Cambios en las características epidemiológicas y en el pronóstico de la hepatitis crónica B en personas que viven con VIH / Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV

Introducción: La vacunación, los avances en el tratamiento frente al virus de la hepatitis B (VHB) y los cambios epidemiológicos producidos en España en las últimas décadas han podido modificar las características y el pronóstico de la hepatitis crónica B (HCB) en personas que viven con VIH (PVIH). Métodos: Estudio observacional retrospectivo donde se incluyeron PVIH-HCB en seguimiento en una unidad de referencia madrileña hasta el año 2019. Se comparó la incidencia y las características epidemiológicas y clínicas según el momento del diagnóstico (antes del año 2000 y posteriormente en periodos de cinco años). Además, se realizó un estudio longitudinal retrospectivo evaluando la tasa de mortalidad, descompensación hepática y factores asociados. Resultados: De 5.452 PVIH, 160 presentaban HCB en el momento basal (prevalencia 2,92%, IC 95%: 2,5-3,4), 85,6% hombres, edad mediana al diagnóstico 32,1 (27-37,2) años. La incidencia (2,4/100 pacientes-año) no varió en los diferentes periodos. Los pacientes diagnosticados antes del 2000 (n = 87) comparados con los diagnosticados entre 2015-2019 (n = 11) con mayor frecuencia eran nativos españoles (90,8 vs. 18,2%), habían consumido drogas intravenosas (55,2 vs. 0), tenían antecedentes de hepatitis C (40 vs. 9,1%) y delta (30,4 vs. 0) y mayor afectación hepática (24,1% cirróticos vs. 0). Tras un seguimiento de 20,4 años, 23 pacientes murieron (7,1/1.000 pacientes-año) y 19 presentaron descompensación hepática (4,9/1.000 pacientes-año), todos diagnosticados antes del año 2010. La mortalidad se asoció con mayor fibrosis hepática basal estimada por Fibroscan® (HR 1,06; IC 95%: 1,03-1,09). Conclusión: Las PVIH-HCB con diagnóstico previo al año 2000 son más frecuentemente de nacionalidad española, infectadas por vía parenteral y con mayor prevalencia de otras coinfecciones. Los pacientes diagnosticados antes del 2010 tienen peor pronóstico condicionado por presentar mayor grado de fibrosis hepática.(AU)

Introduction: Due to hepatitis B virus (HBV) treatment and vaccination during the last decades in Spain, epidemiological and prognosis of chronic hepatitis B (CHB) may have changed. Methods: Retrospective review of CHB–HIV coinfected patients in a single reference center in Madrid until year 2019. We compared incidence, epidemiological and clinical characteristics according diagnosis period (before 2000, 2000–2004, 2005–2009, 2010–2014, 2015–2019). A retrospective longitudinal study was done to assess mortality, related risk factors and hepatic decompensation. Results: Out of 5452 PLHIV, 160 had CHB (prevalence 2.92%; 95% CI: 2.5–3.4), 85.6% were men, median age 32.1 (27–37.2). Incidence rate did not change over the years (2.4/100 patients-year). PLHIV with CHB diagnosed before year 2000 (n = 87) compared with those diagnosed between 2015 and 2019 (n = 11) were more often native-Spanish (90.8% vs. 18.2%), had infected using intravenous drugs (55.2% vs. 0), were coinfected with hepatitis C (40% vs. 9.1%) or hepatitis delta virus (30.4% vs. 0) and had more severe liver disease (cirrhosis 24.1% vs. 0). After a median follow-up of 20.4 years, 23 patients died (7.1/1000 patients-year) and 19 had liver decompensation (4.9/1000 patients-year). All deaths and liver decompensation occurred in patients diagnosed before year 2010. Mortality was associated with higher liver fibrosis in Fibroscan® (HR 1.06, 95% CI: 1.03–1.09). Conclusion: The epidemiology of CHB in PLHIV in our cohort is changing with less native Spanish, more sexually transmitted cases and less coinfection with other hepatotropic virus. Patients diagnosed before 2010 have worst prognosis related to higher grades of liver fibrosis.(AU)

Sex differences in the effectiveness and tolerability of dolutegravir plus rilpivirine as a switch strategy in people living with HIV.

