RESUMEN
The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Oxazinas , Piperazinas , Piridonas , Humanos , Persona de Mediana Edad , Lamivudine/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , España , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Antirretrovirales/uso terapéutico , LípidosRESUMEN
Human leishmaniasis is a neglected tropical disease which affects nearly 1.5 million people every year, with Mexico being an important endemic region. One of the major defense mechanisms of these parasites is based in the polyamine metabolic pathway, as it provides the necessary compounds for its survival. Among the enzymes in this route, trypanothione reductase (TryR), an oxidoreductase enzyme, is crucial for the Leishmania genus' survival against oxidative stress. Thus, it poses as an attractive drug target, yet due to the size and features of its catalytic pocket, modeling techniques such as molecular docking focusing on that region is not convenient. Herein, we present a computational study using several structure-based approaches to assess the druggability of TryR from L. mexicana, the predominant Leishmania species in Mexico, beyond its catalytic site. Using this consensus methodology, three relevant pockets were found, of which the one we call σ-site promises to be the most favorable one. These findings may help the design of new drugs of trypanothione-related diseases.
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Antiprotozoarios , Leishmania , Leishmaniasis , Humanos , Simulación del Acoplamiento Molecular , Leishmania/metabolismo , NADH NADPH Oxidorreductasas/metabolismo , Leishmaniasis/parasitología , Antiprotozoarios/uso terapéuticoRESUMEN
OBJECTIVES: HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials. METHODS: The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts. RESULTS: Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (Pâ=â1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use. CONCLUSIONS: G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Humanos , Antivirales/farmacología , Coinfección/tratamiento farmacológico , Coinfección/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Ensayos Clínicos como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Introduction: Introduction: malnutrition and sarcopenia are frequent in the population with liver cirrhosis and have a negative impact on the performance status and life expectancy of these patients. There are multiple assessment tools for malnutrition and sarcopenia in cirrhosis. Objective: to assess malnutrition and sarcopenia in liver cirrhosis and to compare the accuracy of diagnostic tools in this population. Method: a cross-sectional analytical study was conducted with convenience sampling by using continuous inclusion of patients with liver cirrhosis in a tertiary care center during December 2018 to May 2019. The nutritional assessment was carried out with arm anthropometry, body mass index (BMI), and the algorithm of the Royal Free Hospital Subjective Global Assessment (RFH-SGA). For the evaluation of sarcopenia, the hand grip strength test with a hand dynamometer was applied. The results were reported in measures of central tendency expressed in frequency and percentage. Results: a total of 103 patients were included with a predominance of the male gender (79.6 %) and a mean age of 51 years (± 10). The etiology of liver cirrhosis corresponded more frequently to alcohol consumption (68 %) and most of the patients were Child-Pugh C (57.3 %) with a mean MELD of 21.9 (± 8.9). A mean BMI with dry weight of 25.2 kg/m2 was reported, and with respect to the WHO classification by BMI, 7.8 % were underweight and 59.2 % were malnourished by RFH-SGA. Sarcopenia was present in 88.3 % using the hand grip strength test, for which a mean of 18.99 kg was found. A Kendall's Tau-b rank correlation coefficient was performed between BMI and RFH-SGA, which showed no statistically significant association, as well as between mean arm muscle circumference percentiles and hand grip strength. Conclusions: global assessment in liver cirrhosis should include screening for malnutrition and sarcopenia, for which validated, accessible and safe application tools should be used, such as anthropometric assessment, RFH-SGA, and hand grip strength.
