Liver-related mortality and hospitalizations attributable to chronic hepatitis C virus coinfection in persons living with HIV

[Abstract] Objectives. The aim of this study was to compare liver-related mortality and liver-related hospitalizations for persons living with HIV (PLWH) with and without hepatitis C virus (HCV) exposure, and to estimate the fraction of liver disease attributable to chronic HCV coinfection. Methods. An ambispective cohort study followed PLWH between 1993 and 2014. PLWH were classified into three groups: those who were HIV-monoinfected, those who cleared HCV spontaneously and those with chronic HCV coinfection. Liver-related mortality was estimated for the three groups and compared with the adjusted standardized mortality ratio. Results. Data for 2379 PLWH were included in the study (1390 monoinfected individuals, 146 spontaneous HCV resolvers and 843 with chronic HCV coinfection). Global mortality was 33.8%, 21.4% of which was liver-related. Patients who died from liver-related causes were mostly on antiretroviral therapy and had an undetectable HIV viral load when they died. The liver-related mortality rate in those with chronic HCV coinfection was 10.01 per 1000 patient-years vs. 3.84 per 1000 patient-years in the HIV-monoinfected group (P < 0.001). The adjusted standardized mortality ratio in the chronically HCV-coinfected group was 4.52 (95% confidence interval 2.98–5.86). The fractions of liver-related mortality and liver-related hospitalizations attributable to chronic HCV coinfection were 0.61 and 0.74, respectively. There were no differences in liver-related events between HIV-monoinfected individuals and those who spontaneously cleared HCV. Conclusions. Chronic HCV infection increases the risk of liver-related mortality and liver-related hospitalizations in PLWH, despite good control of HIV infection. Sixty per cent of liver-related mortality in chronically HCV-coinfected PLWH could be attributable to chronic HCV infection. The effect of mass HCV eradication with new therapies should be evaluated.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/0032

Cancer incidence in persons living with HIV

Correspondenc

Tendencia de las hospitalizaciones, reingresos y mortalidad intrahospitalaria en los pacientes infectados por VIH entre 1993-2013: impacto de la coinfección por el virus de la hepatitis C

[Abstract] Background. New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. Methods. A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993–2002 and 2003–2013) to be compared by conducting a comparative cross-sectional analysis. Results. A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36 ± 11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5–16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003–2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P < .001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). Conclusions. Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period.[Resumen] Introducción. Los cambios en las características epidemiológicas de los pacientes con infección por el VIH, y la introducción del tratamiento antirretroviral de alta eficacia, han modificado el perfil de las hospitalizaciones en esta población. El objetivo del estudio fue evaluar las tendencias en hospitalización, reingreso y mortalidad en pacientes VIH, y analizar el papel de la coinfección por el VHC. Métodos. Estudio de cohortes retrospectivo, que incluyó todas las hospitalizaciones de pacientes VIH entre 1993-2013. El estudio fue dividido en 2 periodos (1993-2002 y 2003-2013) para ser comparados mediante un análisis transversal. Resultados. Se analizaron 22.901 pacientes/años, que presentaron 6.917 hospitalizaciones que correspondieron a 1.937 pacientes (75% varones, edad media 36 ± 11 años, 37% coinfectados VIH/VHC). La mediana de estancia hospitalaria fue de 8 días (5-16), y la tasa de reingreso a los 30 días del 20,1%. Se observó un descenso significativo en el segundo periodo (2003-2013) de las hospitalizaciones motivadas por enfermedades infecciosas y trastornos psiquiátricos, y un incremento de aquellas relacionadas con neoplasias, enfermedad cardiovascular, gastrointestinal y enfermedades respiratorias crónicas. La mortalidad intrahospitalaria permanece elevada (6,8% en el primer periodo vs. 6,3% en el segundo), con un aumento progresivo de las muertes por enfermedades no definitorias de sida (37,9 vs. 68,3%; p < 0,001). La tasa de hospitalización disminuyó de manera significativa después de 1996 (4,9% anual), pero este descenso fue menos acusado en los pacientes coinfectados VIH/VHC (1,7% anual). Conclusiones. Las hospitalizaciones motivadas por enfermedades infecciosas y trastornos psiquiátricos han descendido; por el contrario, se observó un aumento significativo de aquellas relacionadas con neoplasias no definitorias de sida, enfermedad cardiovascular y enfermedades respiratorias crónicas. La mortalidad intrahospitalaria permanece a día de hoy elevada, pero a expensas fundamentalmente de enfermedades no definitorias de sida. La coinfección VIH/VHC incrementó los días de hospitalización y los reingresos durante el periodo de estudio.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/0032

