RESUMO
PURPOSE: With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome. METHODS: 303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30). RESULTS: All patients were male, median age was 39 years. Main routes of transmission were MSM (95%) and IVDU (3%). 69% of patients were infected with HCV GT 1, 4.3% with GT 2, 10.6% with GT 3, 16.1% with GT 4. Overall SVR rate was 69.3% (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94% vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR. CONCLUSIONS: Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.
Assuntos
Antivirais/administração & dosagem , Coinfecção/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Adulto , Quimioterapia Combinada/métodos , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: About one third of patients infected with human immunodeficiency virus (HIV) also have chronic hepatitis due to hepatitis C virus (HCV). HCV therapy with simeprevir, pegylated interferon alfa (PegIFNα) and ribavirin (RBV) have been shown to be superior to PegIFNα + RBV alone in non-HIV patients, but no randomized trials in patients with HCV genotype 1 (HCV-1)/HIV coinfection are available. METHODS: This was a historical comparison of study C212 (simeprevir + PegIFNα-2a + RBV in patients with HCV-1/HIV coinfection) with studies in which HCV-1/HIV coinfected patients were treated with PegIFNα-2a + RBV alone. A systematic literature search was performed to identify eligible studies. Efficacy and safety results of PegIFNα-2a + RBV studies were combined in random- and fixed-effects inverse-variance weighted meta-analyses of proportions using the Freeman-Tukey double arcsin transformation method, and compared with the results of study C212. RESULTS: The literature search revealed a total of 2392 records, with 206 articles selected for full-text review. Finally, 11 relevant articles reporting on 12 relevant study groups were included. Results on sustained virologic response 24 weeks after end of treatment (SVR24) were available from all 12 study groups. Pooled SVR24 for PegIFNα-2a + RBV from the random-effects meta-analysis was 28.2% (95% CI 23.8% to 32.9%). The comparison between study C212 (SVR24 = 72.6%; 95% CI 63.1% to 80.9%) revealed substantial superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV alone, with an absolute risk difference of 45% (95% CI 34 to 55). This finding was robust in a sensitivity analysis that only included historical studies with a planned treatment duration of at least 48 weeks and the same RBV dose as in study C212. No increases in the frequency of important adverse event categories including anemia were identified, but these analyses were limited by the low number of studies. CONCLUSION: This historical comparison provides first systematic evidence for the superiority of simeprevir + PegIFNα-2a + RBV compared to PegIFNα-2a + RBV in patients with HCV-1/HIV coinfection. Given the limitations of the historical comparison for safety endpoints, additional data on the comparative safety of simeprevir in patients with HCV-1/HIV coinfection would be desirable. TRIAL REGISTRATION: Identifier for study TMC435-TiDP16-C212 (ClinicalTrials.gov): NCT01479868.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Coinfecção/tratamento farmacológico , Quimioterapia Combinada , Genótipo , Infecções por HIV/complicações , HIV-1/genética , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in HIV/HCV co-infected patients in a large European cohort collaboration, including data from different European countries. METHODS: HIV/HCV co-infected patients were included if they were aged ≥16 years, received pegIFN alfa-2a or 2b and RBV combination treatment and were enrolled in the COHERE cohort collaboration. Logistic regression was used to evaluate the impact of abacavir on achieving a sustained virologic response (SVR) to HCV treatment. RESULTS: In total 1309 HIV/HCV co-infected patients who had received HCV therapy were included, of whom 490 (37 %) had achieved an SVR. No statistically significant difference was seen for patients using ABC-containing regimens compared to patients using an emtricitabine + tenofovir (FTC + TDF)-containing backbone, which was the most frequently used backbone. In the multivariate analyses, patients using a protease inhibitor (PI)-boosted regimen were less likely to achieve an SVR compared to patients using a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen (OR: 0.61, 95 % CI: 0.41-0.91). The backbone combinations zidovudine&lamivudine (AZT + 3TC) and stavudine&lamivudine (d4t + 3TC) were associated with lower SRV rates (0.45 (0.24-0.82) and 0.46 (0.22-0.96), respectively). CONCLUSION: The results of this large European cohort study validate that SVR rates are generally not affected by ABC. Use of d4T or AZT as part of the HIV treatment regimen was associated with a lower likelihood of achieving an SVR.
