: All HIV/HCV-coinfected patients were monitored for a period of 12 months after starting nelfinavir-containing regimens and, with an available liver biopsy, were included in a retrospective study. RESULTS: A total of 82 patients were included in the study. Nine (10.9%) HIV/HCV-coinfected patients showed an episode of severe hepatotoxicity during the study period. Eight (9.8%) individuals showed grade 3 or 4 change in levels of serum alanine aminotransferase and one subject presented with an event of decompensated liver cirrhosis. Six (18.2%) of 33 patients with advanced liver fibrosis and three (6%) of 49 individuals without advanced liver fibrosis showed an episode of severe hepatotoxicity (P = 0.1). In the multivariate analysis, only nevirapine use during nelfinavir therapy [adjusted odds ratio (AOR) 8.9; 95% confidence interval (CI), 1.4-54.1; P = 0.01] was independently associated with risk of development of severe liver toxicity. CONCLUSIONS: The incidence of severe hepatotoxicity of nelfinavir-containing regimens is low among HIV/HCV-coinfected patients with known stage of liver fibrosis. In addition, our findings show that concomitant nevirapine use is associated with an increased risk of severe hepatotoxicity in these subjects. Likewise, the proportion of severe liver toxicity tended to be higher in individuals with advanced liver fibrosis.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Nelfinavir/efeitos adversos , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
We compared the incidence of and factors associated with hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%) HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001) patients in the former and in the latter group, respectively, showed HCC. Fifty-four (11%) patients without HCC at baseline developed such a disease during follow-up. There were no incident cases among the HIV-coinfected population. The density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95% IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5 (1.1-5)] were the only two independent predictors of the emergence of HCC. In the group of patients in whom the date of HCV infection could be estimated, the time elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The incidence of HCC in patients with HCV-related cirrhosis after the first hepatic decompensation is lower in HIV-coinfected patients. This is probably due to the fact that HIV infection shortens the survival of HCV-coinfected patients with end-stage liver disease to such an extent that HCC not had a chance to emerge.
Assuntos
Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologiaRESUMO
Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection < 23years (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [95% CI] = 0.3-0.9, P = 0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR = 0.5, 95% CI = 0.3-0.9, P = 0.01) were negatively associated with advanced fibrosis (> or = F3). PI-based HAART versus no use of HAART (AOR = 0.4, 95% CI = 0.2-0.7, P = 0.001) was negatively associated with fibrosis progression rate > or = 0.2 units/year and independently of age at HCV infection and CD4+ T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed > or = F3, compared with 65 (37%) patients without HAART (P = 0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed > or = F3 (P = 0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.