Teleconsultation for the pharmaceutical care of HIV outpatients in receipt of home antiretrovirals delivery: clinical, economic, and patient-perceived quality analysis

Observational study[Abstract] Background/Introduction: Pharmacist teleconsultations, combined with home drug delivery or mail-order pharmacy (MOP), can help hospital outpatients with difficulties accessing treatment. The objectives of this study are to describe a teleconsultation protocol and to evaluate clinical, economic, and patient-perceived quality results. Materials and Methods: A cohort observational study was carried out for 3 years on HIV outpatients. Clinical variables were adherence, plasma HIV-RNA, and CD4+ levels. A pharmacoeconomic analysis was carried out through a cost-minimization study. Patient-perceived quality was assessed through a satisfaction survey. Simple random sampling was performed for 95% safety, accuracy ±1%, and losses ±20%. Results: The 38 participants (sample size) consisted of 82% male patients, aged 44.7 ± 8.4 years. There were 854 teleconsultations and 100% treatment adherence. All HIV outpatients kept virally suppressed (p = 1.00) and maintained a controlled immunological level (p = 0.87). The economic evaluation revealed 137 ± 23 € patient/year costs-saved and 18.5 ± 7.2 h/patient/year working time gained. Patient-perceived quality average score was >9.4 out of 10 in all items; the most valued factors were the saving of direct costs and reconciliation with work commitments (45%) and the least valued attributes were making the payment for the shipment and having to adjust to a telephone appointment (41%). Discussion/Conclusions: A teleconsultation protocol associated with home antiretrovirals delivery or MOP obtains a high degree of satisfaction from the HIV hospital outpatients receiving treatment, without repercussions on the therapeutic objectives and with the saving of important direct costs for the patient and indirect costs in relation to labor productivity

Caracterización epidemiológica, clínica y virológica de los nuevos diagnósticos de infección por VHC en Galicia (2014-2015)

Abstrac

Liver-related events and mortality among elderly patients with advanced chronic hepatitis C treated with direct-acting antivirals

Research article[Abstract] BACKGROUND: Direct-acting antivirals (DAAs) are effective in patients aged ≥65 years. However, little is known about the effects of DAAs on survival, liver decompensation and development of hepatocellular carcinoma (HCC). OBJECTIVE: To compare the incidence of liver-related events and mortality between patients aged ≥65 and <65 years. METHODS: Prospective study comparing patients aged ≥65 and <65 years treated with DAAs. The incidence of liver-related events and mortality, and HCC was compared between age groups. RESULTS: Five hundred patients (120 aged ≥65 and 380 aged <65 years) were included. The incidence of liver-related events was 2.62 per 100 patient-years (py) in older and 1.41/100 py in younger patients. All-cause mortality was 3.89 and 1.27/100 py in older and younger patients, respectively. The respective liver-related mortality rates were 1.12 and 0.31/100 py. In patients with cirrhosis (stage F4), all-cause mortality (P = 0.283) and liver-related mortality (P = 0.254) did not differ between groups. All five liver-related deaths were related to multifocal HCC. The incidence of HCC was 1.91 and 1.43 per 100 py in the older and younger groups, respectively (P = 0.747). The diagnosis of HCC was 8 months after the end of treatment. CONCLUSIONS: The incidence of liver-related events and liver-related mortality was low in older people treated with DAAs and was similar to that in younger patients. The extra mortality in people aged ≥65 years treated with DAAs seems to be secondary to non-liver-related causes. These results support the utilization of DAAs in patients aged ≥65 years.Instituto de Salud Carlos III; JR17/0002

Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?