INTRODUCTION: Dolutegravir + rilpivirine (DTG + RPV) is an effective antiretroviral therapy regimen approved in clinical guidelines as a switch therapy for virologically suppressed people with HIV. Our study aimed to compare the effectiveness and tolerability of DTG + RPV in women and men in real-world clinical practice. METHODS: This was a retrospective analysis of treatment-experienced people with HIV from a large HIV unit who switched to DTG + RPV. We analysed treatment effectiveness, rates of adverse events and discontinuation, and metabolic changes after 48 weeks of treatment. HIV-RNA levels <50 copies/mL were analysed at 48 weeks using both intention-to treat analysis (where missing data were interpreted as failures) and per-protocol analysis (excluding those with missing data or changes due to reasons other than virological failure). Outcomes were compared between women and men based on sex at birth. RESULTS: A total of 307 patients were selected (71 women and 236 men). No transgender people were included. At baseline, women had lived with HIV infection and received antiretroviral therapy for longer than men (23.2 vs 17.4 years and 18.9 vs 14.2 years, respectively). In the intention-to-treat analysis, 74.6% (95% confidence interval [CI] 63.4-83.3%) of women and 83.5% (95% CI 78.2-87.7) of men had HIV-RNA <50 copies/mL. In the per-protocol analysis, 96.4% (95% CI 87.7-99) of women and 99% (95% CI 98.9-99.7) of men had HIV-RNA levels <50 copies/mL. Two women and two men had HIV-RNA >50 copies/mL at 48 weeks. Discontinuation due to adverse events was more frequent in women than in men: 12.7% vs 7.2% (p < 0.02). Neuropsychiatric and gastrointestinal events were the most frequently reported. A median (interquartile range) weight gain of 1.9 kg (0-4.2) in women and 1.2 kg (-1-3.1) in men was reported (median of differences between baseline visit and week 48); the remaining changes in metabolic parameters were neutral. CONCLUSIONS: DTG + RPV exhibited good and similar virological effectiveness in women and men in real-world settings. However, poorer tolerability and more treatment interruptions were observed in women.

Real-life data of immune recovery using bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people living with HIV. Results at 48-96†weeks of RETROBIC Study.

BACKGROUND: Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed. METHODS: We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF. We evaluated CD4+, CD8+ and CD4+/CD8+ ratio, efficacy and safety at weeks 48 and 96. RESULTS: The study comprised 1966 PLWH from 12 hospitals in Spain, of whom 80% were men, and the median age was 51.0 [42.0-57.0] years. The median time of HIV infection was 18.0 [10.0-27.0] years. No significant changes in CD4+, CD8+ T cells, or CD4+/CD8+ were observed after 96 weeks. Nevertheless, in women at weeks 48 and 96, we found a significant increase of CD4+ T cells and a significant decrease in CD8+ T cells. In patients ≥60 years at week 96, CD4 T cells significantly increased and CD8+ T cells significantly decreased at week 48. The on-treatment analysis revealed HIV-RNA <50 copies/mL in 95.6% (1700/1779) and 96.7% (1312/1356) of patients at weeks 48 and 96, respectively. The rates increased to 99.2% (1765/1779) and 99.7% (1352/1356) when considering HIV-RNA <200 copies/mL. No resistance mutations were detected in virologic failures. B/F/TAF discontinuations accounted for 10.2% (200). Simplification was the most common reason for discontinuation in 3.8% (74) of patients. CONCLUSION: In long-term virologically controlled PLWH, B/F/TAF achieved high efficacy rates and slightly improved immune status in women and individuals aged 60 and over after 48 and 96 of switching.

Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV.

