Prevalence of Risk of Malnutrition and Risk of Sarcopenia in a Reference Hospital for COVID-19: Relationship with Mortality.

INTRODUCTION: Many elderly patients with COVID-19 are at risk of malnutrition. The aim of our study was to evaluate the risk of malnutrition and sarcopenia in elderly COVID-19 patients with the R-MAPP (Remote-Malnutrition APP). MATERIALS AND METHODS: A cross-sectional study of 337 consecutive outpatients ≥65 years who attended the Central Emergency COVID-19 Hospital of Castilla y Leon was conducted. In all patients, the protocol of R-MAPP (Malnutrition Universal Screening Tool [MUST] and Simple Questionnaire to Rapidly Diagnose Sarcopenia [SARC-F]) was realized. RESULTS: The mean age was 86.1 ± 8.7 years, with a sex distribution of 167 males (49.5%) and 170 females (51.5%). According to the MUST test, patients with 0 points have a low nutritional risk (n = 50, 14.8%), 1 point a medium nutritional risk (n = 19, 5.6%), and 2 or more points a high nutritional risk (n = 268, 79.6%). The SARC-F questionnaire generates patients with 4 or more points as predictive of sarcopenia (n = 304, 80.2%) and <4 points without prediction of sarcopenia (n = 33, 9.8%). Global mortality was 24.03% (n = 81). The mortality rate was related to the pathological SARC-F score ≥4 (27.1% vs. 3.1%; p = 0.01) and MUST score ≥2 (26.7% vs. 16.4%; p = 0.04). In the logistic regression analysis, only the SARC-F score ≥4 remained as an independent variable related to mortality; odds ratio was 8.34 (95% CI: 1.1-63.8; p = 0.04), adjusted for age, sex, albumin levels, and MUST test. CONCLUSIONS: During COVID-19 infection, hospitalized patients at risk of sarcopenia have a high risk of mortality and have a poor nutritional status.

DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.

BACKGROUND: Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naïve-HIV-infected patients. METHODS: We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience's MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value). RESULTS: All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028). CONCLUSIONS: DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naïve HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection.

Altered Underlying Renal Tubular Function in Patients With Chronic Hepatitis B Receiving Nucleos(t)ide Analogs in a Real-World Setting: The MENTE Study.

BACKGROUND: Cases of renal tubular dysfunction have been reported in patients with hepatitis B and in patients with human immunodeficiency virus who are undergoing tenofovir treatment. However, little is known about the impact on tubular function in patients with chronic hepatitis B (CHB) under long-term use of entecavir (ETV) and tenofovir disoproxil fumarate (TDF). We evaluated markers of renal tubular function and bone turnover in patients with CHB treated with ETV or TDF. PATIENTS AND METHODS: A multicenter, cross-sectional study was performed on markers of renal tubular function and bone turnover in hepatitis B virus-monoinfected patients on long-term treatment with Entecavir or Tenofovir (the MENTE study). The analyzed parameters were: retinol-binding protein/creatinine, neutrophil gelatinase-associated lipocalin/creatinine, excretion of phosphates, uric acid excretion, glomerular filtrate, protein/creatinine, albumin/creatinine, serum creatinine, phosphate, CTX, P1NP, vitamin D, and parathormone. RESULTS: A total of 280 patients (ETV: 89, TDF: 69, control: 122) were included in this study. The TDF group was associated with altered levels of retinol-binding protein (RBP)/creatinine (TDF 25% vs. 7% ETV and control; P<0.001). Protein/creatinine, uric acid excretion, P1NP1, and parathormone were higher in the TDF group. The proportion of patients with serum phosphate <2.5 mg/dL was higher in both the ETV and the TDF groups compared with the control. The multivariate analysis showed that the use of TDF was independently associated with a higher risk of altered excretion of RBP/creatinine (4.4; interquartile range: 1.4 to 14; P=0.013). CONCLUSIONS: We found an independent association between TDF use and altered RBP excretion. This finding indicates subclinical tubular damage. Because tubular dysfunction can precede the decline of renal function, close monitoring of RBP levels in patients with CHB on nucleos(t)ide analog treatment must be performed for early detection of TDF-related renal toxicity. In this study, these differences in tubular function were not associated with concomitant changes in markers of bone turnover.

Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers.

BACKGROUND AND AIM: There are few data of fibrosis development in chronic hepatitis B (CHB) patients classified as inactive carriers. The aim of this study is to determinate the prevalence of significant fibrosis and probable cirrhosis measured by FibroScan in real inactive CHB carriers and investigate the relationship with virological, epidemiological, and metabolic factors. METHODS: Cross-sectional cohort study including CHB inactive carriers. Liver stiffness measurement was performed with transient elastography (FibroScan). Significant fibrosis (≥ F2) was defined as stiffness > 7.5 kPa, and probable cirrhosis as > 11.8 kPa. Factors associated with significant fibrosis were explored with univariate and multivariate adjusted logistic regression analyses. RESULTS: Ninety-six CHB inactive carriers were analyzed. Of them, 24 (25%) had significant fibrosis and 7 (7%) probable cirrhosis; mean stiffness was 6.2 ± 2.3 kPa. Of them, 24% had metabolic syndrome, with higher FibroScan value than those without (8.4 kPa vs 5.5 kPa, P < 0.001). Factors associated with significant fibrosis were (odds ratio, 95% confidence interval, P value): central obesity (7.1, 1.8-27.9, 0.005), elevated fasting glucose (4.3, 1.3-27.9, 0.036), reduced high-density lipoprotein cholesterol (5.2, 1.2-23.6, 0.032) and elevated triglycerides (6.2, 1.4-28.3, 0.019). Factors as age, sex, transaminases, hepatitis B virus DNA or genotype were not related with liver fibrosis. The presence of metabolic syndrome has a 69% of positive predictive value and 89% of negative predictive value for significant fibrosis. CONCLUSION: Different components of metabolic syndrome are associated with fibrosis development in CHB inactive carriers. In the absence of metabolic syndrome, significant fibrosis is uncommon in this population.

Comparison of high ribavirin induction versus standard ribavirin dosing, plus peginterferon-α for the treatment of chronic hepatitis C in HIV-infected patients: the PERICO trial.

BACKGROUND: Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 µg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin ß (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. RESULTS: A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 µg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. CONCLUSIONS: A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.

[Malignancies in HIV-infected patients: descriptive study of 129 cases between 1993 and 2010]. / Neoplasias en pacientes con infección por VIH: Estudio descriptivo de 129 casos en el período 1993-2010.

INTRODUCTION: The development of malignancies is a problem associated with HIV infection. The incidence and spectrum of malignancies has been modified with the addition of highly active antiretroviral therapy (HAART). AIM: To describe the clinical and epidemiological characteristics and prognosis of HIV patients who have developed a malignancy. METHODS: Retrospective observational study was conducted in HIV + patients who developed a malignancy between 1993-2010 in a referral hospital. AIDS-defining malignancies (ADN) and non-AIDS-defining malignancies (NADN) were compared. RESULTS: 125 patients were identified with at least one malignancy. The most frequent malignancies were: non-Hodgkin lymphoma (n; 39; 30.2%), Kaposi's sarcoma (n: 20; 15.5%), Hodgkin's disease (n: 11; 8.8%), lung cancer (n: 20; 15.5%) and hepatocellular carcinoma (n: 9; 6.9 %). The mean age was 42 ± 11 years, 84% male, 55.8% were coinfected with HBV and or HCV. The risk behaviors were: 45.6% intravenous drug users, 16.8% men who have sex with men and 20% heterosexuals). There were 67 (52%) NADN and 62 (48%) ADN; NADN patients had a longer story of HIV infection and longer exposure to HAART, better level of immunodeficiency and better virological control than ADN patients. Four patients developed a second malignancy. Overall survival was 34.7%. CONCLUSIONS: We found an increased incidence of NADN, appearing in patients with better virological and immunological control than ADN group. Mortality of patients with HIV infection and malignancy is still very high.

