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Background: Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. Methods: From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or 500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Interpretation: Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens.

Objective: The aim of this study was in seropositive subjects from Northern Mexico undergoing cART. Methods: This study included 186 PLWH under cART. The variables analyzed were CD4+ count, viral load, lipid profile, glucose, insulin resistance, anthropometric measures, family history of hypertension and cardiovascular disease, years of treatment and cART scheme. In this study, we used two well-established algorithmic models D:A:D (5-year period) and Framingham (10-year period) for assessing cardiovascular risk. Results: In our study, 51.3% of the PLWH had arterial hypertension; most of the subjects were diagnosed with overweight, hypertriglyceridemia and metabolic syndrome, which are factors that increase the risk of cardiovascular disease. After the assessment with the Framingham model, risk was considered as low, while for the D:A:D model was moderate for this population. Conclusions: PLWH receiving cART present factors that may increase the risk of early heart disease including hypercholesterolemia, hypertriglyceridemia, smoking and age. Although risk was low/moderate after the assessment, it is important to consider other factors such as age of the subjects, overweight/obesity, smoking or coinfections, in addition to years of exposure to cART, which could increase the rate of heart disease.

SummarySARS-CoV-2 infections lead to a high risk of hospitalization and mortality in diabetic patients. Why diabetic individuals are more prone to develop severe COVID-19 remains unclear. Here, we established a novel human kidney organoid model that mimics early hallmarks of diabetic nephropathy. High oscillatory glucose exposure resulted in metabolic changes, expansion of extracellular membrane components, gene expression changes determined by scRNAseq, and marked upregulation of angiotensin-converting enzyme 2 (ACE2). Upon SARS-CoV-2 infection, hyperglycemic conditions lead to markedly higher viral loads in kidney organoids compared to normoglycemia. Genetic deletion of ACE2, but not of the candidate receptor BSG/CD147, in kidney organoids demonstrated the essential role of ACE2 in SARS-CoV-2 infections and completely prevented SARS-CoV-2 infection in the diabetogenic microenvironment. These data introduce a novel organoid model for diabetic kidney disease and show that diabetic-induced ACE2 licenses the diabetic kidney to enhanced SARS-CoV-2 replication.

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.

REIPI-SEIMC COVID-19 group and COVID@HULP group., [Background] The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality., [Methods] In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model., [Findings] Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p, [Interpretation] Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated., [Funding] Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA., Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.

Estudios de cohortes; VIH; Pérdida de seguimiento Cohort studies; HIV; Lost to follow-up Estudis de cohorts; VIH; Pèrdua del seguiment Background Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90–90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods A scoping review was done following Arksey & O′Malley’s methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied. The project leading to these results (PISCIS Cohort) has received funding from “la Caixa” Banking Foundation under the project code LCF/PR/PR17/51120008. This work is supported by a grant from the Foundation Marató TV3 (project code 239/C/2018) aimed at the analysis of the LTFU patients of the PISCIS Cohort. The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

The main objective in the management of HIV-infected pregnant women is prevention of mother-to-child transmission; therefore, it is essential to provide universal antiretroviral treatment, regardless of CD4 count. All pregnant women must receive adequate information and undergo HIV serology testing at the first visit. If the serological status is unknown at the time of delivery, or in the immediate postpartum, HIV serology testing has to be performed as soon as possible. In this document, recommendations are made regarding the health of the mother and from the perspective of minimizing mother-to-child transmission.