INTRODUCTION: Due to hepatitis B virus (HBV) treatment and vaccination during the last decades in Spain, epidemiological and prognosis of chronic hepatitis B (CHB) may have changed. METHODS: Retrospective review of CHB-HIV coinfected patients in a single reference center in Madrid until year 2019. We compared incidence, epidemiological and clinical characteristics according diagnosis period (before 2000, 2000-2004, 2005-2009, 2010-2014, 2015-2019). A retrospective longitudinal study was done to assess mortality, related risk factors and hepatic decompensation. RESULTS: Out of 5452 PLHIV, 160 had CHB (prevalence 2.92%; 95%CI 2.5-3.4), 85.6% were men, median age 32.1 (27-37.2). Incidence rate did not change over the years (2.4/100 patients-year). PLHIV with CHB diagnosed before year 2000 (n = 87) compared with those diagnosed between 2015 and 2019 (n = 11) were more often native-Spanish (90.8% vs. 18.2%), had infected using intravenous drugs (55.2% vs. 0), were coinfected with hepatitis C (40% vs. 9.1%) or hepatitis delta virus (30.4% vs. 0) and had more severe liver disease (cirrhosis 24.1% vs. 0). After a median follow-up of 20.4 years, 23 patients died (7.1/1000 patients-year) and 19 had liver decompensation (4.9/1000 patients-year). All deaths and liver decompensation occurred in patients diagnosed before year 2010. Mortality was associated with higher liver fibrosis in Fibroscan® (HR 1.06, 95% CI 1.03-1.09). CONCLUSION: The epidemiology of CHB in PLHIV in our cohort is changing with less native Spanish, more sexually transmitted cases and less coinfection with other hepatotropic virus. Patients diagnosed before 2010 have worst prognosis related to higher grades of liver fibrosis.

Patterns of Sexualized Drug Use among Gay, Bisexual, and Other Men Who Have Sex with Men Living with HIV: Insights from a Comprehensive Study-The U-SEX-2 GESIDA 9416 Study.

BACKGROUND: Sexualized drug use (SDU) has become a public health concern in recent years. This study aimed to estimate the prevalence of SDU in gay, bisexual, and other men who have sex with men living with HIV (HIV + GBMSM) in Madrid during 2019/2020 and compare it with data from 2016/2017 in order to detect changes in patterns. METHODS: We analyzed the frequency of SDU in a sample of HIV + GBMSM attending HIV clinics, who participated in an anonymous online survey regarding sexual behavior and recreational drug use. The association between SDU, sexual risk behaviors, and STIs was evaluated. RESULTS: This study included 424 HIV + GBMSM, with a mean age of 40 (10.43) years. Overall, 94% (396) reported being sexually active. Additionally, 33% (140) had been diagnosed with an STI within the previous year. Moreover, 54% (229) had used drugs in the last year, 25% (107) engaged in SDU, and 16% (17) reported engagement in slamsex. After adjusting for confounding factors, SDU was associated with STIs, fisting, unprotected anal intercourse, and having >24 sexual partners in the last year. According to the DUDIT test scores, 80% (81) probably had problematic drug use (≥6 points), and 8% (8) probable drug dependence (≥25 points). When comparing the U-SEX-1 (2016/2017) data with the U-SEX-2 (2019/2020) data, no significant differences were found in the proportion of participants practicing SDU or slamming. CONCLUSIONS: The prevalence of SDU among HIV + GBMSM has remained high in recent years and without significant changes. The risk of problematic drug use among those who practice SDU is high. We observed a clear association between SDU, high-risk sexual behaviors, and STIs.

Mental Health in Children, Adolescents, and Youths Living with Perinatally Acquired HIV: At the Crossroads of Psychosocial Determinants of Health.

Here, we aim to describe mental health (MH) in a cohort of children, adolescents, and young adults living with perinatally acquired HIV (PHIV) in Spain and explore the treatment gap for mental disorders. We also aim to analyze the potential association between MH issues to psychosocial risk factors (PSRFs) and identify management priorities. We conducted a descriptive transversal study that included all cases of PHIV under follow-up in a reference hospital in Madrid. The study included patients undergoing follow-up in the pediatric outpatient clinic and youths transferred from pediatric to adult care units after 1997. Epidemiological, clinical, immunovirological, and treatment-related data were collected, including PSRF and adverse childhood experiences (ACEs). Of the 72 patients undergoing follow-up, 43 (59.7%) had already been transferred to the adult outpatient clinic. The patients' median age was 25 years (IQR 18-29), and 54.2% were women. Most patients were undergoing treatment (94.6%) and were virologically suppressed (84.7%). Although MH issues were present in 30 patients (41.7%), only 17 (56.7%) had been referred for evaluation to the Department of Mental Health, and only 9 (30%) had received a MH diagnosis. PSRFs were common (32% of participants had at least one PSRF) and were associated with MH issues and adherence issues (all p < 0.05). A multidisciplinary approach to address the psychological factors and social determinants of health is urgently needed, particularly during important life development stages, such as adolescence.