Safety and Immunogenicity of SARS-CoV-2 vaccines in people with HIV.

OBJECTIVE: To evaluate the safety and the serological response after two doses of mRNA-based SARS-CoV-2 vaccination in people with HIV (PWH). METHODS: Participants were evaluated 4 weeks after the second dose of mRNA-1273 or BNT162b2 vaccine. Tolerability was evaluated with a specific adverse event questionnaire. Patient's sera were analysed using LIAISON SARS-CoV-2 TrimericS IgG (DiaSorin). RESULTS: One-hundred PWH were included, 75% of them men, with a mean age of 44 ±â€Š11 years old, all receiving antiretroviral treatment and mostly with controlled viral loads (98% with HIV RNA <50 copies/ml) and 96% had >200 CD4+/µl. All patients seroconverted after vaccination (antibody concentration ≥33.8 binding antibody units [BAU]/ml). Only 3% of the patients had a low antibody concentration (<520 BAU/ml), whereas 67% of them had concentrations above the assay's detection range (>2080 BAU/ml). Fifty-six patients had local or systemic symptoms, with mild arthromyalgia being the most common systemic symptom. No severe adverse events were reported. CONCLUSIONS: Vaccination with two doses of mRNA-1273 or BNT162b2 is well tolerated in PWH under effective antiretroviral treatment and it leads to a successful antibody response.

Analysis of the costs associated with the follow-up of HIV patients discontinuing antiretroviral treatment due to lack of effectiveness or unacceptable toxicity in Spain.

OBJECTIVE: To assess the use of resources and the costs associated with  following up patients infected with the human immunodeficiency virus after  discontinuation of an antiretroviral treatment and initiation of a new one due to  a lack of effectiveness or unacceptable toxicity, as compared to the costs  involved in the routine follow-up of patients on antiretroviral treatment, from  the Spanish National Health System perspective. Method: The use of resources (clinical tests, medical visits, and hospital pharmacy visits) associated with following three profiles of patients  infected with the human immunodeficiency virus (stable ones, those  discontinuing an existing antiretroviral treatment and being switched to a new  one due to a lack of effectiveness, and those discontinuing an existing antiretroviral treatment and being switched to a new one due to  unacceptable toxicity) was identified, based on clinical practice guidelines and  the findings of a multidisciplinary expert panel (n = 5). The experts agreed on  the main adverse events leading to discontinuation, classifying them into  gastrointestinal, renal, osseous, musculoskeletal, dermatological, hepatic, lipid  profile-related, neuropsychiatric and sexual alterations. Unit costs were  identified from official healthcare costs databases. The cost  (€, 2020) of  following up each patient profile was estimated, excluding the cost of the  antiretroviral treatment itself, with a time horizon of two years. RESULTS: The per-patient cost of following up stable patients over two years  was estimated at €4,148 (tests: €2,293; visits: €1,855). Patient follow-up after  discontinuation of an existing antiretroviral treatment and initiation of a  different one due to a lack of effectiveness was estimated at €5,434 (tests:  €2,777; visits: €2,657). The cost of follow-up after discontinuation of an  existing regimen and initiation of a new one due to unacceptable toxicity varied  according to the adverse event prompting the switch, ranging from  €4,690 for lipid profile dysregulation, to €5,304, for musculoskeletal  alterations. In this patient profile, the cost of tests ranged from €2,403 to  €3,017, and that of visits from €2,287 to €2,842. CONCLUSIONS: The cost associated with following up of patients infected with  the human immunodeficiency virus after discontinuation of an existing  antiretroviral regimen and initiation of a new one is higher than that of routine  follow-up, without taking the cost of drugs into account. The treatment  discontinuation rate is a relevant factor when selecting the most appropriate  therapy for each patient.

