Current characteristics of patients with hepatitis C virus: results from an automated alert system.

Alert systems are proving to be useful to increase hepatitis C virus (HCV) diagnoses and facilitating access to antiviral treatment. Since 2020, our health department has had a fully automated alert system set up at the Microbiology Department. In this study, we present the results of the 2022-2023 period to assess the current characteristics of HCV diagnosed patients. In addition, we analyzed, through a comparison, whether a limitation that we noticed during the 2020-2021 period (whose results were published) is still present. This limitation consists of that 24.2% (34/134) of those candidates for antiviral treatment were not treated because they could not be located or refused treatment. During the 2022-2023 period, 188 new cases were diagnosed, and 75% (141/188) were treated. The comparison of both periods showed that in 2022-2023, the rate of treatment rejection by the patient was significantly lower (1.4% vs 14.5%, p < 0.05) and, therefore, the rate of antiviral treatment increased (75% vs 58.9%, p < 0.05). These results suggest that our alert system is useful and efficient for the diagnosis and treatment of HCV.

Reassessing HIV Detection Strategies: An Analysis of Opportunistic Screening vs. Indicator-Condition-Driven Diagnosis in Valencia, Spain.

Our study assessed the characteristics of people living with HIV (PLWH) detected via opportunistic screening in Valencia (Spain) to determine diagnoses potentially missed under a more restrictive, indicator-condition diagnostic strategy. We conducted a retrospective analysis of electronic health records of 97 PLWH diagnosed between April 2019 and August 2022. The main outcomes reported were patient CD4+ T cell count, known HIV risk factors at diagnosis, and missed opportunities for diagnosis, defined as the failure of a previously untested patient to undergo HIV testing despite attending previous visits to healthcare facilities prior to diagnosis. Successful linkage to care was achieved for 95.9% of diagnosed patients. Half of the PLWH were diagnosed late, while 47.8% did not meet the criteria for indicator-condition-driven HIV diagnosis at the time of their diagnosis. Additionally, 52.2% did not receive HIV testing despite an average of 5.1 ± 6.0 healthcare visits in the 12 months prior to diagnosis. Spaniards had more missed opportunities for diagnosis than foreigners (64% vs. 40%, p = 0.02). Depending solely on an indicator-condition-driven HIV diagnosis approach could result in 47.8% of cases being missed. Including "migrants" as a testing criterion could lower missed diagnoses to 25.3% but might create inequities in prevention access. In conclusion, our findings provide valuable insights to enhance HIV testing, early diagnosis, and linkage to care. While it is crucial to uphold the indicator-condition-driven HIV diagnosis as baseline practice, improving screening strategies will decrease late diagnoses and missed opportunities, thereby effectively contributing to end the epidemic.

Monkeypox whitlow: a novel presentation.

Monkeypox is a rare zoonotic disease with a progressive increase in cases among men who have sex with men (MSM) worldwide in recent months. New complications of this infection have been described. The aim of the study was to describe this new pattern of presentation of monkeypox at the level of the finger. We present the cases of three patients with monkeypox whitlow, a new clinical presentation of monkeypox. The patients were three MSM with ages ranging from 32 to 49 years. All three had involvement of the third finger of the dominant hand as well as skin lesions at other sites. Two of the three patients had severe inflammation in the digit and proximal arm and were treated with systemic corticosteroids with significant improvement. In two of the three cases we observed onychodystrophy as a complication. All patients reported sexual intercourse with previous digital-anal penetration with the affected finger, which may be the mode of transmission. Distinguishing features that need to be considered are discussed.

Clinical and Demographic Features of 49 Patients With Human Monkeypox Virus-Confirmed Infection in a Tertiary Care Center in Valencia, Spain: A Descriptive Study.