[Abstract] Objectives. The objective of this study was to evaluate the prevalence of blips and risk of virological failure (VF) among HIV-infected patients with sustained virological suppression (HIV-RNA <50 copies/mL) on ART. Methods. Newly diagnosed (2004–13) HIV-infected patients with sustained virological suppression on ART (minimum follow-up of 3 months) were identified. Risk of VF was evaluated according to different plasma HIV-RNA quantification values based on the limits of quantification/detection of current commercial assays (20 copies/mL). Kaplan–Meier and Cox proportional hazards models were used to compare the cumulative incidence of VF. Results. A total of 565 newly diagnosed HIV-infected patients were identified: 453 started ART and 354 achieved virological suppression. Prevalence of blips (isolated HIV-RNA ranging from 50 to 200 copies/mL) and VF (HIV-RNA ≥50 copies/mL) was 22.7% and 8.8%, respectively (mean follow-up of 42 months). Multivariate analysis identified differences between HIV-RNA values as an independent predictor of VF (P = 0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524–11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA 200 copies/mL [33.7% at 24 and 60 months versus <5% for other HIV-RNA values; HR 6.943 (0.728–66.261), P = 0.092]. Conclusions. Blips are frequent (22.7%) among HIV-infected patients with sustained virological suppression on ART. HIV patients with blips and at least three consecutive detected, but not quantified, HIV-RNA determinations (<20 copies/mL) had a higher risk of VF. These findings highlight the relevance of maintaining HIV-RNA levels below the limits of quantification of current assays (<20 copies/mL).Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/0226

Efectividad y seguridad de daclatasvir/ sofosbuvir con o sin ribavirina en pacientes infectados por el genotipo 3 del virus de la hepatitis C: resultados en práctica clínica real

[Abstract] OBJECTIVE: Direct-acting antivirals have shown high efficacy in all hepatitis C virus (HCV) genotypes, but genotype 3 (G3) treatments continue to be a challenge, mainly in cirrhotic patients. The aim of this study is to analyse effectiveness and safety of daclatasvir associated with sofosbuvir with or without ribavirin in G3-HCV infected patients in real clinical practice. METHODS: An observational, prospective, cohort study over 2.5 years, in G3-HCV infected adult patients, in all fibrosis stages including patients with decompensated cirrhosis. Treatment was a combination of sofosbuvir 400 mg/day + daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events. RESULTS: A total of 111 patients were enrolled, 32.4% cirrhotics and 29.9% treatment-experienced. The global SVR12 rate was 94.6%, while the SVR12 rate in F3-4 fibrosis stage patients was 90.8% versus 100% in patients with F0-2 fibrosis (p=0.03). In cirrhotic patients, SVR12 was 100% versus 40% depending on whether ribavirin was added or not to daclatasvir/sofosbuvir (p=0.001). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed. CONCLUSIONS: Daclatasvir/sofosbuvir ± ribavirin is highly effective in G3-HCV infected patients. Advanced degrees of fibrosis significantly decrease the effectiveness of this treatment, which motivates the need for the addition of ribavirin in cirrhotic patients. The regimen was safe and well tolerated.[Resumen] OBJETIVOS: Los antivirales de acción directa han demostrado una alta eficacia en todos los genotipos del virus de la hepatitis C (VHC), pero los tratamientos para el genotipo 3 (G3) siguen siendo un desafío, principalmente en pacientes cirróticos. El objetivo de este estudio es analizar la efectividad y la seguridad del daclatasvir asociado con sofosbuvir con o sin ribavirina en pacientes infectados por G3-VHC en la práctica clínica real. PACIENTES Y MÉTODOS: Estudio observacional, prospectivo, de cohorte de más de 2,5 años, en pacientes adultos infectados con G3-VHC, en todos los estadios de fibrosis, incluidos los pacientes con cirrosis descompensada. El tratamiento fue una combinación de sofosbuvir 400 mg / día + daclatasvir 60 mg / día, con o sin una dosis de ribavirina ajustada por peso durante 12 o 24 semanas. El criterio de valoración principal de eficacia fue la tasa de respuesta virológica sostenida 12 semanas después del tratamiento (RVS12). La variable principal de seguridad fue la tasa de suspensiones de tratamiento secundaria a eventos adversos graves. RESULTADOS: Se incluyeron 111 pacientes, 32.4% cirróticos y 29.9% con experiencia previa de tratamiento antiviral. La tasa global de RVS12 fue del 94,6%, mientras que la tasa de RVS12 en pacientes con estadio de fibrosis F3-4 fue del 90,8% frente al 100% en pacientes con fibrosis F0-2 (p = 0,03). En pacientes cirróticos, la RVS12 fue del 100% en comparación con el 40%, dependiendo de si se agregó o no ribavirina a daclatasvir / sofosbuvir (p = 0,001). Ninguna otra variable basal del paciente o del tratamiento influyó en la efectividad del tratamiento. No se observó ninguna suspensión del tratamiento secundario a eventos adversos graves. CONCLUSIONES: Daclatasvir / sofosbuvir ± ribavirina es altamente efectivo en pacientes infectados por G3-VHC. Los grados avanzados de fibrosis disminuyen significativamente la efectividad de este tratamiento, lo que motiva la necesidad de la adición de ribavirina en pacientes cirróticos. El régimen fue seguro y bien tolerado