Resumen Objetivo Proporcionar unas recomendaciones practicas para el manejo de la enfermedad metabolica osea en pacientes con virus de la inmunodeficiencia humana (VIH). Participantes Miembros de diferentes sociedades cientificas relacionadas con el metabolismo oseo y con la enfermedad VIH: Grupo de Estudio de Sida (GeSIDA), Sociedad Espanola de Endocrinologia y Nutricion (SEEN), Sociedad Espanola de Investigacion Osea y del Metabolismo Mineral (SEIOMM) y Sociedad Espanola de Fractura Osteoporotica (SEFRAOS). Metodos Se realizo una busqueda sistematica en PubMed de la evidencia disponible para cada aspecto, y se revisaron articulos escritos en ingles y en castellano con fecha de inclusion hasta 28 de mayo de 2013. Las recomendaciones se formularon segun el sistema GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Los autores trabajaron por grupos en la formulacion de cada apartado de las recomendaciones y posteriormente el documento global se discutio en una reunion conjunta. Todos los autores revisaron el documento escrito final y lo consensuaron. Conclusiones El documento establece unas recomendaciones practicas basadas en la evidencia acerca de la evaluacion y el tratamiento de la enfermedad metabolica osea en pacientes con VIH.

Resumen Introduccion Las guias GESIDA proponen pautas preferentes de inicio de tratamiento antirretroviral en pacientes infectados por el VIH. El objetivo de este analisis es comparar los costes y la eficacia de darunavir/r QD frente a otros inhibidores de la proteasa (IP) potenciados recomendados por GESIDA en pacientes naive. Metodos Mediante un modelo de coste-eficacia se compararon los IP/r recomendados como pautas preferentes o alternativas en pacientes naive, junto con un tratamiento de base con 2 ITIAN. La eficacia se midio mediante la respuesta virologica (carga viral Resultados El modelo estimo que el inicio del tratamiento en naive con darunavir/r QD se mostro como la opcion preferente basada en un IP/r mas coste-eficaz. El coste medio del TARGA por paciente respondedor era menor para darunavir/r (13.420 €) que para atazanavir/r (14.000 €) o lopinavir/r (13.815 €). Se estimo que darunavir/r seria el IP preferente mas eficiente, mientras que atazanavir/r QD y lopinavir/r BID resultarian opciones «dominadas», situandose fuera de la frontera de la eficiencia. Partiendo de un presupuesto fijo de 10 millones de €, se estimo que la pauta de inicio con darunavir/r QD conseguiria un mayor numero de pacientes respondedores (745) que con atazanavir/r QD (714) o lopinavir/r BID (724). Al mismo tiempo, darunavir/r QD reduciria el numero de pacientes que fracasarian al tratamiento (150) en comparacion con atazanavir/r QD (172) o lopinavir/r (286). Conclusiones Segun este modelo, darunavir/r QD es el IP/r preferente mas coste-efectivo para el tratamiento de la infeccion por el VIH-1 basado en IP/r en pacientes naive en Espana.

Objective: Currently, 12% of the Spanish population is foreign-born, and a third of newly diagnosed HIV-infected patients are immigrants. We determined whether being an immigrant was associated with a poorer response to antiretroviral treatment. Methods: Historical multicenter cohort study of naive patients starting HAART. The primary endpoint was time to treatment failure (TTF) defined as virological failure (VF), death, opportunistic disease, treatment discontinuation (D/C), or missing patient. Secondary endpoints were TTF expressed as observed data (TFO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/C not due to VF). A multivariate analysis was performed to control for confounders. Results: A total of 1090 treatment-naive HIV-infected patients (387 immigrants and 703 autochthonous) from 33 hospitals were included. Most immigrants were from Sub-Saharan Africa (28.3%) or South-Central America/Caribbean (31%). Immigrants were significantly younger (34 y vs 39 y), more frequently female (37.5% vs 24.6%), with less HCV coinfection than autochthonous patients (7% vs 31.3%). There were no differences in baseline viral load (4.95 Log(10) vs 4.98 Log(10)), CD4 lymphocyte count (193.5/mu L vs 201.5/mu L), late initiation of HAART (56.4% vs 56.0%), or antiretrovirals used. Cox-regression analysis (HR; 95%CI) did not show differences in TTF (0.89; 0.66-1.20), TFO (0.95; 0.66-1.36), or TVF (1.00; 0.57-1.78) between immigrants and autochthonous patients. Losses to follow-up were more frequent among immigrants (17.8% vs 12.1; p=0.009). Sub-Saharan African patients and immigrant females had a significantly shorter TTF. Conclusions: The response to HAART among immigrant patients was similar to that of autochthonous patients, although they had a higher rate of losses to follow-up. Sub-Saharan Africans and immigrant females may need particular measures to avoid barriers hindering antiviral efficacy. 1.923 JCR (2010) Q3, 23/33 Virology; Q4, 103/134 Immunology, 44/58 Infectious Diseases