Prevalence and Temporal Trends of Autoimmune Diseases in People Living with HIV.

Since the introduction of modern antiretroviral treatment for HIV and hepatitis C virus (HCV), the pattern of autoimmune diseases (ADs) in people living with HIV (PWH) might have changed. This is a retrospective study in a cohort of 5,665 PWH at the HIV Clinic of Hospital Universitario La Paz (Spain) to estimate the prevalence of ADs from January 1990 to June 2020. We divided the timeline into four periods: <1996, 1996-2006, 2006-2015, and 2015-2020. In total 369 participants were diagnosed with at least one AD, with a prevalence of 5.3% (95% confidence interval 4.7-5.9). In total, 302 (81%) participants were diagnosed simultaneously or after HIV diagnosis. Most prevalent diseases were immune thrombopenia (IT) (n = 90), cutaneous psoriasis (n = 52), autoimmune thyroid disorders (n = 36), spondylarthritis (n = 24), and inflammatory bowel disease (IBD) (n = 21). There was a significant trend for more ADs in recent periods (p = .037). In recent years, participants with ADs were older, had a long time since HIV diagnosis, and had higher CD4+ T cell count and higher CD4+ T cell nadir (temporal linear trend p < .001). There was a change in the pattern of ADs over time with a decrease in IT and an increase in spondylarthritis, arthritis, IBD, and thyroid disorders. One hundred thirty-nine participants (46%) were coinfected with HCV, with a steady decline throughout the study period. Only cryoglobulinemia was statistically associated with HCV infection. AD increases over time in PWH with reasonable immune virological control. We observed a higher frequency of spondylarthritis, arthritis, autoimmune thyroid disorders, and IBD in recent years.

Change in metabolic parameters after switching from triple regimens with tenofovir alafenamide to dolutegravir-based dual therapy. Bi-lipid study.

INTRODUCTION: The use of tenofovir alafenamide (TAF) has been associated with increased cholesterol and body weight. Real-life data on the metabolic effects of switching from a TAF-based triple regimen to a dolutegravir (DTG)-based two-drug regimen (2-DR) are scarce. METHODS: A retrospective cohort study of patients who have switched from a triple TAF-based regimen to a 2-DR [DTG-lamivudine (DTG-3TC) or DTG- rilpivirine (DTG-RPV]) with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were percentage changes in lipid fraction, effectiveness and safety at 6 and 12 months [intention to treat (ITT), missing = failures]. RESULTS: A total of 118 patients (87 on DTG-3TC, 31 on DTG-RPV) were included. Median age was 51 years (interquartile range: 43-59), 86% were male, CD4 T-cell count was 692 cells/µL, and 98% viral load (VL) < 50 copies/mL. At 6 months there was a decrease in total and low-density lipoprotein cholesterol of 10.7 mg/dL [95% confidence interval (CI): 2.2-19.1; p ≤ 0.001] and 8.3 mg/dL (95% CI: 0.74-15.9; p = 0.026), respectively. There was a reduction in cardiovascular risk from 4.5% at baseline to 4% at 12 months (p = 0.040). Virological effectiveness as determined by ITT analysis was 85.6% at 6 months and 66.1% at 12 months. Seven patients (5.9%) withdrew from the 2-DR and there was no virological failure. CONCLUSIONS: In real life, switching from a triple regimen with TAF to DTG-3TC or DTG-RPV dual therapy improves the lipid profile and is an effective and well-tolerated strategy.

Changes in Quality of Sleep, Mood, and Other Neuropsychiatric Symptoms After Switching Dolutegravir/Lamivudine/Abacavir to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Randomized Study of People With Human Immunodeficiency Virus With Poor Sleep Quality: GESIDA 10418.

