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Background: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimens, few data are available on mortality in people with HIV treated with INSTIs in routine care. Therefore, we compared all-cause mortality between different INSTI-based and non-INSTI-based regimens in adults with HIV starting ART from 2013 to 2018. Methods: This cohort study used data on people with HIV in Europe and North America from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and UK Collaborative HIV Cohort (UK CHIC). We studied the most common third antiretroviral drugs (additional to nucleoside reverse transcriptase inhibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efavirenz, and others. Adjusted hazard ratios (aHRs; adjusted for clinical and demographic characteristics, comorbid conditions, and other drugs in the regimen) for mortality were estimated using Cox models stratified by ART start year and cohort, with multiple imputation of missing data. Findings: 62 500 ART-naive people with HIV starting ART (12 422 [19·9%] women; median age 38 [IQR 30-48]) were included in the study. 1243 (2·0%) died during 188 952 person-years of follow-up (median 3·0 years [IQR 1·6-4·4]). There was little evidence that mortality rates differed between regimens with dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug. However, mortality was higher for raltegravir compared with dolutegravir (aHR 1·49, 95% CI 1·15-1·94), elvitegravir (1·86, 1·43-2·42), rilpivirine (1·99, 1·49-2·66), darunavir (1·62, 1·33-1·98), and efavirenz (2·12, 1·60-2·81) regimens. Results were similar for analyses making different assumptions about missing data and consistent across the time periods 2013-15 and 2016-18. Rates of virological suppression were higher for dolutegravir than other third drugs. Interpretation: This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality. We would like to thank our funders (US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council) and all patients and the clinical teams associated with the participating cohort studies. The antiretroviral therapy cohort collaboration is funded by the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026209). UK Collaborative HIV Cohort is funded by the UK Medical Research Council (grant numbers G0000199, G0600337, G0900274, and M004236/1). JACS is funded by National Institute for Health Research Senior Investigator award (NF-SI-0611-10168). AT is funded by the Wellcome Trust under a Sir Henry Wellcome Postdoctoral Fellowship (222770/Z/21/Z). Funding for the individual antiretroviral therapy cohort collaboration cohorts included in this analysis was from Alberta Health, Gilead, National Agency for AIDS Research (France REcherche Nord&Sud Sida-hiv Hépatites), the French Ministry of Health, the Austrian Agency for Health and Food Safety, Stichting HIV Monitoring, the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment, the TP-HIV by the German Centre for Infection Research (NCT02149004), Instituto de Salud Carlos III (through the Red Temática de Investigación Cooperativa en Sida [RD06/006, RD12/0017/0018, and RD16/0002/0006]) as part of the Plan Nacional I + D + i. Other funders of the individual cohorts participating data for this analysis are ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional, ViiV Healthcare, Preben og Anna Simonsens Fond, ANRS-Maladies infectieuses émergentes, Institut National de la Santé et de la Recherche Médicale (INSERM), Bristol Myers Squibb, Janssen, Merck, the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026230), the Spanish Ministry of Health, the Swiss National Science Foundation (grant 33CS30_134277), Centers for AIDS Research Network of Integrated Clinical Systems (1R24 AI067039-1, P30-AI-027757), the US Department of Veterans Affairs, the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026224, U01-AA026209, U24-AA020794), the Veterans Health Administration Office of Research and Development, and the US National Institute of Allergy and Infectious Diseases (Tennessee Center for AIDS Research P30 AI110527). Sí

Background Fungal infections are an uncommon entity, especially those produced by species other than Aspergillus. Despite this, they are usually more virulent and difficult to treat. In the following case report, we present the case of an immunocompromised patient suffering from two serious opportunistic infections in the same episode: the first of these, Nocardia multilobar pneumonia; and the second, skin infection by Scedosporium apiospermum. These required prolonged antibacterial and antifungal treatment.Case presentation This case is a 71 year-old oncological patient admitted for recurrent pneumonias that was diagnosed for Nocardia pulmonary infection. Nervous system involvement was discarded and cotrimoxazol was started. Haemorrhagic skin ulcers in the lower limbs appeared after two weeks of hospital admission. We collected samples which were positive for Scedosporium apiospermum and we added voriconazole to the treatment. As a local complication, the patient presented a deep bruise that needed debridement. We completed 4 weeks of intravenous treatment with slow improvement and continued with oral treatment until the disappearance of the lesions occurs.Conclusions Emerging fungal infections such as Scedosporium apiospermum are increasing globally. These species are more difficult to diagnose and treat, due to factors of the fungus itself and the characteristics of the patient, and therefore clinicians must be aware of their complications.

This article aims to review the main information taken into account for the update of the GESIDA PLWH quality indicators. Finally 54 indicators covering a major part of the clinical activity in PLWH were defined. They evaluate the detection and diagnosis of PLWH, their follow-up and prevention, initiation and adaptation of ART, women's specific aspects, comorbidities, hospitalization, and AIDS-related mortality.