OBJETIVO: Estimar el uso de recursos y costes asociados al seguimiento de  pacientes con infección por el virus de la inmunodeficiencia humana tras  discontinuación del tratamiento antirretroviral actual debido a falta de  efectividad o toxicidad inaceptable y cambio a un nuevo tratamiento antirretroviral, comparado con el seguimiento habitual de los  pacientes con tratamiento antirretroviral, desde la perspectiva del Sistema  Nacional de Salud español.Método: Se identificó el uso de recursos (pruebas clínicas, visitas médicas,  visitas a la farmacia hospitalaria) asociado al seguimiento de pacientes con  infección por el virus de la inmunodeficiencia humana en tres perfiles de  pacientes (estable, discontinuación y cambio por falta de efectividad,  discontinuación y cambio por toxicidad inaceptable), a partir de las guías de  práctica clínica y un panel de expertos multidisciplinar (n = 5). Los expertos  consensuaron los principales eventos adversos que conducían a la  discontinuación, agrupándolos en: alteraciones gastrointestinales, renales,  óseas, musculoesqueléticas, dermatológicas, hepáticas y del perfil lipídico,  trastornos neuropsiquiátricos y sexuales. Los costes unitarios se identificaron a  partir de bases de datos oficiales  assode costes sanitarios y de la literatura.  Se estimó el coste (€, 2020) del seguimiento en cada perfil de paciente, sin  incluir el coste derivado del tratamiento antirretroviral, en un horizonte  temporal de dos años. RESULTADOS: El coste por paciente a dos años se estimó en 4.148 € (pruebas:  2.293 €; visitas: 1.855 €) para el seguimiento del paciente estable. El  seguimiento del paciente tras discontinuación por falta de efectividad y cambio  de tratamiento antirretroviral se estimó en 5.434 € (pruebas: 2.777 €; visitas:  2.657 €). El coste del seguimiento tras la discontinuación por toxicidad  inaceptable y cambio de tratamiento antirretroviral varió en función del evento  adverso que motivó el cambio, oscilando entre 4.690 € para las alteraciones  del perfil lipídico, y 5.304 € para las alteraciones musculoesqueléticas. En este  perfil de pacientes, las pruebas variaron entre 2.403 € y 3.017 € y las visitas  entre 2.287 € y 2.842 €. CONCLUSIONES: El coste asociado al seguimiento del paciente con infección por  el virus de la inmunodeficiencia humana tras discontinuación y cambio a un  nuevo tratamiento antirretroviral es mayor comparado con el seguimiento  habitual, sin tener en cuenta el coste farmacológico. La tasa de discontinuación  del tratamiento antirretroviral es un factor relevante a la hora  de seleccionar la terapia más adecuada para cada paciente.

Similar plasma lipidomic profile in people living with HIV treated with a darunavir-based or an integrase inhibitor-based antiretroviral therapy.