Background: Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods: This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results: We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions: In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

Eficacia en vida real del cambio a bictegravir/ emtricitabina/tenofovir alafenamida en pacientes previamente tratados con pautas triples que contienen rilpivirina / Real-world efficacy of switching to bictegravir/ emtricitabine/tenofovir alafenamide in pretreated patients with triple therapy containing rilpivirine

Objetivo. Analizar la eficacia y tolerabilidad de la estrategia de cambio desde regímenes basados en rilpivirina (RPV)a bictegravir/emtricitabina/tenofovir alafenamida (B/F/TAF) enla vida real.Métodos. Estudio unicéntrico, observacional y retrospectivo. Se seleccionaron pacientes que cambiaron de un régimencon RPV a B/F/TAF antes de febrero del 2020 analizándose losresultados después de 24 y 48 semanas. Se determinó el porcentaje que permanecía con carga viral indetectable, así comolos cambios en linfocitos CD4+, parámetros metabólicos y función renal.Resultados. Se incluyeron en el estudio 42 pacientes. 32de los 35 (91,4%) que completaron las 48 semanas de seguimiento tenían carga viral indetectable. El recuento de linfocitos CD4+ permaneció estable a las 24 y a las 48 semanas. Eltipo de análogos recibidos previamente no influyó en la respuestaConclusión. El cambio desde una triple terapia con RPV aB/F/TAF es una estrategia segura y eficaz en la vida real. (AU)

Objective. To analyze the efficacy and tolerability of thestrategy to change from rilpivirine (RPV) based regimens tobictegravir / emtricitabine / tenofovir alafenamide (B/F/TAF).Methods. Single-center, observational and retrospectivestudy. Patients who made the change to B/F/TAF before February 2020 were selected, analyzing the results after 24 and48 weeks. The percentage that remained with an undetectableviral load was determined, as well as the changes in CD4 +lymphocytes, metabolic parameters and renal function.Results. A total of 42 patients were included. Thirty-twoof the 35 patients (91.4%) who completed the 48 weeks offollow-up had an undetectable viral load. The CD4 + lymphocyte count remained stable at 24 and 48 weeks. The responseto B/F/TAF was not influenced by the two analogs previouslyreceived.Conclusion. Switching from triple therapy with RPV toB/F/TAF is a safe and effective strategy in real life. (AU)

Impact of preexisting nucleos(t)ide reverse transcriptase inhibitor resistance on the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide in treatment experience patients.

INTRODUCTION: Few clinical trials and cohort studies have evaluated the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) with preexisting M184V/I or other nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs). Real-world data are also scarce. METHODS: Retrospective review of treatment-experienced patients who started B/F/TAF in a cohort of PWH. HIV-RNA less than 50 copies/ml was analyzed at 48 weeks in an intention-to-treat (ITT) analysis (missing=failure) and per protocol analysis (patients with missing data or changes for reasons other than virological failure were excluded). Results were compared in patients with and without previous NRTI-RAMs. RESULTS: Five hundred and six PWH were included (16.2% women). Median age and time with HIV infection were 52.3 and 18.9 years, respectively. At baseline, viral load was less than 50 copies/ml in 440 patients (86.6%). Overall, 69 (13.6%) participants had documented preexisting NRTI-RAMs: 57 (11.2%) M184V/I and 30 (5.9%) tenofovir RAMs. In the ITT analysis, 83% (420/506) had HIV-RNA less than 50 copies/ml [82.2% (359/437) and 88.4% (61/69) in persons without and with NRTI-RAMs, respectively ( P  = 0.2)]. In the per protocol analysis 94.2% (420/445) had HIV-RNA less than 50 copies/ml [94.4% (359/380) vs. 93.8% (61/65); P  = 0.2]. A total of 61 participants were excluded from the per protocol analysis (23 missing data, 19 discontinued B/F/TAF because of toxicity, 13 for other reasons, and 6 died). CONCLUSION: Switching to B/F/TAF is well tolerated and effective in the real-world setting, even in patients with preexisting NRTI RAMs, such as M184V and RAMs conferring resistance to tenofovir. These results confirm the robustness of this combination.

Acute hepatitis B among HIV positive persons: A two-decade review of cases from a Spanish cohort.