Monkeypox is a previously rare viral zoonosis affecting predominantly the African continent. Since May 2022, an increasing number of cases with no known epidemiologic link to Africa have been reported for the first time in the rest of the world. We described the epidemiologic and clinical characteristics of all patients attended at our center until August 9 with a confirmed diagnosis of monkeypox. Forty-nine patients were included. The mean age was 37.6 years. Ninety-eight percent of patients were male, 96% were men who have sex with men, and 4% were heterosexual. Thirty-one percent of patients had a history of human immunodeficiency virus infection. Ninety-six percent of patients declared a unprotected sexual relationship before the onset of symptoms, and 41% had a history of recent travel. Ninety-eight percent of patients presented with cutaneous involvement affecting the genital (59%), perianal (41%), and perioral (35%) regions. Systemic symptoms were present in 80% of the patients and included lymphadenopathies (71%), asthenia (65%), fever (65%), headache (37%), arthromyalgias (45%), pharyngitis (35%), proctitis (29%), and dysuria (6%). Coinfection by other sexually transmitted infections was detected in 20% of patients. The sensitivity values of polymerase chain reaction test for monkeypox in urethral, anal, and oropharyngeal exudates analyzed were 88%, 79%, and 68%, respectively. Complications included a myopericarditis that represented the only hospitalized patient, edema (8%) and bacterial superinfection (4%). No deaths were reported. The findings of this case series support the sexual contact as the main route of transmission of the disease and highlight some atypical clinical presentations not described in endemic cases.

Outcomes of an automated alert system from Microbiology to link diagnosis to treatment in patients with hepatitis C virus.

INTRODUCTION: simplification strategies for the care circuit of patients with hepatitis C virus (HCV) are key to achieve eradication. An electronic identification system was set up for HCV serology to link diagnosis to specialist management, aimed to reduce patient loss. MATERIAL AND METHODS: a retrospective, single-center study was performed in patients with HCV identified from 15/3/2020 to 15/12/2021, using an alert system from Microbiology that notified specialists of positive cases. The patient was contacted and appointed a Fibroscan® and viral load measurement, with antiviral therapy prescribed on the same day. Origin, public health data, patient location rate and antiviral therapy prescription were recorded. RESULTS: of 174 patients identified, 171 had positive viremia, with a mean age of 59.6 ± 15.9 years, 61.5 % were males and 81.2 % were Spanish nationals. Origin in the outpatient setting predominated (57.9 %, 99/171), particularly Primary Care (51/171), penitentiaries (21/171) and addiction units (14/171). Overall, 43.3 % (74/171) were aware of their diagnosis; 19.4 % (20/103) of patients had F3 fibrosis and 25.2 % (26/103) had F4 fibrosis. Also, 78.4 % (134/171) were deemed candidates for treatment. Of these, 74.6 % (100/134) were located and treatment was initiated, and all those who completed their treatment achieved a sustained viral response (96/96). This system managed 58.5 % (100/171) of the patients identified. The only association found between antiviral therapy and patient variables was comorbidities with being untreated (OR, 7.14; p ˂ 0.001). CONCLUSIONS: this alert system allows to minimize patient loss in the care circuit and provides high rates of treated patients.

Increasing and sustaining blood-borne virus screening in Spain and Portugal throughout the COVID-19 pandemic: a multi-center quality improvement intervention.

Background: Around 57,000 people in Spain and Portugal currently living with HIV or chronic hepatitis C are unaware of their infection. The COVID-19 pandemic severely disrupted screening efforts for these infections. We designed an intervention to increase and sustain opportunistic blood-borne virus (BBV) screening and linkage to care (SLTC) by implementing the TEST model. Methods: The Plan Do Study Act (PDSA) method of quality improvement (QI) was implemented in 8 healthcare organizations (HCOs), including four hospitals, two clusters of community health centers, and two community-based organizations (CBOs). Baseline assessment included a review of BBV SLTC practices, testing volume, and results 12 months before the intervention. Changes in BBV testing rates over time were measured before, during, and after the COVID-19 lockdowns in 2020. A mixed ANOVA model was used to analyze the possible effect on testing volumes among HCOs over the three study periods. Intervention: BBV testing was integrated into normal clinical flow in all HCOs using existing clinical infrastructure and staff. Electronic health record (EHR) systems were modified whenever possible to streamline screening processes, implement systemic institutional policy changes, and promote QI. Results: Two years after the launch of the intervention in screening practices, testing volumes increased by 116%, with formal healthcare settings recording larger increases than CBOs. The start of the COVID-19 lockdowns was accompanied by a global 60% decrease in testing in all HCOs. Screening emergency department patients or using EHR systems to automate screening showed the highest resilience and lowest reduction in testing. HCOs recovered 77% of their testing volume once the lockdowns were lifted, with CBOs making the fullest recovery. Globally, enhanced screening techniques enabled HCOs to diagnose a total of 1,860 individuals over the research period. Conclusions: Implementation of the TEST model enabled HCOs to increase and sustain BBV screening, even during COVID-19 lockdowns. Although improvement in screening was noted in all HCOs, additional work is needed to develop strong patient linkage to care models in challenging times, such as global pandemics.