Cardiovascular disease is an important cause of morbidity and mortality in people living with HIV (PLWH), who commonly experience lipid disturbances. The aim of this study was to determine whether the plasma lipidomic profile differs between PLWH receiving a darunavir-based ART and those receiving integrase inhibitor-based ART. This was a cross-sectional study of unselected patients for whom metabolomic analysis was performed using ultra-high-performance liquid chromatography coupled to mass spectrometry. Data for the two subgroups were compared by calculating the log2 of the fold change for each metabolite and then grouping these into the main lipid families. Sixty-two PLWH aged 49.3 ± 8.6 years (82% men) were included: 12 patients (19.4%) had hypertension, 8 (12.9%) had type 2 diabetes, 25 (41.0%) had dyslipidaemia and 9 (14.5%) were taking statins, without significant differences in all these variables between the two groups. Twenty-five (40.3%) received darunavir-based ART and 37 (59.7%) integrase inhibitor-based ART. Although the differences were not statistically significant, patients treated with darunavir-based ART had higher concentrations of total cholesterol (211 mg/dL vs 194 mg/dL), LDL-cholesterol (132 mg/dL vs 117 mg/dL) and triglycerides (155 mg/dL vs 122 mg/dL), and lower HDL-cholesterol concentration (50 mg/dL vs 52 mg/dL). The main lipid families and metabolites differed slightly between groups (log2-fold change; P-value): ceramides (-0.07; 0.49), phosphatidylinositols (-0.05; 0.63), diacylglycerols (0.10; 0.64), phosphatidylethanolamines (0.03; 0.78), triacylglycerols (0.27; 0.18) and lysophosphatidylethanolamines (0.03; 0.83). In the integrase inhibitor-based group, the use of tenofovir alafenamide fumarate significantly increases the majority of lipid fractions, when compared with tenofovir disoproxil fumarate. The lipidomic profile did not differ between PLWH treated with darunavir-based or integrase inhibitor-based ART. This was especially true for ceramides, which are involved in cardiovascular disease. Further studies are needed to study the impact of ART in lipidomic profile.

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

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.

Predictors of Hepatitis C Treatment Failure After Using Direct-Acting Antivirals in People Living With Human Immunodeficiency Virus.

BACKGROUND: Little is known about the influence of ongoing barriers to care in the persistence of hepatitis C virus (HCV) viremia after treatment with direct-acting antivirals (DAAs) among people living with human immunodeficiency virus (PLWH). METHODS: We conducted a retrospective cohort analysis of PLWH treated through the standard of care in 3 Western countries, to investigate the predictors of HCV treatment failure (clinical or virologic), defined as having a detectable serum HCV ribonucleic acid within 12 weeks after DAA discontinuation. In addition to HCV and liver-related predictors, we collected data on ongoing illicit drug use, alcohol abuse, mental illness, and unstable housing. Logistic regression analyses were used to identify predictors of HCV treatment failure. RESULTS: Between January 2014 and December 2017, 784 PLWH were treated with DAA, 7% (n = 55) of whom failed HCV therapy: 50.9% (n = 28) had a clinical failure (discontinued DAA therapy prematurely, died, or were lost to follow-up), 47.3% (n = 26) had an HCV virologic failure, and 1 (1.8%) was reinfected with HCV. Ongoing drug use (odds ratio [OR] = 2.60) and mental illness (OR = 2.85) were independent predictors of any HCV treatment failure. Having both present explained 20% of the risk of any HCV treatment failure due to their interaction (OR = 7.47; P < .0001). Predictors of HCV virologic failure were ongoing illicit drug use (OR = 2.75) and advanced liver fibrosis (OR = 2.29). CONCLUSIONS: People living with human immunodeficiency virus with ongoing illicit drug use, mental illness, and advanced liver fibrosis might benefit from enhanced DAA treatment strategies to reduce the risk of HCV treatment failure.

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study.

BACKGROUND AND AIMS: Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. MATERIAL AND METHODS: Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. RESULTS: Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision. CONCLUSIONS: These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials.

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

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.

The 10-item eating assessment tool is associated with nutritional status, mortality and hospital stay in elderly individuals requiring hospitalization with acute diseases.