Introducción: Introducción: la malnutrición y la sarcopenia son frecuentes en la población con cirrosis hepática y generan un impacto negativo en el estado funcional y la esperanza de vida de estos pacientes. Existen múltiples herramientas para la valoración de la malnutrición y la sarcopenia en los pacientes con cirrosis hepática. Objetivo: valorar la malnutrición y la sarcopenia en la cirrosis hepática y comparar distintas herramientas diagnósticas aplicables en esta población. Método: se realizó un estudio analítico de corte transversal con muestreo a conveniencia mediante inclusión continua de pacientes con cirrosis hepática en un hospital de tercer nivel durante diciembre de 2018 a mayo de 2019. Se realizó la valoración nutricional con la antropometría del brazo, el índice de masa corporal (IMC) y el algoritmo del Royal Free Hospital Subjetive Global Assessment (RFH-SGA). Para la valoración de la sarcopenia se aplicó la fuerza de agarre de la mano con un dinamómetro. Los resultados se reportaron en medidas de tendencia central expresadas en frecuencia y porcentaje. Resultados: se incluyeron un total de 103 pacientes, predominando el género masculino (79,6 %), con una edad media de 51 años. La etiología más frecuente de la cirrosis hepática fue el consumo de alcohol (68 %), predominando la clase Child-Pugh C (57,3 %) con una media de MELD de 21,9 (± 8,9). Se reportó una media de IMC con peso seco de 25,2 kg/m2 y, respecto a la clasificación de la OMS, un 7,8 % se encontraban en bajo peso y un 59,2 % en malnutrición según la RFH-SGA. Un 88,3 % presentó sarcopenia al utilizar la fuerza de agarre de la mano, cuyo valor medio fue de 18,99 kg. Se realizó una correlación con Tau b de Kendall entre IMC y RFH-SGA sin evidenciarse ninguna asociación significativa, al igual que entre los percentiles de la circunferencia muscular media de brazo (MAMC) y la fuerza de agarre de la mano. Conclusiones: la valoración integral de la cirrosis hepática debe incluir el escrutinio de la malnutrición y la sarcopenia, existiendo herramientas de fácil acceso y aplicación segura validadas en esta población, como la valoración antropométrica, el RFH-SGA y la fuerza de agarre de la mano.
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Desnutrición , Sarcopenia , Humanos , Masculino , Persona de Mediana Edad , Sarcopenia/diagnóstico , Sarcopenia/etiología , Sarcopenia/epidemiología , Estado Nutricional , Fuerza de la Mano , Estudios Transversales , Cirrosis Hepática/complicaciones , Desnutrición/diagnóstico , Desnutrición/epidemiología , Desnutrición/etiología , Evaluación NutricionalRESUMEN
OBJECTIVES: Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. METHODS: Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. RESULTS: Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09-0.99),p = 0.048]. CONCLUSIONS: Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.
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Hepacivirus , Hepatitis C , Ácidos Aminoisobutíricos , Antivirales/farmacología , Bencimidazoles , Ciclopropanos , Combinación de Medicamentos , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Estudios Prospectivos , Pirrolidinas , Quinoxalinas , Sulfonamidas , Resultado del TratamientoRESUMEN
Hepatitis C Virus (HCV) affects approximately 71 million people infected, with 1.75 million people being diagnosed each year, according to the World Health Organization (WHO) estimates. HCV infection leads to cirrhosis, hepatocellular carcinoma (HCC), liver failure and death.
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Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Carcinoma Hepatocelular/prevención & control , Hepacivirus , Hepatitis C/diagnóstico , Hepatitis C/terapia , Humanos , Neoplasias Hepáticas/prevención & control , Salud MentalRESUMEN
Early diagnosis and treatment of incident cases of hepatitis C virus (HCV) infection is fundamental to eliminate HCV in HIV-positive patients. From January 2016 to December 2019, we attended 40 episodes of acute HCV infection (AHC) in 35 subjects (9 reinfections) who were coinfected with HIV. The patients were treated with direct-acting antiviral agents (DAAs) in seven hospitals in Andalusia, Spain. All were men who have sex with men (MSM), mean age was 42.9 (±8.3) years and median time of HIV infection was 46.6 months (IQR: 20.4-67.2). All received antiretroviral therapy and had undetectable HIV viral load (except 2 with 65 and 68 copies/mL); median CD4 count was 632 cells/mm3 (IQR: 553-896). Over half (74.3%) also had another concomitant sexually transmitted infection, syphilis (48.6%) being the most common. AHC was asymptomatic in 32 cases (80%). Genotypic distribution was G1a 65%, G4 32.5% and G1b 3%. Median time to DAA was 6 weeks (IQR: 4.3-18.3) and median baseline HCV RNA was 6.1 Log (IQR: 5.6-6.5). DAA regimens were SOF/LDV (19 episodes), SOF/VEL (14), ELB/GZV (5) and GLP/PIB (2). All presented sustained viral response and none discontinued due to adverse effects. In conclusion, early treatment with DAA in AHC patients proved effective and safe. It could be an excellent strategy to eliminate HCV infection in HIV-coinfected MSM.
