Long or complicated mpox in patients with uncontrolled HIV infection.

To date, former research about the impact of HIV infection on mpox poor outcomes is still limited and controversial. Therefore, the aim of this study was to assess the impact of HIV on the clinical course of mpox, in a large population of patients from Spain. Nationwide case-series study. Patients from 18 Spanish hospitals, with PCR-confirmed mpox from April 27, 2022 to June 30, 2023 were included in this study. The main outcome was the development of long or complicated (LC) mpox, defined as: (i) duration of the clinical course ≥ 28 days, or; (ii) disseminated disease, or: (iii) emergence of severe complications. One thousand eight hundred twenty-three individuals were included. Seven hundred eighty-six (43%) were people living with HIV (PLWH), of whom 11 (1%) had a CD4 cell count < 200 cells/mm3 and 33 (3%) <350 cells/mm3 . HIV viral load ≥ 1000 cp/mL was found in 27 (3%) PLWH, none of them were on effective ART. Fifteen (60%) PLWH with HIV-RNA ≥ 1000 cp/mL showed LC versus 182 (29%) PLWH with plasma HIV-RNA load < 1000 copies/mL and 192 (24%) individuals without HIV infection (p < 0.001). In multivariate analysis, adjusted by age, sex, CD4 cell counts and HIV viral load at the time of mpox, only plasma HIV-RNA ≥ 1000 cp/mL was associated with a greater risk of developing LC mpox [adjusted OR = 4.06 (95% confidence interval 1.57-10.51), p = 0.004]. PLWH with uncontrolled HIV infection, due to lack of ART, are at a greater risk of developing LC mpox. Efforts should be made to ensure HIV testing is carried out in patients with mpox and to start ART without delay in those tested positive.

Response to glecaprevir/pibrentasvir in HIV/HCV-coinfected patients in clinical practice.

OBJECTIVES: HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials. METHODS: The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts. RESULTS: Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (P = 1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use. CONCLUSIONS: G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.

Proceso de atención en enfermería basado en mapa de cuidados en persona mayor reintervenida quirúrgicamente por reemplazo de cadera. Reporte de un caso

El proceso de atención en enfermería (PAE) es un método sistemático y organizado que requiere de un entrenamiento específico, tener conocimientos y habilidades prácticas que proporcionan las herramientas para brindar cuidado abordando las dimensiones de forma holística a partir de una interacción directa con el paciente, la familia y el entorno social. Se presenta el PAE de una persona mayor, femenina, de 65 años de edad, con pluripatologías: síndrome purpúrico, monoparesia de miembro inferior derecho y síndrome convulsivo, reintervenida quirúrgicamente de un reemplazo de cadera derecha. Se plantea el PAE y sus cinco etapas: valoración, diagnóstico, planeación, ejecución y evaluación; siguiendo la valoración por dominios. El plan de cuidados se realiza con el enfoque de mapa de cuidados en la situación quirúrgica, diagnóstico NANDA International, lnc. La evaluación de intervenciones NIC (Nursing Interventions Classification) y resultados NOC (Nursing Outcomes Classification).

The Nursing Care Process (NCP) is a systematic and organized method that requires specific training, knowledge and practical skills that provide the tools needed to provide care by addressing the dimensions holistically from direct interaction with the patient, the family and social environment. Te NCP of a 65-year-old female elderly person with multiple pathologies; purpuric syndrome, right lower limb monoparesis and convulsive syndrome, who underwent surgery for a right hip replacement is presented. The Nursing Care Process (NCP) and its five stages are proposed: assessment, diagnosis, Outcomes/ Planning, Implementation and evaluation; following the valuation by domains. The care plan was carried out with the care map approach, NANDA Internacional Inc. Te evaluation of NIC (Nursing Interventions Classification) interventions and NOC (Nursing Outcomes Classification) results.

Weight changes after first-line antiretroviral initiation in a cohort of HIV-positive patients in Southern Spain (CAPOTA study).