OBJECTIVE: the purpose of this investigation was to investigate the associations between nutritional status by Mini Nutritional Assessment (MNA) test and dysphagia by EAT-10 in elderly individuals requiring nutritional oral care in an acute hospital. PATIENTS: this was a cross-sectional survey covering a sample of 560 elderly individuals. As anthropometric parameters, weight and body mass index (BMI) have been included. Glucose, creatinine, sodium, potassium, albumin, prealbumin and transferrin serum levels were measured. The EAT-10 and MNA tests were carried out. The days of hospital stay and mortality were recorded. RESULTS: the mean EAT-10 was 11.2 ± 0.89, the median was 10 and the interquartile range, 6-15. A total of 465 (83.1%) elderly patients had EAT-10 scores between 3 and 40, indicating the presence of dysphagia. The mean MNA test was 15.2 ± 1.1, median was 15 and interquartile rage, 11-18.5. According to their MNA score, a total of 340 (60.7%) elderly patients had MNA scores under 17 (malnutrition) and 177 subjects (31.6%) had a MNA score of 17-23.5 (risk of malnutrition). The MNA score and EAT-10 score were independently associated with hospital stance Beta -0.111 (CI 95%: -0.031- -0.78) and Beta 0.122 (CI 95%: 0.038-0.43), respectively. MNA score was associated with EAT-10 score Beta -0.236 (CI 95%: -0.213-0.09). The MNA score and EAT-10 score were independently associated with mortality odds ratio 0.91 (CI 95%: 0.84-0.96) and 1.040 (CI 95%: 1.008-1.074), respectively. CONCLUSION: dysphagia assessed by the EAT-10 is associated with nutritional status in elderly subjects requiring acute hospitalization. Subsequently, malnutrition and dysphagia were associated with poor outcome such as hospital stay and mortality.

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

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±7.4years. 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.

Análisis de los costes asociados al seguimiento de pacientes con VIH que discontinúan el tratamiento antirretroviral por falta de eficacia o toxicidad inaceptable en España / Analysis of the costs associated with the follow-up of HIV patients discontinuing antiretroviral treatment due to lack of effectiveness or unacceptable toxicity in Spain

Objetivo: Estimar el uso de recursos y costes asociados al seguimientode pacientes con infección por el virus de la inmunodeficiencia humanatras discontinuación del tratamiento antirretroviral actual debido a faltade efectividad o toxicidad inaceptable y cambio a un nuevo tratamientoantirretroviral, comparado con el seguimiento habitual de los pacientescon tratamiento antirretroviral, desde la perspectiva del Sistema Nacionalde Salud español.Método: Se identificó el uso de recursos (pruebas clínicas, visitasmédicas, visitas a la farmacia hospitalaria) asociado al seguimiento depacientes con infección por el virus de la inmunodeficiencia humana entres perfiles de pacientes (estable, discontinuación y cambio por faltade efectividad, discontinuación y cambio por toxicidad inaceptable), apartir de las guías de práctica clínica y un panel de expertos multidisciplinar (n = 5). Los expertos consensuaron los principales eventos adversos que conducían a la discontinuación, agrupándolos en: alteracionesgastrointestinales, renales, óseas, musculoesqueléticas, dermatológicas,hepáticas y del perfil lipídico, trastornos neuropsiquiátricos y sexuales.Los costes unitarios se identificaron a partir de bases de datos oficiales de costes sanitarios y de la literatura. Se estimó el coste (€, 2020) delseguimiento en cada perfil de paciente, sin incluir el coste derivado deltratamiento antirretroviral, en un horizonte temporal de dos años.Resultados: El coste por paciente a dos años se estimó en 4.148 €(pruebas: 2.293 €; visitas: 1.855 €) para el seguimiento del pacienteestable. (AU)

Objective: To assess the use of resources and the costs associatedwith following up patients infected with the human immunodeficiency virusafter discontinuation of an antiretroviral treatment and initiation of a newone due to a lack of effectiveness or unacceptable toxicity, as comparedto the costs involved in the routine follow-up of patients on antiretroviraltreatment, from the Spanish National Health System perspective.Method: The use of resources (clinical tests, medical visits, and hospitalpharmacy visits) associated with following three profiles of patients infected with the human immunodeficiency virus (stable ones, those discontinuing an existing antiretroviral treatment and being switched to a newone due to a lack of effectiveness, and those discontinuing an existingantiretroviral treatment and being switched to a new one due to unacceptable toxicity) was identified, based on clinical practice guidelinesand the findings of a multidisciplinary expert panel (n = 5). The expertsagreed on the main adverse events leading to discontinuation, classifyingthem into gastrointestinal, renal, osseous, musculoskeletal, dermatological,hepatic, lipid profile-related, neuropsychiatric and sexual alterations. Unitcosts were identified from official healthcare costs databases. The cost (€, 2020) of following up each patient profile was estimated, excludingthe cost of the antiretroviral treatment itself, with a time horizon of twoyears.Results: The per-patient cost of following up stable patients over twoyears was estimated at €4,148 (tests: €2,293; visits: €1,855). Patientfollow-up after discontinuation of an existing antiretroviral treatment andinitiation of a different one due to a lack of effectiveness was estimatedat €5,434 (tests: €2,777; visits: €2,657). (AU)