HIV screening and linkage to care in a health department in Valencia, Spain: Lessons learned from a healthcare quality improvement project.

Spain's rate of new human immunodeficiency virus (HIV) diagnoses exceeds that of the European Economic Area average (8.6 vs 5.6:100,000 in 2018). The country has failed to meet the first of United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets for HIV control by 2020, with 87.0% of people living with HIV knowing their status, and late presentation rates of 47.6% and 51.5% country-wide and in the Valencian autonomous community, respectively. Advancing screening and linkage to care (SLTC) practices is necessary to effectively control the epidemic. The Valencia Viral Screening (CRIVALVIR) project adopted the TEST model for opportunistic and systematic HIV SLTC in individuals aged 18 to 80 who required blood work for any purpose, as of February 2019. SLTC was integrated into routine clinical workflow across primary care centers serving a population of 360,000 people in Valencia, Spain. Our project successfully upscaled total HIV testing by 194% to over 32,000 patients tested in 14 months. We found an overall prevalence of 0.13% (0.08-0.21) among those screened per protocol (n = 13,061), with foreign-born citizens presenting a 12.5 times significantly higher likelihood of acquiring HIV (95% confidence interval 4.63-33.96, P < .0001). We improved late presentation by 18.2 percentage points and prevented an estimated 58 to 70 new secondary infections. HIV screening of the general population in primary care is an effective strategy for achieving timely diagnosis and preventing new infections. Opportunistic, systematic, opt-out approaches are essential to control the HIV epidemic.

One-step diagnosis strategy together with multidisciplinary telematics referral perform an effective approach for identifying and treating patients with active Hepatitis C infection.

INTRODUCTION AND OBJECTIVES: Implementation of a one-step strategy for diagnosis of active Hepatitis C virus (HCV) infection would encourage the early diagnosis and reduce the time to access antiviral treatments. The aim of this study was to evaluate the impact of a HCV one-step diagnosis compared to the traditional two-step protocol in terms of the time required for patients to be seen by specialists and the time taken to start antiviral treatment. MATERIAL AND METHODS: A comparative study was carried out to assess two diagnostic algorithms (one-step and two-step) for active HCV infection. Serological markers were quantified using the same serum sample to determine both anti-HCV antibodies (HCV-Ab) and HCV core antigen (HCV-cAg) by Architect i2000 SR kit. In this period, a multidisciplinary procedure was started for telematics referral of viremic patients. RESULTS: One-step approach reduced the time required for patient HCV diagnosis, referral to a specialist, access to treatment, and eliminated the loss of patients to follow-up. Significant differences were observed between one-step and two-step diagnosis methods in the time required for patients to be seen by a specialist (18 days [Interquartile range (IQR) = 14-42] versus 107 days [IQR = 62-148]) and for the initiation of treatment (54 days [IQR = 43-75] versus 200 days [IQR = 116-388]), mainly for patients with advanced fibrosis (35 days [IQR = 116-388] versus 126 days [IQR = 152-366]). CONCLUSIONS: Use of HCV-cAg has proven to be a useful tool for screening patients with active hepatitis C. The development of a multidisciplinary protocol for the communication of results improved the efficiency of the care process.

Abnormal liver chemistry constitutes an independent prognostic factor of less favorable clinical course in patients with COVID-19.