BACKGROUND: Obesity among persons living with HIV (PLWH) has increased and weight gain after antiretroviral therapy (ART) can lead to metabolic disorders and impact survival. Our objective was to analyze weight and metabolic changes in HIV näive patients after 48 weeks of ART. METHODS: Observational, retrospective, multicentered cohort study comprising naïve-patients who started tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) or abacavir/lamivudine/dolutegravir (ABC/3TC/DTG), with no change in treatment for 48 weeks. Clinical and metabolic parameters were collected at baseline and week-48. Statistical program used was SPSS 21.0.0. RESULTS: The study included 329 participants from 6 hospitals. Participants were 89% male and 10% had AIDS diagnosis. Median age was 35 (IQR 27-43) years. Median baseline CD4 count was 417 (IQR 250-569) cell/mm3 and HIV viral load 4.65 (IQR 4.21-5.18) log10 copies/ml. Baseline median weight was 70 (IQR 62-79) kg, body mass index 23.4 (IQR 21.2-26.0) kg/m2; 22.7% overweight and 6.4% obese. ART regimens: ABC/3TC/DTG (196), TAF/FTC/EVG/c (133). Baseline characteristics were similar in both ART groups. Average weight gain at week-48 was 2.9 (SD 5.5) kg (p < 0.0001) with no differences between both groups. There was an increase in obesity (6.4%-8%; p < 0.003) and overweight (22.7%-28.9%; p < 0.0001). Weight increase was associated with AIDS: OR 3.05 (95%; CI 1.009-9.22), p = 0.048; and lower baseline weight: OR 1.032 (95% CI 1.009-1.05), p = 0.006. CONCLUSIONS: After ART initiation patients gain weight regardless of the regimen they take. Weight gain is associated with AIDS and the use of TAF/FTC/EVG/c.

High efficacy of glecaprevir/pibrentasvir for HCV-infected individuals with active drug use.

OBJECTIVES: Real world data on glecaprevir/pibrentasvir (G/P) among active drug users are scarce. We evaluated the sustained virological response (SVR) rates of G/P among individuals with and without active drug use in routine clinical practice. METHODS: Two ongoing prospective multicenter cohorts of individuals starting G/P were analyzed. Overall SVR intention-to-treat (ITT), discontinuations due to adverse effects and dropouts were evaluated. Results in patients with active, past and without active drug use were compared. RESULTS: Overall, 644 individuals started G/P and have reached the date of SVR evaluation. Of them, 613 (95.2%) individuals achieved SVR. There were two (0.3%) relapses, one (0.2%) discontinuation due to side effects and 35 (5.4%) dropouts. SVR rates for patients with active drug use, past drug use and those who never used drugs were 85.4%(n/N = 70/82), 96.1%(n/N = 320/333) and 97.4%(n/N = 223/229) respectively (p < 0.001). After adjustment by sex, age, HCV genotype and opioid agonist therapy, active drug use was the only factor independently associated with SVR (ITT) [adjusted OR (95%confidence interval): 0.29(0.09-0.99),p = 0.048]. CONCLUSIONS: Active drug use was independently associated with lower SVR rates to G/P, mainly due to voluntary dropout. G/P could be particularly beneficial in this scenario but specific strategies designed to increase the retention in care are needed.

Síndrome de burnout en el personal de enfermería en hospitales del departamento del Atlántico / Burnout syndrome in the nursing personal in health care institutions of the Atlantic department