Eyelash length in HIV-infected patients.

Acquired trichomegaly of the eyelashes in HIV-infected patients usually appears at the late stage of HIV infection. Eyelash length was measured in a series of 204 HIV patients, and no correlation with CD4 cell count, viral load, Centers for Disease Control and Prevention category, and AIDS case criteria was established. Our data support the finding that eyelash trichomegaly is currently uncommon in HIV-infected patients, perhaps because of antiretroviral therapy or an improvement in their immune situation.

Pegylated IFN-alpha2b plus ribavirin as therapy for chronic hepatitis C in HIV-infected patients.

BACKGROUND: Treatment of hepatitis C virus (HCV) has become a major challenge in HIV-infected individuals. No data exist on the efficacy and tolerability of pegylated IFN (peg-IFN) plus ribavirin in HIV-co-infected patients. METHODS: Subcutaneous peg-IFN (150 microg weekly during the first 12 weeks and 100 microg weekly thereafter) plus ribavirin (400 mg twice a day) was given to 68 HIV-infected patients with chronic hepatitis C, having CD4 cell counts greater than 300 cells/microl, plasma HIV-RNA less than 5000 copies/ml, and elevated aminotransferase levels. All were naive for IFN, and 73% were receiving antiretroviral drugs. RESULTS: Plasma HCV-RNA levels greater than 800 000 IU/ml were seen in 50%, and 35% carried HCV genotype 3. Adverse events leading to treatment discontinuation occurred in 10 patients (15%). One patient taking didanosine developed pancreatitis. Severe weight loss occurred in 70% of patients. Clearance of HCV-RNA at the end of therapy (6 months for HCV-3 and 12 months for HCV-1/4) occurred in 50% of patients (81% with HCV-3 versus 30% with HCV-1/4). As 30% relapsed, the overall sustained response rate was 35% (28% in the intent-to-treat analysis). The main predictors of response were infection with HCV-3 and low HCV load. CONCLUSION: Treatment with peg-IFN and ribavirin is relatively well-tolerated in HIV/HCV-co-infected patients, although new side-effects, including pancreatitis and severe weight loss, may result from the interaction of ribavirin with antiretroviral drugs. Overall, therapy provides cure to one third of patients, a rate significantly lower than that seen in HCV-monoinfected individuals. Given that relapses are common, extended periods of therapy should be investigated.

Total HCV core antigen assay. A new marker of HCV viremia and its application during treatment of chronic hepatitis C.

The present study assesses the clinical usefulness of the hepatitis C core antigen assay for monitoring of patients being treated for chronic hepatitis C virus (HCV) infection. Eighty-six serum samples were selected at random from 16 patients and levels of HCV RNA and HCV core antigen were determined simultaneously and in parallel to compare both techniques. The data obtained were compared by Pearson's correlation and the coefficients calculated by Fisher transformation and by calculating the difference and standard error. A good linear correlation was observed between both techniques. Maximum correlation, with significant difference, was found between patients infected with the 1a genotype and other genotypes. In conclusion, the HCV core antigen assay is useful for the diagnosis of early infection; however, its use for determining the exact timing of viral elimination during treatment is clearly unsuitable.