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Coinfección , Epidemias , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Minorías Sexuales y de Género , Adulto , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Homosexualidad Masculina , Humanos , MasculinoRESUMEN
OBJECTIVE: There is scarce available evidence on the distribution over time of liver complications emergence in hepatitis C virus (HCV)-infected patients who achieve sustained virological response (SVR) with direct-acting antiviral (DAA)-based therapy. Therefore, we aimed at describing the kinetics of liver-related events appearance in this setting. DESIGN: A multicentric prospective cohort study. METHODS: HCV-monoinfected and HIV/HCV-coinfected patients from GEHEP-011 cohort, whose inclusion criteria were had achieved SVR with DAA-based therapy; liver stiffness prior to starting treatment at least 9.5âkPa; and available liver stiffness measurement at SVR. SVR was considered as the baseline time-point. RESULTS: One thousand and thirty-five patients were included, 664 (64%) coinfected with HIV. Before DAA-based therapy, 63 (6.1%) individuals showed decompensated cirrhosis. After SVR, 51 (4.9%) patients developed liver complications. Median (Q1-Q3) time to the emergence of hepatic events was hepatic encephalopathy 11 (7-24) months, ascites 14 (6-29) months, hepatocellular carcinoma (HCC) 17 (11-42) months and portal hypertension gastrointestinal bleeding (PHGB) 28 (22-38) months (Pâ=â0.152). We define two profiles of liver complications: those emerging earlier (encephalopathy and ascites) and, those occurring continuously during the follow-up (HCC, PHGB) [median (Q1-Q3) time to emergence 12.7 (6.6-28.2) months vs. 25.4 (12.5-41.53) months, respectively (Pâ=â0.026)]. CONCLUSION: The vast majority of HCV-infected patients who develop liver complications after reaching SVR with DAA do it within 3 years after SVR time-point. Specifically, hepatic encephalopathy and ascites do not usually emerge after this period. Conversely, HCC and PHGB may occur in longer term. It is critical to identify patients at risk of developing hepatic events to continue performing surveillance for them.
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Carcinoma Hepatocelular , Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cinética , Cirrosis Hepática , Neoplasias Hepáticas/tratamiento farmacológico , Estudios ProspectivosRESUMEN
Elbasvir/grazoprevir (EBR/GZR) use in drug users on opiate agonist therapy (OAT) is supported by the C-EDGE Co-STAR trial. SVR rates in this study were within those found in the rest of patients included by the EBR/GZR development programme. In clinical practice, however, efficacy could theoretically be lower. Thus, we aimed at evaluating the SVR rates of EBR/GZR among people who injected drugs (PWID) with and without OAT in clinical practice. Patients starting EBR/GZR included in the HEPAVIR-DAA (NCT02057003), recruiting HIV/HCV-coinfected patients or the GEHEP-MONO (NCT02333292), including HCV-monoinfected individuals, prospective cohorts were analysed. Overall SVR12 (ITT), discontinuations due to adverse effects and drop-outs were evaluated. The same analysis was carried out for PWID with and without OAT. 336 patients had started EBR/GZR and reached the SVR12 evaluation date. 318 [95%, 95% confidence interval (95% CI): 92%-98%] patients achieved SVR12. SVR12 was 97% (95% CI: 93%-99%, n/N = 141/145) among people who never used injecting drugs, 94% (95% CI: 88%-97%, n/N = 117/125) among PWIDs without OAT and 91% (95% CI: 81%-97%, n/N = 60/66) among PWIDs with OAT (p = 0.134). Five (1.5%) patients showed relapses, and two (0.6%) individuals showed viral breakthrough. The SVR12 rate for recent drug users was 69% (n/N = 18/26) compared with 97% (n/N = 276/284) for individuals without recent drug use (in the prior year) (p < 0.001). Among recent drug users, three (12%) showed relapses, and five (19%) were lost-to-follow-up. The SVR rates achieved with EBR/GZR were high in real-world conditions of use. However, PWID with recent drug use reach suboptimal response rates with EBR/GZR.