INTRODUCTION: abnormal liver biochemistry (ALB) is correlated with increased clinical involvement or severity in COVID-19, but its prognostic implications have not been studied extensively. The aim of this study was to determine whether ALB is a risk factor for unfavorable clinical outcome and involvement. MATERIALS AND METHODS: a retrospective, single-center study in confirmed COVID-19 cases. Patients with pharmacological hepatotoxicity or liver diseases were excluded. ALB was defined as any elevation of total bilirubin, AST, ALT, alkaline phosphatase, and/or GGT above the upper limit of normal. First, an assessment was made of the correlation between ALB and need for hospitalization. This was followed by an assessment of the correlation of ALB in hospitalized patients with demographic variables, comorbidities, and treatment for COVID-19, and with clinical involvement and outcome. The statistical analysis was performed using an age-adjusted multiple logistic regression with a p-value < 0.05. RESULTS: of 1,277 confirmed cases, 346 required hospitalization and 302 were included. The prevalence of ALB was higher in hospitalized patients compared to non-hospitalized patients (60.9 % vs. 10.3 %, p ˂ 0.001). Among hospitalized patients, there was no correlation between ALB and demographic variables, comorbidities, or treatment for COVID-19, except for low molecular weight heparin. There was a significant correlation between ALB and moderate/severe COVID-19 involvement and between unfavorable clinical outcomes and elevated total bilirubin. The period of greatest clinical worsening and deterioration of liver biochemistry parameters occurred during the first seven days. There was a significant correlation of ALB with longer hospital stay and admission to the intensive care unit, but this did not imply increased mortality. CONCLUSIONS: ALB correlates with greater clinical involvement and worse clinical outcomes in hospitalized patients with COVID-19.

Implementation of pre-exposure prophylaxis programme in Spain. Feasibility of four different delivery models.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is an effective and cost-effective strategy for HIV prevention. Spain carried out an implementation study in order to assess the feasibility of implementing PrEP programmes within its heterogeneous health system. METHODS: Observational longitudinal study conducted on four different types of health-care setting: a community centre (CC), a sexually transmitted infections clinic (STIC), a hospital-based HIV unit (HBHIVU) and a hospital-based STI unit (HBSTIU). We recruited gay, bisexual and other men who have sex with men (GBSM) and transgender women at risk of HIV infections, gave them PrEP and monitored clinical, behavioural PrEP-related and satisfaction information for 52 weeks. We collected perceptions on PrEP implementation feasibility from health-care professionals participating in the study. RESULTS: A total of 321 participants were recruited, with 99.1% being GBMSM. Overall retention was 87.2% and it was highest at the CC (92.6%). Condom use decreased during the study period, while STIs did not increase consistently. The percentage of people who did not miss any doses of PrEP during the previous week remained at over 93%. No HIV seroconversions occurred. We observed overall decreases in GHB (32.5% to 21.8%), cocaine (27.5% to 21.4%), MDMA (25.7% to 14.3%), speed (11.4% to 5.7%) and mephedrone use (10.7% to 5.0%). The overall participant satisfaction with PrEP was 98.6%. Health-care professionals' perceptions of PrEP feasibility were positive, except for the lack of personnel. CONCLUSIONS: PrEP implementation is feasible in four types of health-care settings. Local specificities have to be taken into consideration while implementing PrEP.

Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study.

BACKGROUND: Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing. METHODS: ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing. FINDINGS: Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34-50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI -0·6-2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred. INTERPRETATION: The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1. FUNDING: ViiV Healthcare and Janssen.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

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 (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). 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 (P = 0.16). 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 (P = 0.006). 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; P = 0.12]. 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.

Executive summary: Consensus document of GEHEP of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), along with SOCIDROGALCOHOL, SEPD and SOMAPA on hepatitis C virus infection management in drug users / Resumen ejecutivo: Documento de consenso de GEHEP, perteneciente a la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), junto a SOCIDROGALCOHOL, SEPD y SOMAPA, sobre el manejo de la infección por virus de la hepatitis C en usuarios de drogas

The micro-elimination of HCV infection in drug users (DU) in our area is a priority in order to achieve the overall elimination of this disease. Coordinated action between specialists in addiction treatment, microbiologists and physicians who treat HCV infection is required to implement infection screening, to achieve universal access to treatment and to prevent new infections and reinfections. The objective of this document was to come to a consensus on the screening, hospital referral, treatment, follow-up and prevention of HCV infection in DU by an expert panel from GEHEP/SEIMC and three scientific societies of addiction treating physicians: SEPD, SOCIDROGALCOHOL and SOMAPA