Fundamento y objetivo Desconocemos si los pacientes con infeccion por el virus de la inmunodeficiencia humana (VIH) presentan mayor riesgo cardiovascular que los pacientes seronegativos. Nuestro objetivo ha sido analizar las diferencias en la presion arterial entre pacientes con infeccion por el VIH y controles sanos. Pacientes y metodo Analizamos retrospectivamente a todos los pacientes con infeccion por el VIH controlados en nuestro centro. El grupo control estuvo formado por voluntarios donantes de sangre, emparejados con aquellos por edad y sexo. Comparamos las cifras de presion arterial y el perfil lipidico entre ambos grupos. Evaluamos las siguientes variables: demograficas, fecha de diagnostico de la infeccion por el VIH, presencia de lipodistrofia, tratamiento antiretroviral y duracion, asi como factores de riesgo vascular. Resultados Evaluamos a 740 pacientes (el 75% varones) con una edad media de 41,8 anos. Encontramos una mayor prevalencia de hipertension en el grupo VIH comparado con el control (el 25 frente al 15%), asi como diferencias significativas entre las medias de presion arterial (p Conclusiones En este estudio observamos un aumento de la prevalencia de hipertension en los pacientes con infeccion por el VIH comparados con el grupo control. Ademas, en el grupo de pacientes con infeccion por el VIH, la prevalencia de lipodistrofia y de factores de riesgo vascular fue mayor entre los que presentaban hipertension comparados con los no hipertensos.

Entre los efectos adversos del tratamiento antirretroviral, probablemente el mas trascendente sea la toxicidad metabolica y sobre el tejido adiposo por sus eventuales consecuencias a largo plazo en terminos de riesgo cadiovascular. Dado que no todos los pacientes tratados con farmacos antirretrovirales la presentan, se ha postulado que debe existir una predisposicion genetica. La informacion actualmente disponible es, a menudo, no concordante. Se ha demostrado de forma consistente que los polimorfismos en los genes que codifican para las apolipoproteinas A5, C3 y E, para las proteinas transportadoras de esteres de colesterol (CETP), y en el cassette de enlace a ATP tipo A1 (ABCA1), modulan la generacion de la dislipidemia secundaria al tratamiento antirretroviral, especialmente si este contiene inhibidores de la proteasa (IP). En cuanto a los polimorfismos de la proteina de union al elemento regulador de esteroles tipo 1 (SREBP1), no existen evidencias concordantes. En el caso de la redistribucion de la grasa corporal o lipodistrofia, se ha estudiado si mutaciones en el ADN mitocondrial modulan el riesgo de aparicion, con resultados no concluyentes. Se ha descartado de forma rotunda la existencia de mutaciones en el gen de la lamina. Se han investigado los polimorfismos de genes que codifican para citocinas proinflamatorias, incluyendo el factor de necrosis tumoral alfa (TNF-α), la interleucina 1 beta (IL-1β) y la interleucina 6 (IL-6), con evidencias contradictorias en el caso del TNF-α, negativas en el caso de la IL-6 y datos que sugieren una asociacion positiva en el caso de la IL-1β. Por otra parte, los polimorfismos en el gen que codifica el factor derivado de celulas de la estroma-1 (SDF-1) y la proteina quimioatractiva de monocitos-1 (MCP-1) se han relacionado con la presencia de arteriosclerosis subclinica en pacientes infectados por el VIH-1 que reciben tratamiento antirretroviral.

Objetivo Estimar el impacto de la toxicidad asociada a los inhibidores de la transcriptasa inverse analogos de nucleosidos (ITIAN) en el coste total del tratamiento de pacientes con infeccion por el virus de la inmunodeficiencia humana tipo 1 (VIH-1). Metodos Se ha disenado un modelo farmacoeconomico a partir de datos obtenidos de un estudio prospectivo, multicentrico, observacional realizado en Espana (Estudio Recover). Los pacientes del estudio habian desarrollado un acontecimiento adverso (AA) asociado a un ITIAN que motivaba su suspension. En el analisis se incluyen todos los costes derivados de la toxicidad inducida por los ITIAN en los tratamientos antirretrovirales durante un ano. Los costes (valores del ano 2005) incluidos han sido: medicos directos (farmacos y manejo de AA) e indirectos (perdidas de productividad). La estimacion de los recursos relacionados con el manejo de los AA se ha realizado a traves de un panel de consenso de expertos clinicos. Resultados El incremento en el uso y coste de recursos sanitarios se correlaciona con la gravedad de todos los AA evaluados. El coste promedio total estimado por paciente ha sido de 4.012 €: 1.789 € por costes farmacologicos (ITIAN asociados con la discontinuacion de la terapia por AA) y 2.223 € por costes directos e indirectos del manejo de los AA (45 y 55%, respectivamente, de los costes totales). El 73% de los costes por paciente asociados a AA se deben a la lipoatrofia (560 €), lipodistrofia mixta (535 €) y neuropatia periferica (533 €). Conclusion En pacientes que desarrollan toxicidades asociadas a ITIAN, el coste economico de su manejo es superior al coste de adquisicion de los ITIAN y produce un incremento significativo en los costes totales del tratamiento de la infeccion por VIH-1. El coste del manejo de estas toxicidades deberia tenerse en cuenta en el diseno de estrategias de tratamiento antirretroviral mas eficientes.

Introducción En España algunos pacientes con VIH no reciben tratamiento antirretroviral (TAR), aun teniendo indicaciones para ello. Nuestro objetivo es identificar las barreras de inicio del TAR en pacientes con indicación para recibirlo. Métodos Encuesta transversal en 19 hospitales en España en 2012, incluyendo todos los pacientes que no recibían tratamiento y tenían al menos una indicación según las recomendaciones de Gesida/2011. Las posibles barreras se agruparon así (categorías no excluyentes): a) el médico considera que la indicación no es absoluta; b) el paciente no quiere iniciarlo; c) el médico considera que debe iniciarlo pero existe alguna limitación o contraindicación; y d) el paciente tiene viremia indetectable en ausencia de tratamiento. Resultados Se incluyeron 256 pacientes de los 784 programados; 84% hombres, mediana de edad 39 años; 57% homosexuales, 24% heterosexuales, 16% UDI. Mediana de tiempo desde el diagnóstico: 3 años, CD4: 501 células/mm3, carga viral 4,4 log. Indicaciones de TAR más frecuentes: CD4

El objetivo de este documento es actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el VIH del año 2010. La función renal debe monitorizarse en todos los pacientes e incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación CKD-EPI), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. También se revisan las indicaciones de la biopsia renal, cuándo enviar el paciente al nefrólogo y las indicaciones, evaluación y manejo del paciente en diálisis o del trasplante renal.

Background : The advent of combined antiretroviral therapy (ART) in the past decade has led to HIV suppression in most cases. Virological failure was the main reason for ART switch a few years ago; however, toxicity and treatment simplification have now gained importance due to the availability of more effective and convenient drugs. This study assessed the reasons for ART switch in daily practice. Materials and Methods : Observational retrospective study that included patients whose ART was switched between January 2011 and July 2012. Patients with any other switch during the follow-up period (until September 2013) were excluded. Results : A total of 246 patients were included. Main reasons for ART switch were simplification (33%) and toxicity (31%), followed by clinical trial inclusion (13%), virological failure (6%), drug interaction (4%), patient decision (3%), lack of adherence (2%), pregnancy (1%) and other (8%). Eighty patients switched to a simpler regimen (median age 48 [40–53], mean CD4 count 608±265 cells/cl, 89%

The main objective in the management of HIV-infected pregnant women is prevention of mother-to-child transmission; therefore, it is essential to provide universal antiretroviral treatment, regardless of CD4 count. All pregnant women must receive adequate information and undergo HIV serology testing at the first visit.We assembled a panel of experts appointed by the Secretariat of the National AIDS Plan (SPNS) and the other participating Scientific Societies, which included internal medicine physicians with expertise in the field of HIV infection, gynecologists, pediatricians and psychologists. Four panel members acted as coordinators. Scientific information was reviewed in publications and conference reports up to November 2012. In keeping with the criteria of the Infectious Diseases Society of America, 2levels of evidence were applied to support the proposed recommendations: the strength of the recommendation according to expert opinion (A, B, C), and the level of empirical evidence (I, II, III). This approach has already been used in previous documents from SPNS.The aim of this paper was to review current scientific knowledge, and, accordingly, develop a set of recommendations regarding antiretroviral therapy (ART), regarding the health of the mother, and from the perspective of minimizing mother-to-child transmission (MTCT), also taking into account the rest of the health care of pregnant women with HIV infection. We also discuss and evaluate other strategies to reduce the MTCT (elective Cesarean, child's treatment…), and different aspects of the topic (ARV regimens, their toxicity, monitoring during pregnancy and postpartum, etc.).

In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented.A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART.A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count500 cells/mm(3), 48%; having an uninfected sexual partner, 28%, and hepatitis C coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other limitations, 23%; and undetectable viral load, 6%.The majority of subjects with ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing.

To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients.Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS).A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content.The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients.

GESIDA (AIDS Study Group) has proposed preferred regimens of antiretroviral treatment as initial therapy in HIV infected patients. The objective of this analysis is to compare the costs and effectiveness of darunavir/r QD and other ritonavir-boosted (/r) protease inhibitors (PIs) currently recommended in GESIDA guidelines for treatment-naïve patients.A cost-efficacy model compared the boosted PIs recommended as preferred or alternative treatment choices, each used with a nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by 48-week virological response (viral load 50 copies/mL) adjusted by baseline viral load and CD4 cell count. To generate efficiency frontiers and cost-efficacy ratios, one-year antiretroviral therapy costs in Spain, and 48-week efficacy values were used.The model estimated that starting treatment with darunavir/r QD was the most cost-effective choice compared with the other preferred PI/r based therapies. The average cost per patient with a virological response was lower for darunavir/r QD (13,420€) than for atazanavir/r QD (14,000€), or lopinavir/r BID (13,815€). Among the preferred PI/r-based therapies, darunavir/r QD also was estimated to be the most efficient option for treatment-naïve patients. Atazanavir/r QD and lopinavir/r BID were found to be «dominated» by darunavir/r) and, consequently, were outside the efficiency frontier of PI/r-based first-line treatment. Given a fixed budget of 10 million euros for PI/r-based first-line therapy, the model estimated that darunavir/r QD would yield more responders (745) than atazanavir/r QD (714), or lopinavir/r BID (724). At the same time, darunavir/r QD would reduce the number of individuals failing treatment (150) compared with atazanavir/r QD (172) and lopinavir/r BID (286).In this model, darunavir/r QD was found to be the most cost-effective choice, among the preferred PI/r-based therapies recommended in the Spanish guidelines for treatment-naïve patients.

It is not known whether human immunodeficiency virus (HIV)-infected patients present, compared to non-HIV controls, higher vascular risk factors. Our objective was to analyze whether there are differences in blood pressure in HIV patients compared to non-HIV controls.We retrospectively analyzed all HIV patients controlled in our centre, who were compared with a control group of blood donors, matched for age and sex, blood pressure and lipid profile. We evaluated the following variables: demographic data, date of HIV diagnosis, presence of lipodystrophy, antiretroviral treatment, duration of this treatment, and vascular risk factors.We evaluated 740 patients (mean age: 41.8 years; 75% men). We detected a higher prevalence of hypertension in the HIV group (25% vs. 15%) with a significant difference in the mean systolic/diastolic blood pressure between both groups (p0.0001). In the HIV group, hypertensives were older than normotensives, and had higher prevalence of lipodystrophy and higher total cholesterol with a shorter disease duration (75 vs 85 months). In the total group of hypertensives, HIV patients were younger than non-HIV (44.2 vs 47.9 years; p0.009) and had higher total cholesterol values (5.44 vs 5.18 mmol/l; p0.052).We found a higher prevalence of hypertension in HIV patients compared with matched controls, as well as a higher prevalence of lipodystrophy and vascular risk factors in hypertensive HIV patients compared with non-hypertensive.

Among the adverse effects attributed to antiretroviral therapy, one of the most striking is probably the appearance of the lipodystrophy syndrome and its associated metabolic derangements, given its potential long-term effect as a cardiovascular risk factor. Since not all patients who receive antiretroviral drugs experience these adverse effects, a host genetic predisposition has been postulated. However, currently available data on this issue is inconclusive and preliminary. It has been consistently demonstrated that polymorphisms in the genes that encode for apolipoproteins A5, C3 and E, for the cholesterol ester transporter proteins (CETP), and in the ATP binding cassette type A1 (ABCA1) influence the development of dyslipidemia in patients treated with antiretroviral drugs, particularly if the therapeutic regimen includes protease inhibitors. Data on the effect of polymorphisms in the sterol regulatory ester binding protein type 1 (SREBP1) are inconsistent. The effect of mitochondrial DNA mutations on the risk of lipodystrophy has been assessed, with inconclusive data. No polymorphisms in the lamin A gene have been detected. Investigations have assessed the effect of diverse polymorphisms in the genes that encode for several proinflammatory cytokines such as tumour necrosis factor alpha (TNF-alpha), interleukin-1-beta (IL-1beta) and interleukin-6 (IL-6). The results show inconsistent data in the case of TNF-alpha, no association in the case of IL-6, and preliminary positive associations in IL-1beta. In contrast, polymorphisms in the genes encoding for stromal derived factor 1 (SDF-1) and for monocyte chemoattractant protein 1 (MCP-1) have been shown to influence the development of subclinical atherosclerosis in HIV-1-infected patients treated with antiretroviral drugs.

To study the prevalence of delayed diagnosis of HIV infection and associated factors.A cross sectional study of patients included in the Spanish VACH cohort who had been diagnosed with HIV infection between 1997 and 2002 was performed. Delayed diagnosis was defined as patients diagnosed with HIV infection and AIDS simultaneously or within the first month after the first positive serologic test, or those with a first CD4+ cell count below 200/ml. The epidemiological characteristics of these patients were compared with those of the remaining patientsOf 2,820 new cases of HIV infection, delayed diagnosis was found in 506 (18%). These patients differed from the remaining patients in their lower mean age and higher HIV viral load, as well as in their distribution by sex (higher proportion of males), occupational status, history of incarceration in prison, and HIV-risk transmission group. The median survival during follow-up was significantly lower among AIDS patients with a delayed diagnosis.Delayed diagnosis remains a cause for concern in our environment, due to its magnitude and its association with mortality. Some epidemiological characteristics provide clues to guide future programs directed at increasing information and improving prevention.

To estimate the impact of toxicity related to nucleoside analogue reverse transcriptase inhibitors (NRTI) on the total cost of medical care in HIV-1-infected patients.. A pharmacoeconomic model was developed from the data obtained by a prospective, observational, multicenter study performed in Spain (Recover). The study patients had developed one NRTI-associated adverse event (AE) that justified discontinuation of treatment with the drug. All costs derived from NRTI-associated AEs in the HAART regimens of HIV-1-infected patients over a period of one year were assessed. The cost assessment (2005 values) included direct medical costs (drugs and AE management) and indirect costs (loss of productivity). The healthcare resources used in AE management were estimated by an expert panel of clinicians.The use and cost of resources rose with increasing severity of all the AE. The average total cost per patient was estimated to be 4012 euro, which included 1789 euro in drug costs (NRTI associated with therapy discontinuation due to AE), and 2223 euro in direct and indirect costs of AE management (45% and 55% of total cost, respectively). Seventy-three per cent of AE-associated costs per patient came from lipoatrophy (560 euro), lipodystropy (535 euro) and peripheral neuropathy (533 euro).Management of NRTI-related toxicities is more costly than NRTI acquisition and produces a significant increase in the overall healthcare expenditure for HIV-1-infected patients. This fact should be taken into account when designing the most efficient antiretroviral treatment strategies.

Objective: To study the prevalence of delayed diagnosis of HIV infection and associated factors. Methods: A cross sectional study of patients included in the Spanish VACH cohort who had been diagnosed with HIV in- fection between 1997 and 2002 was performed. Delayed diag- nosis was defined as patients diagnosed with HIV infection and AIDS simultaneously or within the first month after the first positive serologic test, or those with a first CD4 + cell count below 200/ml. The epidemiological characteristics of these patients were compared with those of the remaining patients Results: Of 2,820 new cases of HIV infection, delayed diag- nosis was found in 506 (18%). These patients differed from the remaining patients in their lower mean age and higher HIV viral load, as well as in their distribution by sex (higher pro- portion of males), occupational status, history of incarceration in prison, and HIV-risk transmission group. The median sur- vival during follow-up was significantly lower among AIDS pa- tients with a delayed diagnosis. Conclusions: Delayed diagnosis remains a cause for con- cern in our environment, due to its magnitude and its asso- ciation with mortality. Some epidemiological characteristics pro- vide clues to guide future programs directed at increasing information and improving prevention.

Objetivo: Actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Métodos: Este documento ha sido consensuado por un panel de expertos del Grupo de Estudio de Sida (GESIDA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), de la Sociedad Española de Nefrología (S.E.N.) y de la Sociedad Española de Química Clínica y Patología Molecular (SEQC). Para la valoración de la calidad de la evidencia y la graduación de las recomendaciones se ha utilizado el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Resultados: La evaluación renal debe incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación chronic kidney disease epidemiological collaboration [CKD-EPI]), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. En este documento se revisan las indicaciones de derivación del paciente a Nefrología y las de la biopsia renal, así como las indicaciones y la evaluación y el manejo del paciente en diálisis o del trasplante renal. Conclusiones: La función renal debe monitorizarse en todos los pacientes con infección por el VIH y este documento pretende optimizar la evaluación y el manejo de la afectación renal.

More than 15 years after the introduction of highly active antiretroviral therapy, HIV/HAART-associated lipodystrophy syndrome still shadows the indisputable efficacy of antiretroviral therapy. Several issues related to this complication (prevalence, diagnosis, pathogenesis, prevention, or clinical management) have not been completely clarified. However, in the last years, substantial progress has been made in elucidating some of these basic aspects. This includes a better knowledge of the pathogenic mechanisms underlying HIV/HAART-associated lipodystrophy syndrome such as genetic host determinants, the impact of HIV infection per se, as well as the contribution of antiretroviral therapy. In regard to treatment, we have learned that certain drugs are especially prone to cause HIV/HAART-associated lipodystrophy syndrome (i.e. thymidine analogues). Pharmacological interventions to treat this condition have yielded mostly disappointing results, and the only intervention which offers an immediate aesthetical improvement for patients with HIV/HAART-associated lipodystrophy syndrome is plastic surgery. Even under the most favorable conditions (ideal host genetic make-up, and the timely initiation of HIV therapy with less toxic drugs), current data show that HIV/HAART-associated lipodystrophy syndrome is a complication of HIV infection and/or antiretroviral treatment that we are unable to avoid. In the context of HIV-1-infected patients under long-term antiretroviral therapy, fat toxicity is still the dark side of the rainbow.