RESUMEN Objetivo Determinar la prevalencia del síndrome de burnout en el personal de enfermería en hospitales del Departamento del Atlántico (Colombia). Materiales y Métodos Se realizó un estudio cuantitativo, descriptivo transversal, en 117 profesionales y 229 auxiliares de enfermería de cuatro hospitales del Departamento del Atlántico (Colombia), dos públicos y dos privados. Se empleó una encuesta anónima con datos sociodemográficos y la escala de Maslach. Resultados La prevalencia global del síndrome de burnout o desgaste profesional fue de 65%. En profesionales de enfermería, fue de 63,2% y en auxiliares de enfermería, de 65,9%. El 13,3% de los participantes presentó un grado elevado de burnout para el cansancio emocional; el 9,2%, para la despersonalización; y el 62,7% obtuvo puntuaciones bajas para la realización personal. En los profesionales de enfermería, el 12,7% obtuvo una puntuación alta para cansancio emocional; 7,4% para despersonalización, y 64,2% obtuvo puntuaciones bajas para la realización personal. Por su parte, en los auxiliares de enfermería el comportamiento en algunas subescalas fue muy similar; el 14,5% obtuvo una puntuación alta para cansancio emocional; 12,8%, para despersonalización y 59,8% obtuvo puntuaciones bajas para la realización personal. Conclusiones La presencia del síndrome de burnout en la población estudiada es alta. Es similar tanto en enfermeros como en auxiliares de enfermería. La dimensión más afectada fue la realización personal en ambos grupos estudiados, lo cual corresponde a sentimientos altos del "quemado".

ABSTRACT Objective To determine the prevalence of burnout syndrome in the nursing staff in four hospitals located in the State of Atlántico (Colombia). Material and Methods A descriptive cross-sectional study was conducted and included as participants 117 nursing professionals and 229 nursing auxiliaries from four hospitals located in the State of Atlantico (Colombia), two public and two privates. An anonymous self-study survey was used on sociodemographic, labor data and Maslach Scale. Results The overall prevalence of Burnout Syndrome or professional burnout was 65%. In nursing professionals it was 63,2% and in nursing auxiliaries 65,9%. At least 13,3% of the participants had a high degree of Burnout from emotional exhaustion, 9.2% for depersonalization, and 62,7% had low scores for personal fulfillment. In nursing professionals, 12,7% had a high score for emotional exhaustion, 7,4% for depersonalization, and 64,2% obtained low scores for personal fulfillment. On the other hand, in nursing auxiliaries the behavior in some subscales was very similar, 14,5% had a high score for emotional exhaustion, 12,8% for depersonalization and 59,8% had low scores for personal fulfillment. Conclusions The presence of burnout syndrome is high in the studied population, it is similar in both, nurses and nursing auxiliaries. The most affected dimension was the personal fulfillment in both groups, which corresponds to high feelings of the "burned".

A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure.

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes.

Kinetics of emergence of liver complications in hepatitis C virus infected patients and advanced fibrosis, with and without HIV-coinfection, after sustained virological response.

OBJECTIVE: There is scarce available evidence on the distribution over time of liver complications emergence in hepatitis C virus (HCV)-infected patients who achieve sustained virological response (SVR) with direct-acting antiviral (DAA)-based therapy. Therefore, we aimed at describing the kinetics of liver-related events appearance in this setting. DESIGN: A multicentric prospective cohort study. METHODS: HCV-monoinfected and HIV/HCV-coinfected patients from GEHEP-011 cohort, whose inclusion criteria were had achieved SVR with DAA-based therapy; liver stiffness prior to starting treatment at least 9.5 kPa; and available liver stiffness measurement at SVR. SVR was considered as the baseline time-point. RESULTS: One thousand and thirty-five patients were included, 664 (64%) coinfected with HIV. Before DAA-based therapy, 63 (6.1%) individuals showed decompensated cirrhosis. After SVR, 51 (4.9%) patients developed liver complications. Median (Q1-Q3) time to the emergence of hepatic events was hepatic encephalopathy 11 (7-24) months, ascites 14 (6-29) months, hepatocellular carcinoma (HCC) 17 (11-42) months and portal hypertension gastrointestinal bleeding (PHGB) 28 (22-38) months (P = 0.152). We define two profiles of liver complications: those emerging earlier (encephalopathy and ascites) and, those occurring continuously during the follow-up (HCC, PHGB) [median (Q1-Q3) time to emergence 12.7 (6.6-28.2) months vs. 25.4 (12.5-41.53) months, respectively (P = 0.026)]. CONCLUSION: The vast majority of HCV-infected patients who develop liver complications after reaching SVR with DAA do it within 3 years after SVR time-point. Specifically, hepatic encephalopathy and ascites do not usually emerge after this period. Conversely, HCC and PHGB may occur in longer term. It is critical to identify patients at risk of developing hepatic events to continue performing surveillance for them.