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Hepatitis C , Preparaciones Farmacéuticas , Amidas , Analgésicos Opioides , Antivirales/efectos adversos , Benzofuranos , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Humanos , Imidazoles , Estudios Prospectivos , Quinoxalinas/efectos adversos , SulfonamidasRESUMEN
BACKGROUND: The aim of this study was to assess the impact of human immunodeficiency virus (HIV) infection on the risk of developing hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV) who achieve sustained virological response (SVR) with direct-acting antiviral (DAA). METHODS: Multisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: (1) SVR with DAA-based combination; (2) liver stiffness (LS) ≥9.5 kPa previous to treatment; (3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients. RESULTS: In total, 1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC (11 [3.0%]; HCV-monoinfected, 8[1.2%]; HIV/HCV-coinfected individuals; P = .013). In the multivariable analysis, HIV coinfection was associated with a lower adjusted risk of developing HCC (subhazard ratio [sHR] = 0.27, 95% confidence interval [CI]: .08-.90; P = .034). Predictors of HCC emergence were: HCV genotype 3 (sHR = 7.9, 95% CI: 2.5-24.9; P < .001), MELD score at SVR >10 (sHR = 1.37, 95% CI: 1.01-1.86; P = .043) and LS value at SVR (sHR = 1.03, 95% CI: 1.01-1.06, for 1 kPa increase; P = .011). Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC (powered HR = 0.33, 95% CI: .11-.85). CONCLUSIONS: Among HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.
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Carcinoma Hepatocelular , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/epidemiología , Estudios Prospectivos , Respuesta Virológica SostenidaRESUMEN
BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.
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Coinfección , Várices Esofágicas y Gástricas , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/etiología , Hemorragia Gastrointestinal/tratamiento farmacológico , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. METHODS: Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. RESULTS: Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. CONCLUSIONS: VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. LAY SUMMARY: The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).
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Antivirales , Carbamatos , Farmacorresistencia Viral Múltiple , Quimioterapia Combinada/métodos , Hepacivirus , Hepatitis C Crónica , Compuestos Heterocíclicos de 4 o más Anillos , Compuestos Macrocíclicos , Retratamiento , Sofosbuvir , Sulfonamidas , Antivirales/administración & dosificación , Antivirales/efectos adversos , Antivirales/clasificación , Antivirales/farmacocinética , Carbamatos/administración & dosificación , Carbamatos/efectos adversos , Combinación de Medicamentos , Farmacorresistencia Viral Múltiple/efectos de los fármacos , Farmacorresistencia Viral Múltiple/genética , Europa (Continente)/epidemiología , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversos , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Compuestos Macrocíclicos/administración & dosificación , Compuestos Macrocíclicos/efectos adversos , Masculino , Persona de Mediana Edad , Retratamiento/métodos , Retratamiento/estadística & datos numéricos , Sofosbuvir/administración & dosificación , Sofosbuvir/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Respuesta Virológica Sostenida , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015-2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling. METHODS: A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall. RESULTS: Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030. CONCLUSION: Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.