Assuntos
Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Coinfecção/tratamento farmacológico , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Europa (Continente) , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Humanos , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Ribavirina/uso terapêutico , Tenofovir/uso terapêutico , Zidovudina/uso terapêuticoRESUMO
BACKGROUND: Simeprevir is an oral, once-daily, hepatitis C virus (HCV) NS3/4A protease inhibitor for the treatment of chronic HCV genotype 1 infection. Human immunodeficiency virus (HIV) coinfection accelerates progression of liver disease. This uncontrolled, open-label trial explored the safety and efficacy of simeprevir in patients with HCV genotype 1/HIV type 1 (HIV-1) coinfection. METHODS: Patients received simeprevir (150 mg once daily) with pegylated interferon alfa-2a/ribavirin (peg-IFN/RBV) for 12 weeks. Noncirrhotic HCV treatment-naive patients and prior relapsers received response-guided therapy (RGT) with peg-IFN/RBV for 24 or 48 weeks. Prior null responders, prior partial responders, and patients with cirrhosis received peg-IFN/RBV for 48 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: One hundred and six patients (93 on antiretroviral therapy) were enrolled and treated. SVR12 rates were 79.2% in HCV treatment-naive patients, 57.1% in prior null responders, 86.7% in prior relapsers, and 70.0% in prior partial responders. Fifty-four of 61 eligible patients (88.5%) met RGT criteria for 24 weeks of peg-IFN/RBV, of whom 87.0% (47/54) achieved SVR12. SVR12 rates were 80.0% (36/45) and 63.6% (14/22) for patients with METAVIR scores of F0-F2 and F3-F4, respectively. Common adverse event (AE) rates were consistent with peg-IFN/RBV therapy (fatigue, headache, nausea, neutropenia). Most AEs were grade 1/2; serious AEs occurred in 5.7% of patients, none of which were fatal. CONCLUSIONS: Simeprevir was generally well tolerated with safety similar to that observed in HCV-monoinfected patients and high SVR12 rates in HCV treatment-naive patients, prior relapsers, prior partial responders, and prior null responders with HIV-1 coinfection. CLINICAL TRIALS REGISTRATION: NCT01479868.
Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Sulfonamidas/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Feminino , Infecções por HIV/virologia , Hepatite C Crônica/virologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Simeprevir , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Telaprevir (TVR) plus peginterferon-α2a (PEG-IFN-α2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN-α2a-ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown. OBJECTIVE: To assess the safety and efficacy of TVR plus PEG-IFN-α2a-ribavirin in patients with genotype 1 HCV and HIV-1 and to evaluate pharmacokinetics of TVR and antiretrovirals during coadministration. DESIGN: Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853). SETTING: 16 international multicenter sites. PATIENTS: 62 patients with HCV genotype 1 and HIV-1 who were HCV treatment-naive and receiving 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-α2a-ribavirin or placebo plus PEG-IFN-α2a-ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-α2a-ribavirin. MEASUREMENTS: HCV RNA concentrations. RESULTS: Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-α2a-ribavirin during the first 12 weeks. During this period, serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-α2a-ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a-ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a-ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a-ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a-ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had on-treatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR. LIMITATION: Small sample size and appreciable dropout rate. CONCLUSION: In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a-ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a-ribavirin.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Adulto , Fármacos Anti-HIV/uso terapêutico , Antivirais/efeitos adversos , Antivirais/farmacocinética , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Genótipo , HIV-1 , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/farmacocinética , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/efeitos adversos , Oligopeptídeos/farmacocinética , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Ribavirina/farmacocinética , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
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.