PURPOSE: To review the incidence and characteristics of acute hepatitis B (AHB) in a large cohort of HIV infected persons from a low prevalence region during the last two decades. METHODS: Retrospective review of an HIV Cohort from a single reference centre in Madrid, Spain, between 2000 and 2018. AHB was diagnosed in persons with newly acquired HBAgS and acute hepatitis with positive IgM anti-HBc. RESULTS: Out of 5443 HIV+ patients in our cohort (3098 anti-HBc negative), 18 developed AHB from 2000 to 2018. The global incidence was 0.02 (0.01-0.04) per 100 patient-year in the entire population and 0.06 (0.01-0.1) per 100 patient-year in the anti-HBc negative population. A statistically significant decrease in AHB incidence was observed during these years (ß=-0.006; p=0.047). All 18 patients diagnosed with AHB were men, the majority (16) occurred in men who have sex with men. AHB was observed in 4 persons previously unresponsive to vaccination. Regarding antiretroviral treatment (ART), 15 were not receiving ART, two persons were on ART with any HBV active drugs and one person had lamivudine in the regimen. Two persons (11%) developed chronic hepatitis B. There were no cases of fulminant hepatitis. CONCLUSION: The incidence of AHB in HIV positive persons in our cohort was low and shows a progressive decline in the last 20 years. Cases occurred in persons not protected against VHB: not vaccinated or non-responders to vaccine that were not receiving tenofovir.

Acute hepatitis B among HIV positive persons: A two-decade review of cases from a Spanish cohort / Hepatitis B aguda en pacientes infectados por VIH en las dos últimas décadas en una cohorte española

ObjetivoRevisar la incidencia y las características de la hepatitis B aguda (HAB), en pacientes infectados por VIH en seguimiento durante las dos últimas décadas.MétodosRevisión retrospectiva de los casos de HAB en la cohorte de pacientes infectados por VIH y seguimiento en el Hospital Universitario La Paz, entre los años 2000 y 2018. La HAB se definió como la reciente aparición del AgS frente al virus de la hepatitis B (VHB) y anticuerpos anti-HBc+ de tipo IGM.ResultadosSe siguieron 5.443 pacientes VIH+, de ellos, 3.098 sin contacto previo con el VHB (anti-HBc negativo). Diagnosticamos 18 casos de HAB, lo que supone una incidencia de 0,02 (0,01-0,04) por 100 pacientes-año en toda la población y 0,06 (0,01-0,1) por 100 pacientes-año en aquellos anti-HBc negativo. Observamos una disminución significativa en la incidencia a lo largo de los años (β = -0,006; p = 0,047).Los 18 pacientes eran hombres y la mayoría (16) tenían sexo con hombres. En cuatro casos, la HAB se produjo en pacientes vacunados sin respuesta. Quince pacientes estaban sin tratamiento frente al VIH (TAR), dos recibían TAR sin drogas frente al VHB y uno tenía TAR con lamivudina, pero no tenofovir. No observamos ninguna hepatitis B grave, pero dos pacientes (11%) desarrollaron una hepatitis crónica B.ConclusiónLa incidencia de la HAB en pacientes VIH+ en nuestro hospital es baja y ha disminuido en los últimos 20 años. Aun así, seguimos viendo casos en pacientes sin protección para el VHB: sin vacunar o vacunados sin respuesta, que no reciben tenofovir.

PurposeTo review the incidence and characteristics of acute hepatitis B (AHB) in a large cohort of HIV infected persons from a low prevalence region during the last two decades.MethodsRetrospective review of an HIV Cohort from a single reference centre in Madrid, Spain, between 2000 and 2018. AHB was diagnosed in persons with newly acquired HBAgS and acute hepatitis with positive IgM anti-HBc.ResultsOut of 5443 HIV+ patients in our cohort (3098 anti-HBc negative), 18 developed AHB from 2000 to 2018. The global incidence was 0.02 (0.01–0.04) per 100 patient-year in the entire population and 0.06 (0.01–0.1) per 100 patient-year in the anti-HBc negative population. A statistically significant decrease in AHB incidence was observed during these years (β=−0.006; p=0.047).All 18 patients diagnosed with AHB were men, the majority (16) occurred in men who have sex with men. AHB was observed in 4 persons previously unresponsive to vaccination. Regarding antiretroviral treatment (ART), 15 were not receiving ART, two persons were on ART with any HBV active drugs and one person had lamivudine in the regimen. Two persons (11%) developed chronic hepatitis B. There were no cases of fulminant hepatitis.ConclusionThe incidence of AHB in HIV positive persons in our cohort was low and shows a progressive decline in the last 20 years. Cases occurred in persons not protected against VHB: not vaccinated or non-responders to vaccine that were not receiving tenofovir.

Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients.