Darunavir/cobicistat maintains the effectiveness of darunavir/ritonavir in HIV-infected patients under mono or dual therapy

[Abstract] OBJECTIVES: Darunavir/ritonavir (DRV/r) in mono or dual therapy has proven efficacy in selected patients. The aim of this study was to evaluate the efficacy of switching from DRV/r to DRV/cobicistat (DRV/c) in patients under mono or dual therapy. METHODS: This was a prospective multicenter cohort study of patients using DRV/r under mono or dual therapy plus lamivudine who changed to DRV/c maintaining the previous regimen. All patients had a controlled HIV viral load (<50 copies/ml) when switched and were examined every 12 weeks. The primary end-point was the percentage of participants without virological failure (VF) at week 48 in the intent-to-treat analysis. The CD4 cell count and concentrations of cholesterol, triglyceride, and creatinine were measured from baseline to week 48. RESULTS: A total of 162 patients were included: 68.5% were men, and their mean age was 46 ± 12 years. Seventy (43.2%) patients were treated with DRV/r monotherapy, and 92 (56.8%) were treated with DRV/r plus lamivudine. The efficacy at week 48 was 95.1% (95% CI: 90.6%-97.5%) in the intent-to-treat analysis and 98.7% (95.5-99.6%) in the on-treatment analysis. Two VFs were documented but without development of resistance mutations. No significant changes were found in the lipid profile. Creatinine concentration increased significantly by 0.07 mg/dl (0.04-0.10, P < 0.001). CONCLUSIONS: Switching from DRV/r to DRV/c in patients under mono or dual therapy is safe and effective.Instituto de Salud Carlos III; JR17/0002

Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients

Short communication[Abstract] Background. New direct-acting antivirals agents (DAAs) are very safe and well tolerated. Objectives. The purpose of this study is to analyse the efficacy and safety of DAAs in elderly patients, who have co-morbidities and are on chronic medications. Study design. All HCV-infected patients over 65 years old in clinical follow-up at two Hospitals in Spain who initiated anti-HCV therapy were included (August 2012–October 2015). Results. A total of 120 HCV mono-infected patients were recorded. Mean age of patients was 72.6 ± 7.4 years. There were 53.3% women and GT1b was the most frequent (83.3%); 64.2% had cirrhosis and 42.5% were treatment experienced. Ombitasvir + Paritaprevir/r ± Dasabuvir ± Ribavirin (RBV) and sofosbuvir/ledipasvir ± RBV were the most frequently used regimens. Weight-adjusted dosing of RBV was included in 61.7% and 43.6% of them required a dose reduction. Most of the patients (86.7%) had concomitant chronic medication and in 35.8% adjustment was necessary. Adverse events (AE) were seen in 65% of the patients; more frequent when a protease inhibitor (PI) was being used. The sustained virological response (SVR12) per ITT was 88.3%. Only 3 patients discontinued treatment and 2 patients died. Conclusions. High rates of SVR12 (88.3%) were observed among elderly patients with DAAs-based regimens. The presence of AE was frequent (65%). The majority of these patients (86.7%) had concomitant medication that required adjustment in 1/3 of them. These findings highlight the high rates of response to DAAs in the elderly HCV-population. However, special caution must be taken when using RBV and a PI.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM15/0023