Impact of recent drug use on the efficacy of elbasvir/grazoprevir for HCV-infected people on opioid agonist therapy.

Elbasvir/grazoprevir (EBR/GZR) use in drug users on opiate agonist therapy (OAT) is supported by the C-EDGE Co-STAR trial. SVR rates in this study were within those found in the rest of patients included by the EBR/GZR development programme. In clinical practice, however, efficacy could theoretically be lower. Thus, we aimed at evaluating the SVR rates of EBR/GZR among people who injected drugs (PWID) with and without OAT in clinical practice. Patients starting EBR/GZR included in the HEPAVIR-DAA (NCT02057003), recruiting HIV/HCV-coinfected patients or the GEHEP-MONO (NCT02333292), including HCV-monoinfected individuals, prospective cohorts were analysed. Overall SVR12 (ITT), discontinuations due to adverse effects and drop-outs were evaluated. The same analysis was carried out for PWID with and without OAT. 336 patients had started EBR/GZR and reached the SVR12 evaluation date. 318 [95%, 95% confidence interval (95% CI): 92%-98%] patients achieved SVR12. SVR12 was 97% (95% CI: 93%-99%, n/N = 141/145) among people who never used injecting drugs, 94% (95% CI: 88%-97%, n/N = 117/125) among PWIDs without OAT and 91% (95% CI: 81%-97%, n/N = 60/66) among PWIDs with OAT (p = 0.134). Five (1.5%) patients showed relapses, and two (0.6%) individuals showed viral breakthrough. The SVR12 rate for recent drug users was 69% (n/N = 18/26) compared with 97% (n/N = 276/284) for individuals without recent drug use (in the prior year) (p < 0.001). Among recent drug users, three (12%) showed relapses, and five (19%) were lost-to-follow-up. The SVR rates achieved with EBR/GZR were high in real-world conditions of use. However, PWID with recent drug use reach suboptimal response rates with EBR/GZR.

Clinical, Immunological, and Virological Outcomes Among Youths With Perinatal HIV After Transition to Adult Units in Spain From 1997 to 2016.

BACKGROUND: Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV. METHODS: Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods. RESULTS: Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range: 16.3-18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range: 4.6-9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition. CONCLUSIONS: After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.

Liver Stiffness-Based Strategies Predict Absence of Variceal Bleeding in Cirrhotic Hepatitis C Virus-Infected Patients With and Without Human Immunodeficiency Virus Coinfection After Sustained Virological Response.

BACKGROUND: In the setting of hepatitis C virus (HCV) active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can be safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predicting this outcome in HCV-infected patients with cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, are very limited. METHODS: This was a multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they had (1) SVR with direct-acting antiviral-based therapy; (2) LS ≥9.5 kPa previous to treatment; and (3) LS measurement at the SVR time-point ≥14 kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI, and HIV cirrhosis criteria, at the time of SVR, was evaluated. Missed VB episodes, negative predictive values (NPVs), and number of spared UGEs were specifically assessed. RESULTS: Four hundred thirty-five patients were included, 284 (65%) coinfected with HIV. Seven (1.6%) patients developed a first episode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (95% confidence interval [CI], 97.1%-100%), 100% (95% CI 97.8%-100%), and 100% (95% CI 98%-100%) while sparing 45%, 39%, and 44% of UGEs, respectively. When considering HIV coinfection, the performance of the 3 criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals. CONCLUSIONS: After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.

Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy.

BACKGROUND & AIMS: There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. METHODS: Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. RESULTS: Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. CONCLUSIONS: VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. LAY SUMMARY: The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).