Assuntos
Algoritmos , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucinas/genética , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Ribavirina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Comorbidade , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Humanos , Interferon alfa-2 , Interferons , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Análise de Regressão , Estudos Retrospectivos , Resultado do Tratamento , Carga ViralRESUMO
PURPOSE: The relationship between peginterferon/ribavirin exposure and the probability of achieving a sustained virologic response (SVR) in HIV-HCV coinfected patients is not well described. We conducted a retrospective analysis of HIV-HCV coinfected patients randomized to 48 weeks of treatment with peginterferon alfa-2a (40 kD) 180 µg/week and ribavirin 800 mg/day in the multinational APRICOT study to define optimal exposure thresholds. METHOD: Actual drug exposure was estimated in 287 patients, taking into consideration dose reductions for adverse events or laboratory abnormalities. RESULTS: SVR overall and SVR in those completing treatment was, respectively, 29% and 37% among HCV genotype-1 patients and 59% and 68% among genotype non-1 patients. No patients with ≤40% exposure to ribavirin achieved an SVR. Receiver operating characteristic analysis identified that threshold exposures to both drugs of >75% (genotype-1) and >60% (genotype non-1) are associated with SVR. An existing generalized additive model populated with data from HCV monoinfected patients was updated to predict an overall SVR of 37% if genotype-1 patients received ribavirin 1000 or 1200 mg/day but at the cost of a higher incidence of anemia (23%). CONCLUSION: Completion of scheduled treatment and exceeding certain thresholds for exposure to peginterferon alfa 2a (40 kD) and ribavirin is associated with higher SVR rates.
Assuntos
Antivirais/administração & dosagem , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/virologia , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes/administração & dosagem , Estudos RetrospectivosRESUMO
Direct-acting antivirals (DAAs) have tremendously improved the treatment of hepatitis C virus (HCV) infections also in human immunodeficiency virus (HIV)-positive individuals. Curing HCV infection is of particular importance in HIV-positive individuals as liver disease progression is accelerated in the course of concomitant HIV infection. Former challenges, such as safety and tolerability as well as reduced treatment uptake of pegylated interferon and ribavirin-based treatments, have been overcome with the approval of DAAs. Indeed, rates of discontinuation under modern all-oral DAA therapy in HIV/HCV coinfection have been reported to be <1%. Rates of sustained virological response (SVR) following treatment have aligned with those seen in HCV monoinfected patients, resulting in an equalisation of treatment recommendations for HCV monoinfected and HIV/HCV coinfected patients. Nevertheless, coinfection with HIV has been associated with slightly higher relapse rates in some real-world cohorts, arousing discussion regarding more individualised treatment once again. Moreover, an ongoing epidemic of acute HCV infections in HIV-positive men who have sex with men with high re-infection rates challenges physicians and researchers. The present review gives a concise summary of the remaining challenges in HCV treatment of HIV-positive individuals.
Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/patologia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/métodos , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Coinfecção/virologia , Interações Medicamentosas , Quimioterapia Combinada , Fluorenos/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Minorias Sexuais e de Gênero/estatística & dados numéricos , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Resultado do TratamentoAssuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: According to guidelines all HIV-HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV-HBV patients in the EuroSIDA study. METHODS: All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events. RESULTS: 953 HIV-HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4+ T-cell count <350 cells/mm3 decreased from 85% to 52% in the periods 2002-2006 to 2007-2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events (n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir. CONCLUSIONS: Although use of tenofovir-based cART among HIV-HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.
Assuntos
Antirretrovirais/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Coinfecção , DNA Viral/antagonistas & inibidores , DNA Viral/biossíntese , DNA Viral/genética , Farmacorresistência Viral/efeitos dos fármacos , Europa (Continente) , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , HIV/efeitos dos fármacos , HIV/genética , HIV/metabolismo , Infecções por HIV/virologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/virologia , Humanos , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Organofosfonatos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Proteínas Recombinantes/uso terapêuticoRESUMO
Recurrent hepatitis C is a major cause of mortality in HIV/hepatitis C virus (HCV)-co-infected patients after orthotopic liver transplantation. We report sustained viral clearance in all four transplanted HIV/HCV-positive patients treated with pegylated interferon/ribavirin. Early therapy after HCV recurrence, tailoring treatment duration to the individual decline in HCV-RNA and the management of side effects are key factors for improved efficacy. At experienced centres interferon treatment is a valuable option for recurrent hepatitis C in HIV-positive patients.