La microeliminación de la infección por VHC en pacientes usuarios de drogas (UD) es una prioridad para lograr la eliminación global de esta enfermedad. Se requiere una acción coordinada de especialistas en el tratamiento de adicciones, microbiólogos y médicos que tratan la infección por VHC para realizar el cribado de los pacientes, garantizar el acceso al tratamiento y prevenir nuevas infecciones y reinfecciones. El objetivo de este documento fue consensuar las medidas de cribado, envío a unidades hospitalarias, tratamiento, seguimiento y prevención de la infección por VHC en UD, por parte de un panel de expertos de GEHEP/SEIMC y 3 sociedades científicas implicadas en el tratamiento de las adicciones: SEPD, SOCIDROGALCOHOL y SOMAPA

Executive summary: Consensus document of the diagnosis, management and prevention of infection with the hepatitis E virus: Study Group for Viral Hepatitis (GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) / Resumen ejecutivo: Documento de consenso del Grupo de Estudio de las Hepatitis Víricas perteneciente a la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica sobre el diagnóstico, manejo y prevención de la infección por el virus de la hepatitis E

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

La infección por el virus de la hepatitis E (VHE) es una de las principales causas de hepatitis aguda tanto en países desarrollados como en vías de desarrollo, situándose como una enfermedad infecciosa de alta prevalencia e incidencia en Europa. La infección por el VHE tiene mayor impacto clínico en poblaciones especialmente vulnerables, como pacientes inmunodeprimidos, mujeres embarazadas y pacientes con hepatopatía base. Por todo ello, desde el Grupo de Estudio de las Hepatitis Víricas (GeHEP) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) se considera de gran relevancia la elaboración de un Documento de Consenso que sirva de ayuda en la toma de decisiones sobre el diagnóstico, manejo clínico-terapéutico y la prevención de la infección por el VHE

Executive summary: Consensus document of GEHEP of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), along with SOCIDROGALCOHOL, SEPD and SOMAPA on hepatitis C virus infection management in drug users.

The micro-elimination of HCV infection in drug users (DU) in our area is a priority in order to achieve the overall elimination of this disease. Coordinated action between specialists in addiction treatment, microbiologists and physicians who treat HCV infection is required to implement infection screening, to achieve universal access to treatment and to prevent new infections and reinfections. The objective of this document was to come to a consensus on the screening, hospital referral, treatment, follow-up and prevention of HCV infection in DU by an expert panel from GEHEP/SEIMC and three scientific societies of addiction treating physicians: SEPD, SOCIDROGALCOHOL and SOMAPA.

Executive summary: Consensus document of the diagnosis, management and prevention of infection with the hepatitis E virus: Study Group for Viral Hepatitis (GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

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.

Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort.

Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.

Rapid Initiation of Antiretroviral Therapy after HIV Diagnosis.

Roughly, 38 million people are living with HIV worldwide. Despite the success of antiretroviral therapy (ART) for suppressing virus replication and restore immunity in infected persons, the HIV epidemics are not controlled globally. Each year 1.8 million new HIV infections occur. This rate has declined only slightly during the past decade, despite huge efforts for expanding ART coverage, pre- and post-exposure prophylaxis, and stopping vertical transmission. To achieve the United Nations Programme on HIV/AIDS goals of 95-95-95 by 2030, renewed efforts and innovative strategies must be undertaken. The source of most new HIV infections is people unaware of their HIV-positive status and/or not linked to care. Thus, efforts for unveiling HIV positives and, especially, rapid initiation of ART and retention in care would be the most effective interventions for halting HIV spreading globally. In certain settings, access to point-of-care diagnostic tests and immediate start of ART (even the same day) must be implemented at large scale. Selection of the most convenient ART to be prescribed empirically is an important caveat to minimize the risks of treatment failure. Ideally, it must be easy to take, coformulated as single-tablet regimen (STR), well tolerated, with no requests for prior human leukocyte antigen testing, depict few drug interactions, keep activity against transmitted drug-resistant viruses, remain efficacious in patients with elevated HIV-RNA, and/or low CD4 counts, and when present, suppress hepatitis B coinfection. At this time, the coformulation of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide (Symtuza®) is the only regimen that has been evaluated in a Phase 3 trial as "test-and-treat" strategy. Results at 48 weeks in the DIAMOND study are reassuring, as more than 90% of individuals achieve undetectable viremia.