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Infecciones por VIH/patología , Hepatitis C/diagnóstico , Modelos Teóricos , Antivirales/uso terapéutico , Estudios de Cohortes , Coinfección/epidemiología , Coinfección/patología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Prevalencia , Estudios Prospectivos , España/epidemiología , Trastornos Relacionados con Sustancias/patología , Respuesta Virológica SostenidaRESUMEN
OBJECTIVES: To investigate resistance-associated substitutions (RASs) as well as retreatment efficacies in a large cohort of European patients with failure of glecaprevir/pibrentasvir. METHODS: Patients were identified from three European Resistance Reference centres in Spain, Italy and Germany. Sequencing of NS3, NS5A and NS5B was conducted and substitutions associated with resistance to direct antiviral agents were analysed. Clinical and virological parameters were documented retrospectively and retreatment efficacies were evaluated. RESULTS: We evaluated 90 glecaprevir/pibrentasvir failures [3a (n = 36), 1a (n = 23), 2a/2c (n = 20), 1b (n = 10) and 4d (n = 1)]. Ten patients were cirrhotic, two had previous exposure to PEG-interferon and seven were coinfected with HIV; 80 had been treated for 8 weeks. Overall, 31 patients (34.4%) failed glecaprevir/pibrentasvir without any NS3 or NS5A RASs, 62.4% (53/85) showed RASs in NS5A, 15.6% (13/83) in NS3 and 10% (9/90) in both NS5A and NS3. Infection with HCV genotypes 1a and 3a was associated with a higher prevalence of NS5A RASs. Patients harbouring two (n = 34) or more (n = 8) RASs in NS5A were frequent. Retreatment was initiated in 56 patients, almost all (n = 52) with sofosbuvir/velpatasvir/voxilaprevir. The overall sustained virological response rate was 97.8% in patients with end-of-follow-up data available. CONCLUSIONS: One-third of patients failed glecaprevir/pibrentasvir without resistance. RASs in NS5A were more prevalent than in NS3 and were frequently observed as dual and triple combination patterns, with a high impact on NS5A inhibitor activity, particularly in genotypes 1a and 3a. Retreatment of glecaprevir/pibrentasvir failures with sofosbuvir/velpatasvir/voxilaprevir achieved viral suppression across all genotypes.
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Farmacorresistencia Viral , Hepacivirus , Ácidos Aminoisobutíricos , Antivirales/farmacología , Antivirales/uso terapéutico , Bencimidazoles , Ciclopropanos , Genotipo , Alemania/epidemiología , Hepacivirus/genética , Humanos , Italia/epidemiología , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prevalencia , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas , Retratamiento , Estudios Retrospectivos , España , Sulfonamidas , Proteínas no Estructurales Virales/genéticaRESUMEN
BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (Pâ<â0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (Pâ=â0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (Pâ=â0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (Pâ=â0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; Pâ=â0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.
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Carcinoma Hepatocelular/mortalidad , Coinfección , Infecciones por VIH , Hepatitis C Crónica , Neoplasias Hepáticas/mortalidad , Estudios de Cohortes , Infecciones por VIH/complicaciones , Hepacivirus , Hepatitis C Crónica/complicaciones , Humanos , Neoplasias Hepáticas/virología , Tasa de SupervivenciaRESUMEN
RESUMEN Fundamento: el tratamiento ideal de la hernia inguinal en pacientes geriátricos siempre ha sido un reto. Objetivo: evaluar la eficacia de la técnica de Halsted II en pacientes geriátricos con hernia inguinal. Métodos: se realizó un estudio descriptivo transversal, con el objetivo de demostrar la eficacia de la técnica de Halsted II en pacientes geriátricos con hernia inguinal en el Servicio de Cirugía General del Hospital Militar Clínico Quirúrgico Docente Octavio de la Concepción y de la Pedraja, Camagüey desde julio de 2014 a julio 2017. El universo estuvo constituido por 84 adultos mayores con hernia inguinal y la muestra fue de 72 pacientes. Resultados: en el estudio predominaron los hombres caucásicos entre 60 y 74 años de edad, con hernia indirecta con aumento del anillo interno, además del tabaquismo y las enfermedades pulmonares obstructivas crónicas. La infección de la herida quirúrgica fue la complicación temprana más frecuente, sin ser significativo el número de rechazo al material de sutura no absorbible y recurrencia de la hernia. Conclusiones: la hernia inguinal en el adulto mayor, es más frecuente en los hombres blancos en edades comprendidas entre los 60 y 74 años. El tabaquismo y las enfermedades pulmonares obstructivas crónicas son factores de riesgo para padecer de hernia inguinal y a su vez son agentes asociados a la menor eficacia de la técnica. La herniorrafía de Halsted II es una técnica segura y eficiente en el adulto mayor, con escasa recurrencia y complicaciones postoperatorias.
ABSTRACT Background: the ideal treatment of inguinal hernia in geriatric patients remains a challenge. Objective: to evaluate the effectiveness of the Halsted II technique in geriatric patients with inguinal hernia. Methods: a cross-sectional descriptive study was carried out, with the objective of demonstrating the effectiveness of the Halsted II technique in geriatric patients with inguinal hernia in the General Surgery Service of the Teaching Surgical Clinical Military Hospital Octavio de la Concepción y La Pedraja, Camagüey, in the period from July 2014 to July 2017. The universe consisted of 84 older adults with inguinal hernia and the sample was 72 patients. Results: the study was dominated by Caucasian men between 60 and 74 years of age, with indirect hernia with increased internal ring, in addition to smoking and chronic obstructive pulmonary diseases. Infection of the surgical wound was the most frequent early complication, without being significant the number of rejection to the non-absorbable suture material and recurrence of the hernia. Conclusions: inguinal hernia in the elderly is more common in white men between the ages of 60 and 74. Smoking and chronic obstructive pulmonary diseases are risk factors for suffering from inguinal hernia and in turn are agents associated with the lower efficacy of the technique. Halsted II herniorrhaphy is a safe and efficient technique in the elderly, with low recurrence and postoperative complications.
RESUMEN
Several European countries have established criteria for prioritising initiation of treatment in patients infected with the hepatitis C virus (HCV) by grouping patients according to clinical characteristics. Based on neural network techniques, our objective was to identify those factors for HIV/HCV co-infected patients (to which clinicians have given careful consideration before treatment uptake) that have not being included among the prioritisation criteria. This study was based on the Spanish HERACLES cohort (NCT02511496) (April-September 2015, 2940 patients) and involved application of different neural network models with different basis functions (product-unit, sigmoid unit and radial basis function neural networks) for automatic classification of patients for treatment. An evolutionary algorithm was used to determine the architecture and estimate the coefficients of the model. This machine learning methodology found that radial basis neural networks provided a very simple model in terms of the number of patient characteristics to be considered by the classifier (in this case, six), returning a good overall classification accuracy of 0.767 and a minimum sensitivity (for the classification of the minority class, untreated patients) of 0.550. Finally, the area under the ROC curve was 0.802, which proved to be exceptional. The parsimony of the model makes it especially attractive, using just eight connections. The independent variable "recent PWID" is compulsory due to its importance. The simplicity of the model means that it is possible to analyse the relationship between patient characteristics and the probability of belonging to the treated group.
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Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antivirales/uso terapéutico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Aprendizaje Automático , Adolescente , Adulto , Anciano , Coinfección , Técnicas de Apoyo para la Decisión , Femenino , Estudios de Seguimiento , VIH/genética , Hepacivirus/genética , Humanos , Masculino , Persona de Mediana Edad , Redes Neurales de la Computación , Estudios Prospectivos , España , Adulto JovenRESUMEN
Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis in both developed and developing countries. This infectious disease has a high prevalence and incidence in Europe. HEV infection has a greater clinical impact in vulnerable populations, such as immunosuppressed patients, pregnant women and patients with underlying liver disease. Therefore, the Study Group for Viral Hepatitis (Grupo de Estudio de Hepatitis Víricas, GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, SEIMC) believed it very important to prepare a consensus document to help in decision-making regarding diagnosis, clinical and therapeutic management, and prevention of HEV infection.