Assuntos
Antivirais/administração & dosagem , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Transplante de Fígado , Administração Oral , Estudos de Coortes , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/cirurgia , Humanos , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , RNA Viral/análise , Proteínas Recombinantes , Recidiva , Ribavirina/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV. METHODS: A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 microg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin. Patients were treated for 48 weeks and followed for an additional 24 weeks. The primary end point was a sustained virologic response (defined as a serum HCV RNA level below 50 IU per milliliter at the end of follow-up, at week 72). RESULTS: The overall rate of sustained virologic response was significantly higher among the recipients of peginterferon alfa-2a plus ribavirin than among those assigned to interferon alfa-2a plus ribavirin (40 percent vs. 12 percent, P<0.001), or peginterferon alfa-2a plus placebo (40 percent vs. 20 percent, P<0.001). Among patients infected with HCV genotype 1, the rates of sustained virologic response were 29 percent with peginterferon alfa-2a plus ribavirin, 14 percent with peginterferon alfa-2a plus placebo, and 7 percent with interferon alfa-2a plus ribavirin. The corresponding rates among patients infected with HCV genotype 2 or 3 were 62 percent, 36 percent, and 20 percent. Neutropenia and thrombocytopenia were more common among patients treated with regimens that contained peginterferon alfa-2a, and anemia was more common among patients treated with regimens containing ribavirin. CONCLUSIONS: Among patients infected with both HIV and HCV, the combination of peginterferon alfa-2a plus ribavirin was significantly more effective than either interferon alfa-2a plus ribavirin or peginterferon alfa-2a monotherapy.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa , Interferon-alfa/uso terapêutico , Polietilenoglicóis , Ribavirina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/complicações , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/efeitos adversosRESUMO
BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 µg, for 24 weeks. If required by RGT, PegIFN/RBV without DCV was extended for an additional 24 weeks of therapy. The primary endpoint was the proportion of patients with sustained virologic response at post-treatment Week 12 (SVR12). RESULTS: Overall, 224 (74%) patients achieved SVR12 and the lower bound of the 95% confidence interval was higher than the historic SVR rate with PegIFN/RBV alone (70 vs. 29%). Most common adverse events (AEs) were fatigue, neutropenia, anemia, asthenia and headache. On-treatment serious AEs occurred in 24/301 (8%) patients; 18/301 (6%) discontinued treatment due to AE. CONCLUSIONS: DCV + PegIFN/RBV led to sustained HCV virologic response in the majority of HIV-1-HCV-coinfected patients, regardless of concomitant ART. HIV control was not compromised and no new safety signals were identified. This study supports DCV use in HIV-1-HCV-coinfected patients, while allowing the vast majority of patients to remain on their existing ART regimen.
Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Imidazóis/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos , Coinfecção/virologia , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Pirrolidinas , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/administração & dosagem , Resultado do Tratamento , Valina/análogos & derivados , Adulto JovemRESUMO
BACKGROUND: Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic. METHODS: Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of hepatitis C infection with pegylated interferon (peg-IFN) therapy. RESULTS: Early treatment resulted in sustained virological response in 61% of patients. Peg-IFN alone showed similar treatment response rates and lower incidence of anaemia compared with peg-IFN+ribavirin combination therapy. Higher treatment response rates were observed in patients treated over 48 weeks compared with 24 weeks. CONCLUSIONS: Treatment of hepatitis C in HIV-positive individuals in the acute phase of infection leads to high rates of sustained virological response. Optimal time and mode of therapy have yet to be defined.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Hepatite C/etiologia , Hepatite C/transmissão , Humanos , Interferon alfa-2 , Masculino , Proteínas Recombinantes , Doenças Virais Sexualmente Transmissíveis/tratamento farmacológico , Doenças Virais Sexualmente Transmissíveis/etiologia , Doenças Virais Sexualmente Transmissíveis/transmissãoRESUMO
OBJECTIVE: Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. STARTVerso4 assessed the efficacy and safety of faldaprevir and response-guided pegylated interferon α-2a/ribavirin (PegIFN/RBV) in individuals with HCV/HIV co-infection. DESIGN: A phase 3 open-label study (NCT01399619). METHODS: Individuals (Nâ=â308) co-infected with HCV genotype 1 (treatment-naive or prior interferon relapsers) and HIV [96% on antiretroviral therapy (ART)] received faldaprevir 120âmg (Nâ=â123) or 240âmg (Nâ=â185) and PegIFN/RBV. Those receiving a protease inhibitor or efavirenz ART were assigned to faldaprevir 120 or 240âmg, respectively. Individuals achieving early treatment success (ETS; HCV RNA <25âIU/ml at week 4 and undetectable at week 8) were randomized to 24 or 48 weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: SVR12 was achieved in 221 (72%) individuals, and the rates were comparable across faldaprevir doses. ETS was achieved in 80%, and of these 86% achieved SVR12, with comparable rates with 24 and 48 weeks of PegIFN/RBV (87 and 94%, respectively). In multivariate analysis, age below 40 years, IL28B CC genotype, and baseline HCV RNA below 800â000âIU/ml were associated with SVR12 (Pâ=â0.027, Pâ<â0.0001, and Pâ=â0.0002, respectively), whereas treatment (ART regimen and faldaprevir dose), liver cirrhosis, and genotype 1 subtype were not. The safety profile was comparable to that of faldaprevir in HCV-monoinfected individuals. CONCLUSIONS: High SVR12 rates were achieved with faldaprevir and PegIFN/RBV in HIV/HCV co-infected individuals, regardless of faldaprevir dose and background ART, HCV genotype 1 subtype, or cirrhosis status. SVR rates mirrored those obtained with similar regimens in HCV monoinfected individuals.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Tiazóis/uso terapêutico , Adolescente , Adulto , Idoso , Ácidos Aminoisobutíricos , Antirretrovirais/uso terapêutico , Quimioterapia Combinada/métodos , Humanos , Leucina/análogos & derivados , Pessoa de Meia-Idade , Prolina/análogos & derivados , Quinolinas , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Carga Viral , Viremia/diagnóstico , Adulto JovemRESUMO
BACKGROUND: IL28B genotype predicts response to treatment against HCV with pegylated interferon/ribavirin (PR) and impacts on the outcome of therapy including telaprevir (TVR). This study aimed to determine the influence of the favourable IL28B genotype on early viral kinetics during therapy with TVR/PR in HIV-HCV-coinfected patients. METHODS: All HIV-HCV genotype 1 coinfected subjects who received TVR/PR for at least 4 weeks were included from populations prospectively followed in 22 centres throughout Germany, Switzerland and Spain. RESULTS: Of the 129 subjects included, 38 (29.5%) presented with IL28B genotype CC and 94 (72.9%) were treatment-experienced. A total of 96 (73.8%) patients showed undetectable plasma HCV RNA at treatment week (W)4: 30 (78.9%) of the IL28B-CC carriers and 65 (71.4%) of the non-CC carriers (P=0.377). Among treatment-naive patients, proportions of undetectable HCV RNA among IL28B-CC versus non-CC carriers were 8/9 (88.9%) versus 3/9 (33.3%; P=0.016) and 14/17 (82.4%) versus 11/18 (61.1%; P=0.164) at W2 and W4. The decrease of HCV RNA at W2 and W4 was similar among the IL28B carriers. CONCLUSIONS: IL28B genotype does not predict W4 response to TVR/PR in HIV-HCV-coinfected patients, regardless of their treatment history. However, there is evidence of an impact on response during the first weeks in treatment-naive patients.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Interleucinas/genética , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Coinfecção , Feminino , Expressão Gênica , Genótipo , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/genética , Hepatite C/virologia , Humanos , Interferons , Masculino , RNA Viral/antagonistas & inibidores , RNA Viral/genética , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Antivirais/uso terapêutico , Infecções por HIV/epidemiologia , Hepatite C/tratamento farmacológico , Doença Aguda , Contagem de Linfócito CD4 , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C/transmissão , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , RNA Viral/análise , Proteínas Recombinantes , Ribavirina/uso terapêutico , Fatores de RiscoRESUMO
BACKGROUND: The aim of this study was to evaluate strategies for assignment of HIV-HCV genotype-1-coinfected patients (HIV-HCV-GT1) to either dual-therapy or direct-acting antiviral agent (DAA)-based triple-therapy. METHODS: A total of 148 treatment-naive HIV-HCV-GT1 who received antiviral therapy with pegylated interferon/ribavirin were included in this multinational, retrospective analysis. Patients with rapid virological response (RVR) were treated for 48 weeks, while patients without RVR received either 48 or 72 weeks of treatment. IL28B rs12979860 (IL28B) non-C/C, advanced liver fibrosis and high HCV RNA were considered as established risk factors for treatment failure. RESULTS: A trend toward higher sustained virological response (SVR) rates in patients with IL28B C/C (65% [37/57] versus 51% [40/79]; P=0.097) was observed. Higher SVR rates were observed in patients without advanced liver fibrosis (61% [47/77] versus 42% [22/52]); P=0.036) and without high HCV RNA (73% [35/48] versus 49% [49/100]; P=0.006), as well as in patients with RVR (90% [35/39] versus 45% [49/109]; P<0.001). SVR rates varied statistically significantly between the risk factors for treatment failure subgroups (86% [6/7] versus 69% [34/49] versus 48% [21/44] versus 20% [4/20] for zero, one, two and three risk factors, respectively; P<0.001). In patients without RVR, higher rates of SVR were observed in those treated for 72 weeks (62% [23/37]), when compared to patients treated for 48 weeks (36% [26/72]; P=0.01). CONCLUSIONS: RVR had an excellent positive predictive value for the response to dual-therapy in HIV-HCV-GT1, emphasizing the utility of a lead-in phase for assigning these patients to dual-therapy or DAA-based triple-therapy. The use of an IL28B-guided approach was suboptimal, while a combination of established baseline predictors may provide guidance for individual treatment decisions prior to the initiation of antiviral therapy. However, the extension of treatment duration to 72 weeks in HIV-HCV-GT1 without RVR should be strongly considered if triple-therapy is not available.
Assuntos
Antivirais/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Hepatite C/complicações , Hepatite C/genética , Hepatite C/imunologia , Hepatite C/virologia , Humanos , Interferon-alfa/uso terapêutico , Interferons , Interleucinas/genética , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Early treatment of acute HCV infection has been shown to improve virological response rates in HIV-positive patients; however, details on when and how to best treat acute HCV infection remain unclear at present. METHODS: In this European multicentre cohort study, HIV-positive patients with acute HCV infection were offered immediate or delayed anti-HCV therapy, pegylated interferon or pegylated interferon plus ribavirin combination therapy for 24 or 48 weeks, depending on the local protocol. The main outcome measure was the rate of sustained virological response (SVR). RESULTS: A total of 150 HIV-infected men with acute HCV were enrolled between 2001 and 2006, 111 of whom received anti-HCV therapy. The predominant HCV genotype was type 1 and was present in 71 (64%) patients. Patients were treated with pegylated interferon (n=14) or pegylated interferon plus ribavirin (n=97), with a median duration of treatment of 25 weeks. SVR was obtained in 62% (95% confidence interval 52-71) of patients. There was no difference in SVR by genotype, CD4(+) T-cell count, HIV RNA, HCV RNA, alanine aminotransferase levels or use of ribavirin. Negative HCV RNA at weeks 4 and 12 were strong predictors of SVR. CONCLUSIONS: High rates of SVR (62%) were obtained in HIV-coinfected patients with acute HCV infection undergoing early anti-HCV treatment using pegylated interferon alone or in combination with ribavirin. Treatment response at weeks 4 and 12 might be of help to further guide treatment duration. Urgent prospective studies are needed to further determine the optimal treatment regimen and the duration of therapy.