RESUMO
BACKGROUND: Obesity among persons living with HIV (PLWH) has increased and weight gain after antiretroviral therapy (ART) can lead to metabolic disorders and impact survival. Our objective was to analyze weight and metabolic changes in HIV näive patients after 48 weeks of ART. METHODS: Observational, retrospective, multicentered cohort study comprising naïve-patients who started tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) or abacavir/lamivudine/dolutegravir (ABC/3TC/DTG), with no change in treatment for 48 weeks. Clinical and metabolic parameters were collected at baseline and week-48. Statistical program used was SPSS 21.0.0. RESULTS: The study included 329 participants from 6 hospitals. Participants were 89% male and 10% had AIDS diagnosis. Median age was 35 (IQR 27-43) years. Median baseline CD4 count was 417 (IQR 250-569) cell/mm3 and HIV viral load 4.65 (IQR 4.21-5.18) log10 copies/ml. Baseline median weight was 70 (IQR 62-79) kg, body mass index 23.4 (IQR 21.2-26.0) kg/m2; 22.7% overweight and 6.4% obese. ART regimens: ABC/3TC/DTG (196), TAF/FTC/EVG/c (133). Baseline characteristics were similar in both ART groups. Average weight gain at week-48 was 2.9 (SD 5.5) kg (p < 0.0001) with no differences between both groups. There was an increase in obesity (6.4%-8%; p < 0.003) and overweight (22.7%-28.9%; p < 0.0001). Weight increase was associated with AIDS: OR 3.05 (95%; CI 1.009-9.22), p = 0.048; and lower baseline weight: OR 1.032 (95% CI 1.009-1.05), p = 0.006. CONCLUSIONS: After ART initiation patients gain weight regardless of the regimen they take. Weight gain is associated with AIDS and the use of TAF/FTC/EVG/c.
Assuntos
Síndrome da Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , Humanos , Masculino , Adulto , Feminino , Lamivudina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Estudos Retrospectivos , Espanha/epidemiologia , Sobrepeso/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antirretrovirais/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Aumento de Peso , Obesidade/epidemiologiaRESUMO
AIM: We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain. MATERIAL AND METHODS: Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded. RESULTS: Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8-97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of -2.2% (90% CI, -4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin. CONCLUSIONS: Our results confirm that OBV/PTV/r ± DSV ± RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , 2-Naftilamina , Anilidas/efeitos adversos , Anilidas/uso terapêutico , Antivirais/efeitos adversos , Carbamatos/efeitos adversos , Carbamatos/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Seguimentos , HIV-1/genética , Humanos , Lactamas Macrocíclicas , Modelos Logísticos , Compostos Macrocíclicos/efeitos adversos , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prolina/análogos & derivados , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Espanha , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Resposta Viral Sustentada , Resultado do Tratamento , Uracila/efeitos adversos , Uracila/análogos & derivados , Uracila/uso terapêutico , ValinaRESUMO
Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be influenced by the presence of resistance-associated substitutions (RASs). This study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of sustained viral response (SVR) in naïve HCV-infected patients in clinical practice. All HCV-infected patients who initiated treatment with interferon (IFN)-free DAA-based regimens between March 2016 and May 2017 in 17 Spanish hospitals and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were included. Patients had to be DAA naïve, with the exception of sofosbuvir with/without IFN. In one hospital, participants received therapy guided by the presence of NS5A-RASs (RGT population). Patients enrolled in the remaining hospitals, without baseline RASs testing, constituted the control population. A total of 120 and 512 patients were included in the RGT and control populations, respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A-RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2% (three relapses) whereas it was 98.8% (six relapses) in the control population (p = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naïve HCV-infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy in clinical practice.
Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Antivirais/farmacologia , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada , Proteínas não Estruturais Virais/genéticaRESUMO
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.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Tiazóis/administração & dosagem , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Coinfecção/tratamento farmacológico , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrocompostos , Projetos Piloto , Polietilenoglicóis/efeitos adversos , RNA Viral/sangue , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Ribavirina/efeitos adversos , Tiazóis/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. METHODS: In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. RESULTS: Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. CONCLUSION: The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.
Assuntos
Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Prolina/análogos & derivados , Adulto , Coinfecção/tratamento farmacológico , Coinfecção/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Europa (Continente) , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prolina/administração & dosagem , Ribavirina/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the liver safety of raltegravir-including combinations in HIV/hepatitis C virus (HCV) co-infected patients. METHODS: Grade 3-4 transaminase elevations (TEs) and grade 4 total bilirubin elevations (TBEs) were assessed during 12 months in 108 HIV/HCV co-infected patients starting antiretroviral therapy including raltegravir in a retrospective cohort study. Furthermore, the relationship between baseline fibrosis and hepatotoxic events was determined. RESULTS: Eight patients (7.4%) developed grade 3 TEs and two (1.9%) patients showed grade 4 TEs. TBE grade 4 was detected in two (1.9%) patients. No patient permanently discontinued raltegravir because of hepatotoxic events. Of the patients with and without significant fibrosis, six (9.4%) and two (11.8%), respectively, showed grade 3-4 TEs (Pâ=â0.769). Grade 3-4 TEs was observed in four (9.8%) patients in whom cirrhosis was ruled out, while none of the patients diagnosed with cirrhosis developed grade 3-4 TEs (Pâ=â0.303). During the follow-up, the median (Q1-Q3) CD4 cell count increased from 257 (145-421) cells/mm(3) to 407 (213-587) cells/mm(3) (Pâ<â0.0001) and the number of patients with an undetectable HIV viral load augmented from 33 (30.6%) to 73 (81.1%) (Pâ=â0.002). CONCLUSIONS: Raltegravir-containing regimens are safe in HIV/HCV co-infected patients. The incidence of severe liver toxicity of raltegravir in these individuals is in the range of boosted protease inhibitors in clinical trials. The frequencies of grade 3-4 TEs and grade 4 TBEs were similar in patients receiving raltegravir with or without significant fibrosis or cirrhosis.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/patologia , Fígado/efeitos dos fármacos , Pirrolidinonas/efeitos adversos , Adulto , Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Bilirrubina/sangue , Estudos de Coortes , Feminino , Humanos , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Pirrolidinonas/administração & dosagem , Raltegravir Potássico , Estudos Retrospectivos , Transaminases/sangueRESUMO
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