What is needed to achieve HCV microelimination among HIV-infected populations in Andalusia, Spain: a modeling analysis.

BACKGROUND: Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015-2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling. METHODS: A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall. RESULTS: Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030. CONCLUSION: Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.

"It made me more confident that I have it under control": Patient and provider perspectives on moving to a two-drug ART regimen in the United States and Spain.

BACKGROUND: Two-drug regimens (2DR) to treat HIV infection have the potential to reduce long-term toxicity and increase therapeutic options for people living with HIV (PLHIV). Prior phase III trials, SWORD-1 and SWORD-2, as well as GEMINI-1 and GEMINI-2, have demonstrated that a dolutegravir-based 2DR is as effective as three- or four-drug regimens among virologically suppressed patients. Limited information exists, however, on patient and provider experiences with 2DR to inform roll-out and integration into routine clinical care. METHODS: We conducted 39 in-depth interviews with PLHIV currently on 2DR in the context of routine care and 8 of their clinical care providers in the United States (U.S.) and Spain. Participants included 33 male and 6 female PLHIV and 8 providers. Interview topics explored perceptions of and experiences with 2DR compared to prior anti-retroviral regimens (ARVs), side effects, patient satisfaction, and clinical performance. Interviews were audio-recorded, transcribed and analyzed using thematic content analysis. RESULTS: Participants viewed 2DR as a significant and positive advance, in terms of its ability to effectively treat HIV with reduced toxicity and essentially no reported side effects. Patients noted the central role providers played in the decision to switch to a 2DR regimen and, among U.S. participants, the importance of insurance coverage making this preferred option feasible. Patients and providers agreed that a 2DR regimen would be appropriate for any PLHIV regardless of whether they were treatment naïve or had significant experience with ARVs. CONCLUSIONS: Participants' experiences with a 2DR regimen were positive with no participants, reporting side effects and all reporting continued viral suppression. Providers valued the reduced toxicity offered by 2DR and served as the primary gateway to a transition to 2DR for patients in both settings. This study provides a foundation for further research on the transition to 2DR regimens in other populations and contexts including low- and middle-income settings.

Using machine learning methods to determine a typology of patients with HIV-HCV infection to be treated with antivirals.

Several European countries have established criteria for prioritising initiation of treatment in patients infected with the hepatitis C virus (HCV) by grouping patients according to clinical characteristics. Based on neural network techniques, our objective was to identify those factors for HIV/HCV co-infected patients (to which clinicians have given careful consideration before treatment uptake) that have not being included among the prioritisation criteria. This study was based on the Spanish HERACLES cohort (NCT02511496) (April-September 2015, 2940 patients) and involved application of different neural network models with different basis functions (product-unit, sigmoid unit and radial basis function neural networks) for automatic classification of patients for treatment. An evolutionary algorithm was used to determine the architecture and estimate the coefficients of the model. This machine learning methodology found that radial basis neural networks provided a very simple model in terms of the number of patient characteristics to be considered by the classifier (in this case, six), returning a good overall classification accuracy of 0.767 and a minimum sensitivity (for the classification of the minority class, untreated patients) of 0.550. Finally, the area under the ROC curve was 0.802, which proved to be exceptional. The parsimony of the model makes it especially attractive, using just eight connections. The independent variable "recent PWID" is compulsory due to its importance. The simplicity of the model means that it is possible to analyse the relationship between patient characteristics and the probability of belonging to the treated group.

Evaluation of hepatitis C viral RNA persistence in HIV-infected patients with long-term sustained virological response by droplet digital PCR.