BACKGROUND: A better understanding of the evolution of cirrhosis after hepatitis C virus (HCV) clearance is essential since the reversal of liver injury may not happen. We aimed to assess the evolution of plasma metabolites after direct-acting antivirals (DAAs) therapy and their association with liver disease scores in HIV/HCV-coinfected patients with advanced HCV-related cirrhosis. METHODS: We performed a prospective study in 49 cirrhotic patients who started DAAs therapy. Data and samples were collected at baseline and 36 weeks after SVR. Metabolomics analysis was carried out using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Inflammation-related biomarkers were analyzed using ProcartaPlex Immunoassays. RESULTS: At 36 weeks after SVR, patients experienced significant decrease in taurocholic acid, 2,3-butanediol, and LPC(18:0); while several phosphatidylcholines (LPC(16:1), LPC(18:1), LPC(20:4), and PC(16:0/9:0(CHO))/PC(16:0/9:0(COH)), 2-keto-n-caproic acid/2-keto-isocaproic acid and N-methyl alanine increased, compared to baseline. The plasma decrease in taurocholic acid was associated with a reduction in Child-Turcotte-Pugh (CTP) (AMR=3.39; q-value=0.006) and liver stiffness measurement (LSM) (AMR=1.06; q-value<0.001), the plasma increase in LPC(20:4) was related to a reduction in LSM (AMR=0.98; q-value=0.027), and the rise of plasma 2-keto-n-caproic acid/2-keto-isocaproic acid was associated with a reduction in CTP (AMR=0.35; q-value=0.004). Finally, plasma changes in taurocholic acid were directly associated with inflammation-related biomarkers, while changes in LPC(20:4) were inversely associated. CONCLUSIONS: Plasma metabolomic profile changed after HCV clearance with all oral-DAAs in HIV/HCV-coinfected with advanced HCV-related cirrhosis. Changes in plasma levels of LPC (20: 4), 2-keto-n-caproic acid/2-keto-isocaproic acid, and taurocholic acid were related to improvements in cirrhosis scores and inflammatory status of patients.

Chems4EU: chemsex use and its impacts across four European countries in HIV-positive men who have sex with men attending HIV services.

INTRODUCTION: Chemsex in a European context is the use of any of the following drugs to facilitate sex: crystal methamphetamine, mephedrone and gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) and, to a lesser extent, cocaine and ketamine. This study describes the prevalence of self-reported recreational drug use and chemsex in HIV-positive men who have sex with men (MSM) accessing HIV services in four countries. It also examines the problematic impacts and harms of chemsex and access to chemsex-related services. METHODS: This is a cross-sectional multi-centre questionnaire study of HIV-positive MSM accessing nine HIV services in the UK, Spain, Greece and Italy. RESULTS: In all, 1589 HIV-positive MSM attending HIV services in four countries completed the questionnaire. The median age of participants was 38 years (interquartile range: 32-46 years) and 1525 (96.0%) were taking antiretroviral therapy (ART). In the previous 12 months, 709 (44.6%) had used recreational drugs, 382 (24.0%) reported chemsex and 104 (6.5%) reported injection of chemsex-associated drugs ('slamsex'). Of the 382 engaging in chemsex, 155 (40.6%) reported unwanted side effects as a result of chemsex and 81 (21.2%) as a result of withdrawal from chemsex. The reported negative impacts from chemsex were on work (25.1%, 96), friends/family (24.3%, 93) and relationships (28.3%, 108). Fifty-seven (14.9%) accessed chemsex-related services in the past year, 38 of whom (67%) felt the service met their needs. DISCUSSION: A quarter of participants self-reported chemsex in the past 12 months. There were high rates of harms from chemsex across all countries, including negative impacts on work, friends/family and relationships. Although a minority of those engaging in chemsex accessed support, most found this useful.

COVID-19 in hospitalized HIV-positive and HIV-negative patients: A matched study.

OBJECTIVES: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. METHODS: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. RESULTS: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/µL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). CONCLUSIONS: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization.

HIV/HBV coinfection: temporal trends and patient characteristics, Spain, 2002 to 2018.

BackgroundRecent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking.AimLeveraged on a study designed to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002.MethodsThis cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients.ResultsThe prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL.ConclusionsThe prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.

Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort.

OBJECTIVES: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). METHODS: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. RESULTS: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9-10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41-3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26-0.94, p 0.031). CONCLUSIONS: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH.