Impact of interferon-free therapies in HIV/HCV co-infected patients on real clinical practice: results from a multicenter region-wide cohort study (2014-2018).

BACKGROUND: Here, we assess the efficacy and safety of direct antiviral agents (DAAs) in a real-world cohort of co-infected individuals, and evaluate the consistency between clinical practice and guideline recommendations. METHODS: Multicenter, prospective cohort study of HIV/HCV co-infected patients followed-up in nine sites in Spain. All patients with detectable HCV-RNA naive to second-generation DAAs were enrolled. The primary endpoint was the assessment of sustained virological response at week 12 (SVR12). We performed intention-to-treat (ITT), per-protocol (PP), and multivariable analyses to identify factors associated with therapeutic failure. We compared the DAAs we administered to available guideline recommendations. Schemes not perfectly adjusted to the recommendations were defined as sub-optimal. RESULTS: Overall, 316 patients (82.1% male) received a total of 330 treatments. Of these, 43.9% were cirrhotic and 40.6% were treatment-experienced. In the ITT and PP analyses, SVR12 was achieved in 90.9% [95% confidence interval (CI) 87.3-93.6] and 93.7% (95% CI 90.5-95.6), respectively. Only alcohol abuse [odds ratio (OR): 0.33; 95% CI 0.138-0.789, P = 0.013] and a higher basal bilirubin level (OR: 0.595; 95% CI 0.416-0.851, P = 0.004) were independently associated to therapeutic failure. A progressive decrease in the proportion of sub-optimal treatments was observed over time, from 75% in 2014 to 0% in 2018. Being treated with a sub-optimal regimen was not associated with failure. CONCLUSION: Despite numerous difficulties in treatment access and in adaptation to the changing guidelines, we detected no differences among the DAAs used, nor did we detect a lower efficacy when the chosen treatment was not optimal.

Does fibrosis really regress in HIV/hepatitis C virus co-infected patients after treatment with direct antiviral agents?

OBJECTIVE: To evaluate the progression of liver stiffness after treatment with direct antiviral agents (DAAs), to identify predictive factors of fibrosis regression and to analyze the changes of scores AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) after treatment. DESIGN: Multicenter prospective cohort study of HIV/HCV co-infected patients conducted within the GECMEI cohort, Spain. METHODS: Individuals were eligible if they were willing to start DAAs and underwent two transient elastographies: at baseline and after the end of treatment (EOT). All patients with detectable HCV RNA naïve to DAAs were consecutively enrolled from nine medical hospitals. Liver stiffness results were categorized in four Metavir stages (F1: <7.1; F2 : 7.1--9.5; F3 : 9.5--2.4; F4: >12.4 kPa). The APRI and FIB-4 scores were calculated at baseline, EOT and 12 weeks after EOT. RESULTS: One hundred and seventy-eight patients were examined throughout a follow-up of 16.3 months (IQR: 12.5-25). The median of liver stiffness decrease was 2.6 kPa (IQR: 0-6.3). A greater improvement was observed in F3-F4 compared with F1-F2, (6.4 vs. 0.91 kPa, P < 0.001; P = 0.001, respectively). A decline between baseline and EOT measures was observed in APRI and FIB-4 (P < 0.001). Sustained virological response (SVR12) achievement was the only predictor of fibrosis regression [OR:17.4 (95% CI: 1.8-164.6; P = 0.013)]. CONCLUSION: Most patients experienced a significant reduction of liver stiffness and APRI and FIB-4 scores. This improvement was greater in those with advanced liver disease. SVR12 was the only predictor of fibrosis regression. The significance of this reduction is unclear and could reflect a decline in inflammation rather than true fibrosis regression.

Efectividad del tratamiento con agentes antivirales directos en pacientes con coinfección por VHC y VIH. Estudio de cohorte multicéntrico / Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study

Introducción: la eficacia de los agentes antivirales directos (AAD) ha quedado demostrada en ensayos clínicos tanto en mono como en coinfectados. Nuestro objetivo es analizar la efectividad y toxicidad de este tratamiento en vida real en pacientes con coinfección por VIH y VHC así como determinar variables asociadas a una evolución desfavorable. Métodos: estudio ambispectivo multicéntrico en una cohorte de pacientes coinfectados. Los datos fueron recogidos en ocho centros de Castilla-La Mancha entre 2014 y 2016. Se realizó un análisis por intención de tratamiento en el que cualquier pérdida de seguimiento, abandono de tratamiento o toxicidad terapéutica se consideró fracaso. Resultados: se estudiaron 229 pacientes con una mediana de edad de 49,6 años con predominio masculino (83%). Menos de un 10% presentaba carga viral (CV) detectable para el VIH. El genotipo de VHC más prevalente fue el 1 (65,1%). Un 50% tenía hepatopatía en grado de cirrosis. El 65% presentaba más de 800.000 copias/ml de CV de VHC. La respuesta viral sostenida (RVS) se alcanzó globalmente en el 91,7%. La estrategia de AAD más utilizada fue sofosbuvir/ ledipasvir. Un 52% de las pautas incluyeron ribavirina. El 65,9% completó pautas de 12 semanas y un 30%, de 24 semanas. Hubo 19 fracasos terapéuticos. No existen diferencias entre las distintas estrategias de AAD utilizadas. No se observó ningún factor predictor independiente de RVS. Conclusiones: el tratamiento del VHC en pacientes coinfectados presenta tasas de RVS muy elevadas también en vida real. La toxicidad es excepcional. No hemos identificado factores predictores específicos de evolución desfavorable (AU)

ntroduction: The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. Methods: This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. Results: A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. Conclusions: HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome (AU)

Effectiveness of direct-acting antiviral therapy in patients with a HCV/HIV coinfection. A multicenter cohort study.

INTRODUCTION: The effectiveness of direct-acting antiviral (DAA) agents has been demonstrated in clinical trials both in patients with mono and coinfections. The goal of the study was to analyze the effectiveness and toxicity of this therapy in real-life patients with a HIV/HCV coinfection and to identify variables that are associated with an unfavorable outcome. METHODS: This was a multicenter ambispective study in a cohort of coinfected patients. Data were collected from eight centers in Castilla-La Mancha from 2014 to 2016. An intent-to-treat analysis was performed and any loss to follow-up, treatment withdrawal or toxicity was considered as a failure. RESULTS: A total of 229 patients were included with a median age of 49.6 years and the majority were male (83%). Fewer than 10% had a detectable HIV-related viral load (VL). The most prevalent HCV genotype was 1 (65.1%). Fifty percent had cirrhotic liver disease and 65% had over 800,000 copies/ml of HCV VL. The global sustained viral response (SVR) was reached by 91.7% of cases. The most commonly used DAA regimen was sofosbuvir/ledipasvir. Ribavirin was included in 52% of regimens, 65.9% of cases completed 12-week regimens and 30% completed 24-week schemes. There were 19 therapy failures. No differences were observed between the various DAA strategies used. No independent predictor was found for SVR. CONCLUSIONS: HCV treatment in coinfected patients is highly successful in terms of SVR rate in the real-life setting and toxicity is exceptional. We identified no specific predictors of an unfavorable outcome.

HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study.

OBJECTIVE: HIV/HCV-coinfected patients and hepatitis C virus (HCV) monoinfected subjects are thought to respond equally to direct-acting antiviral (DAA)-based therapy despite the lack of data derived from clinical trials. This study is aimed to evaluate the impact of HIV coinfection on the response to DAA-based treatment against HCV infection in the clinical practice. PATIENTS AND METHODS: In a prospective multicohort study, patients who initiated DAA-based therapy at the Infectious Disease Units of 33 hospitals throughout Spain were included. The primary efficacy outcome variables were the achievement of sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12). RESULTS: A total of 908 individuals had reached the SVR12 evaluation time-point, 426 (46.9%) were HIV/HCV-coinfected, and 472 (52%) received interferon (IFN)-free therapy. In an intention-to-treat analysis, SVR12 rates in subjects with and without HIV-coinfection were 55.3% (94/170 patients) versus 67.3% (179/266 subjects; p = 0.012) for IFN-based treatment and 86.3% (221/256 subjects) versus 94.9% (205/216 patients, p = 0.002) for IFN-free regimens. Relapse after end-of-treatment response to IFN-free therapy was observed in 3/208 (1.4%) HCV-monoinfected subjects and 10/231 (4.4%) HIV/HCV-coinfected individuals (p = 0.075). In a multivariate analysis adjusted for age, sex, transmission route, body-mass index, HCV genotype, and cirrhosis, the absence of HIV-coinfection (adjusted odds ratio: 3.367; 95% confidence interval: 1.15-9.854; p = 0.027) was independently associated with SVR12 to IFN-free therapy. CONCLUSIONS: HIV-coinfection is associated with worse response to DAA-based therapy against HCV infection. In patients receiving IFN-free therapy, this fact seems to be mainly driven by a higher rate of relapses among HIV-coinfected subjects.

[Delayed diagnosis of HIV infection in the Spanish VACH cohort [1997-2002]]. / Diagnóstico tardío de la infección por el virus de la inmunodeficiencia humana en la Cohorte VACH (1997-2002).

OBJECTIVE: To study the prevalence of delayed diagnosis of HIV infection and associated factors. METHODS: A cross sectional study of patients included in the Spanish VACH cohort who had been diagnosed with HIV infection between 1997 and 2002 was performed. Delayed diagnosis was defined as patients diagnosed with HIV infection and AIDS simultaneously or within the first month after the first positive serologic test, or those with a first CD4+ cell count below 200/ml. The epidemiological characteristics of these patients were compared with those of the remaining patients RESULTS: Of 2,820 new cases of HIV infection, delayed diagnosis was found in 506 (18%). These patients differed from the remaining patients in their lower mean age and higher HIV viral load, as well as in their distribution by sex (higher proportion of males), occupational status, history of incarceration in prison, and HIV-risk transmission group. The median survival during follow-up was significantly lower among AIDS patients with a delayed diagnosis. CONCLUSIONS: Delayed diagnosis remains a cause for concern in our environment, due to its magnitude and its association with mortality. Some epidemiological characteristics provide clues to guide future programs directed at increasing information and improving prevention.

Diagnóstico tardío de la infección por el virus de la inmunodeficiencia humana en la Cohorte VACH (1997-2002) / Delayed diagnosis of HIV infection in the Spanish VACH cohort [1997-2002]

Objetivo: Estudiar la prevalencia del diagnóstico tardío (DT) de la infección por el virus de la inmunodeficiencia humana (VIH) y sus factores asociados. Métodos: Estudio transversal sobre los pacientes incluidos en la cohorte VACH cuya infección por el VIH hubiese sido diagnosticada entre 1997 y 2002. Consideramos DT los casos diagnosticados de sida concomitantemente o dentro del primer mes desde la primera serología positiva, o con recuento de CD4+ < 200/ml. Comparamos sus características epidemiológicas con las de los demás pacientes. Resultados: De 2.820 nuevos casos de infección por el VIH, 506 (18%) tuvieron DT. Éstos difirieron del resto en su menor edad media, mayor carga viral y en su distribución por sexos (mayor proporción de hombres), situación laboral, antecedentes penitenciarios y grupo de riesgo. La mediana de supervivencia durante el seguimiento fue menor en el grupo de DT. Conclusiones: El DT continúa siendo un problema preocupante por su magnitud y asociación con la mortalidad. Algunas características epidemiológicas proporcionan indicios para orientar futuros programas de información y prevención

Objective: To study the prevalence of delayed diagnosis of HIV infection and associated factors. Methods: A cross sectional study of patients included in the Spanish VACH cohort who had been diagnosed with HIV infection between 1997 and 2002 was performed. Delayed diagnosis was defined as patients diagnosed with HIV infection and AIDS simultaneously or within the first month after the first positive serologic test, or those with a first CD4+ cell count below 200/ml. The epidemiological characteristics of these patients were compared with those of the remaining patients Results: Of 2,820 new cases of HIV infection, delayed diagnosis was found in 506 (18%). These patients differed from the remaining patients in their lower mean age and higher HIV viral load, as well as in their distribution by sex (higher proportion of males), occupational status, history of incarceration in prison, and HIV-risk transmission group. The median survival during follow-up was significantly lower among AIDS patients with a delayed diagnosis. Conclusions: Delayed diagnosis remains a cause for concern in our environment, due to its magnitude and its association with mortality. Some epidemiological characteristics provide clues to guide future programs directed at increasing information and improving prevention