Several studies have reported the persistence of HCV RNA in liver and/or peripheral blood mononuclear cells (PBMCs) in spite of undetectable viremia in patients who have achieved sustained virological response (SVR). This event, defined as occult HCV infection, remains controversial and low titers of persistent virus may be underestimated because it has not yet been analyzed by a highly sensitive test such as droplet digital PCR (ddPCR). This method provides an alternate ultra-sensitive detection technique for very low numbers of copies of viral RNA or DNA. The aim of this study was to evaluate the persistence of HCV in HIV-coinfected patients with long-term SVR using ddPCR. For each patient, the presence of HCV RNA in serum and PBMCs at baseline was determined by nested RT-ddPCR. Patients with HCV RNA in PBMCs at baseline were followed until the end of the study. One hundred and twenty-three patients were analyzed for persistence of HCV RNA in serum and PBMCs. Persistence of HCV was not found in serum in any patient. HCV RNA was detected in PBMCs in one patient (0.81%; 95% CI: 0.04-3.94) and resolved spontaneously during follow-up. Persistence of HCV RNA in PBMCs is not a common event in HIV/HCV co-infected patients with long-term SVR evaluated by RT-ddPCR.

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.

A genome-wide association study on low susceptibility to hepatitis C virus infection (GEHEP012 study).

BACKGROUND: A low proportion of individuals repeatedly exposed to the hepatitis C virus (HCV) remain uninfected. This condition could have a genetic basis but it is not known whether or not it is mainly driven by a high-penetrance common allele. OBJECTIVE: To explore whether low susceptibility to HCV infection is mainly driven by a high-penetrance common allele. METHODS: In this genome-wide association study (GWAS), a total of 804 HCV-seropositive individuals and 27 high-risk HCV-seronegative (HRSN) subjects were included. Plink and Magma software were used to carry out single nucleotide polymorphism (SNP)-based and gene-based association analyses respectively. RESULTS: No SNP nor any gene was associated with low susceptibility to HCV infection after multiple testing correction. However, SNPs previously associated with this trait and allocated within the LDLR gene, rs5925 and rs688, were also associated with this condition in our study under a dominant model (24 out of 27 [88.9%] rs5925-C carriers in the HRSN group vs 560 of 804 [69.6%] rs5925-C carriers in the HCV-seropositive group, P = 0.031, odds ratio [OR] = 3.48; 95% confidence interval [CI] = 1.04-11.58; and 24 out of 27 [88.9%] rs688-T carriers in the HRSN group vs 556 of 804 [69.1%] rs688-T carriers in the HCV-seropositive group, P = 0.028, OR = 3.57, 95% CI = 1.65-11.96). CONCLUSIONS: Low susceptibility to HCV infection does not seem to be mainly driven by a high-penetrant common allele. By contrast, it seems a multifactorial trait where genes such as LDLR could be involved.

Genetic markers of lipid metabolism genes associated with low susceptibility to HCV infection.

Due to the relation between lipids and Hepatitis C virus (HCV) life-cycle, we aimed to explore the existence of single nucleotide polymorphisms (SNPs) associated with low susceptibility to HCV-infection within lipid metabolism genes. This was a case-control study in three phases: (I) allelic frequencies of 9 SNPs within 6 genes were compared in 404 HCV-infected patients and 801 population controls; (II) results were validated in 602 HCV-infected individuals and 1352 controls; (III) results were confirmed in 30 HCV-exposed uninfected (EU) individuals. In phase I, only the LDLRAP1-rs4075184-A allele was differentially distributed in patients and controls (358 of 808 alleles [44.3%] and 807 of 1602 alleles [50.3%], respectively) (p = 0.004). In phase II, the A allele frequency was 547 of 1204 alleles (45.4%) in patients and 1326 of 2704 alleles (49.0%) in controls (p = 0.037). This frequency in EU was 36 of 60 alleles (60%), which was higher than that observed in patients from phase I (p = 0.018) and phase II (p = 0.027). The LDLRAP1-mRNA expression was lower in AA carriers than in non-AA carriers (median [Q1-Q3]: 0.85 [0.17-1.75] relative-units [ru] versus 1.71 [1.00-2.73] ru; p = 0.041). Our results suggest that LDLRAP1-rs4075184-A allele is associated with lower susceptibility to HCV-infection and with reduced expression of LDLRAP1-mRNA.