High efficacy of resistance-guided retreatment of HCV patients failing NS5A inhibitors in the real world.

BACKGROUND & AIMS: Most hepatitis C virus (HCV)-infected patients failing NS5A inhibitors develop resistance-associated substitutions (RASs). Here we report the use of resistance-guided retreatment of patients who failed prior NS5A inhibitor-containing regimens in the GEHEP-004 cohort. This is the largest direct-acting antiviral (DAA)-resistance cohort study conducted in Spain. We aim to provide indications on how to use resistance information in settings where sofosbuvir/velpatasvir/voxilaprevir may not be available. METHODS: GEHEP-004 is a prospective multicenter cohort enrolling HCV-infected patients treated with interferon (IFN)-free DAA regimens. Prior to retreatment, population-based sequencing of HCV NS3, NS5A and NS5B genes was performed. After receiving a comprehensive resistance interpretation report, the retreatment regimen was chosen and the sustained virological response (SVR) at 12 weeks after treatment completion (SVR12) was recorded. RESULTS: A total of 342 patients experiencing virological failure after treatment with sofosbuvir/ledipasvir±ribavirin (54%), sofosbuvir/daclatasvir±ribavirin (23%), or paritaprevir-ritonavir/ombitasvir±dasabuvir±ribavirin (20%) were studied. After a resistance report, 186 patients were retreated. An SVR12 was achieved for 88.1% of the patients who failed after sofosbuvir/ledipasvir±ribavirin, 83.3% of the patients who failed after sofosbuvir/daclatasvir±ribavirin, 93.7% of the patients who failed after paritaprevir-ritonavir+ombitasvir±dasabuvir±ribavirin. CONCLUSIONS: In our study, we show how resistance-guided retreatment in conjunction with an interpreted report allows patients to achieve SVR rates close to 90%. We hypothesize that SVR rates may even be improved if resistance data are discussed between experienced virologists and treating clinicians. We believe that our data may be relevant for countries where the access to new DAA combination regimens is limited. LAY SUMMARY: Hepatitis C infection can be cured with currently available antiviral agents. Only a small proportion of patients experience treatment failure, however, in absolute numbers, a high number of patients may require retreatment. Highly effective combinations of antivirals are also available for retreatment. However, these antivirals might not be available in resource-limited settings. Herein, we show how, by analyzing the cause of resistance, retreatment efficacy with old drugs can get very close to the efficacy of new drug combinations.

Hepatitis C virus infection and new treatment strategies. / Infección por el virus de la hepatitis C y nuevas estrategias de tratamiento.

Hepatitis C is a major public health problem worldwide. This disease is caused by the hepatitis C virus, which is characterised by its genetic diversity. The infection is usually asymptomatic. However, between 60% and 80% of HCV-infected individuals will progress to chronic hepatitis, 20% to liver cirrhosis in the medium-to long-term and, each year, between 1% and 4% of these patients with cirrhosis will develop hepatocellular carcinoma (HCC). A Spanish consensus document has recently been drafted to diagnose hepatitis C in a single step, consisting of active investigation (antibodies and viremia) in a single sample, which according to the experts, would reduce the time to access treatment and avoid tracking losses. To definitively change the hepatitis C treatment paradigm, direct-acting antiviral drugs (DAAs) have been approved, whose development has been based on achieving cure rates close to 100% regardless of the genotype of the virus, ie, pangenotypes, with good tolerance and bioavailability. These drugs have constituted a real therapeutic revolution. Supplement information: This article is part of a supplement entitled «SEIMC External Quality Control Programme. Year 2016¼, which is sponsored by Roche, Vircell Microbiologists, Abbott Molecular and Francisco Soria Melguizo, S.A. © 2019 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosasy Microbiología Clínica. All rights reserved.