The present study sought to describe the use of generic drugs and single-tablet regimen (STR) de-simplification for the treatment of human immunodeficiency virus (HIV) infection among 41 hospitals from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). In June 2018, we collected information on when generic antiretroviral drugs (ARVs) were introduced in the different hospitals, how the decisions to use them were made, and how the information was provided to the patients. Most of the nine available generic ARVs in Spain by June 2018 had been introduced in at least 85% of the participating hospitals, except for zidovudine (AZT)/lamivudine (3TC) and AZT. The time difference between the effective marketing date of each generic ARV and its first dispensing date in the hospitals was much shorter for the more recently approved generic ARV since the year 2017. However, only up to 20% of the hospitals de-simplified efavirenz (EFV)/tenofovir disoproxil (TDF)/emtricitabine (FTC), dolutegravir (DTG)/abacavir (ABC)/3TC, and rilpivirine (RPV)/TDF/FTC (to generic EFV+TDF/FTC, DTG+generic ABC/3TC, and RPV+generic TDF/FTC, respectively), whereas the generic STR EFV/TDF/FTC was introduced in 87.8% of the centers. The median times between the date of effective marketing of generic TDF/FTC and the date of de-simplification of EFV/TDF/FTC and RPV/TDF/FTC were 723 [interquartile range (IQR): 369-1,119] and 234 (IQR: 142-264) days, respectively; this time was 155 (IQR: 28-287) days for de-simplification of DTG/ABC/3TC. In conclusion, despite the widespread use of generic ARVs, STRs de-simplification was only undertaken in20% of the hospitals. There was wide variability in the timing of the introduction of each generic ARV after they were available in the market.

Background Information on the characteristics of patients with nosocomial influenza and associated complications is scarce. This study compared epidemiological and clinical characteristics of patients admitted with hospital‐acquired influenza (HAI) to those with community‐acquired influenza (CAI) and analyzed risk factors associated with complications. Methods This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during the influenza season in Spain (October to May) from 2012‐2013 to 2015‐2016. Symptom onset before admission was included as CAI, and 2 days after admission or within 48 hours after previous discharge were considered as HAI. Results Overall, 666 patients with laboratory‐confirmed influenza were included; 590 (88.6%) and 76 (11.4%) had CAI and HAI, respectively. Baseline characteristics and vaccination rates were similar in both groups. Patients with HAI had significantly fewer symptoms, less radiological alterations, and earlier microbiological diagnosis than those with CAI. Eighty‐five (14.4%) and 20 (27.6%) CAI and HAI patients, respectively, experienced at least one complication, including septic shock, admission to the intensive care unit, mechanical ventilation or evolution to death (any one, P = .003). Univariate and multivariate binary logistic regression was performed to assess independent risk factors associated with the occurrence of complications: nosocomial infection, diabetes, oseltamivir treatment, having received no vaccination, microbiological delay, dyspnea, and the state of confusion were the most important significant factors. Conclusions Our study shows the need to implement microbiological diagnostic measures in the first 48 hours to reduce HAI frequency and associated complications.

The incidence of anal cancer has increased in recent years, making screening and early detection of anal intraepithelial neoplasia (AIN) a necessity in patients at risk.A descriptive observational study of homosexual patients (MSM) or women with CIN III, with human immunodeficiency virus (HIV) infection included in an AIN detection screening program was carried out between March 2016 and September 2019.We have performed 695 anal smears, 156 with results of LSIL (low-grade lesion) or HSIL (high-grade lesion) (22.4%), 116 high resolution anoscopy (HRA) 75.3% of patients with altered cytology. We have 403 biopsies being 84% pathological, 197 biopsies of AIN 1 (49%), 96 AIN II and III (24%), 44 were condylomas (11%) and the rest, 16%, normal mucosa.The high prevalence of premalignant lesions and the improvement in the staging of lesions after treatment recommend this protocol.

Resumen Este estudio se ha centrado en las actuaciones a nivel politico y administrativo que se han realizado en Espana en relacion con la implementacion de la profilaxis preexposicion (PrEP) al VIH. Se ha analizado todo tipo de iniciativas formales por parte de los actores politicos y administrativos implicados. Las fuentes utilizadas son las fuentes oficiales publicas. Hasta febrero de 2018, la PrEP no ha sido implementada. La decision depende de los niveles estatal y autonomico. El Ministerio de Sanidad y algunas Comunidades Autonomas trabajan en diversas intervenciones sin establecer un calendario de implementacion. Los partidos politicos por su parte han promovido escasas iniciativas relacionadas con la implementacion de la PrEP. En el terreno juridico, se han producido vaivenes legales relacionados con la extension de la patente. El papel de los organos intergubernamentales e interdepartamentales es vital para la implementacion de la PrEP.

Since its first identification in the early 1990s, Mycobacterium genavense has been considered and opportunistic pathogen. It mainly causes gastrointestinal symptoms, but also disseminated infections in severely immunosuppressed patients. Sclerosing mesenteritis is a long-term complication with high morbidity and mortality. As it is a rare condition, there are no specific guidelines for its management. We report a challenging case of persistent M. genavense infection, and propose surgery as an alternative treatment strategy.A 38-year-old Caucasian man presented to the emergency room with fever, abdominal pain, and night sweats for 3 months. HIV screening revealed a previously unknown HIV-1 infection, with a CD4 cell count of 216 cell/µL and viral load of 361.000 copies/mL at diagnosis. A body CT-scan showed mild splenomegaly as well as mesenteric and retroperitoneal enlarged lymph nodes. Fine needle aspiration revealed the presence of acid-fast bacilli, but mycobacterial cultures were negative. In the second sample, 16S RNA sequencing yielded a diagnosis of M. genavense infection. Despite 2 years of corticosteroids and antimycobacterial treatment excluding rifampicin due to a severe cutaneous reaction, there was no clinical improvement and an increase in the mesenteric lymph node size was observed, with a sclerosing transformation of the mesentery. A surgical approach was proposed to release small bowel loops and to remove fibrin. A second surgery was required due to an acute peritonitis ought to yeyunal segmental isquemia and perforation. Finally, the patient evolved favorably, and antimycobacterial drugs were suspended without relapse.Despite a prolonged multidrug strategy, some patients develop persistent M. genavense infection. Once sclerosing mesenteritis is established, clinicians have few treatment options. Surgery should be considered in patients with sclerosing mesenteritis or bowel obstruction. The combination of medical and surgical treatment could be a potential cure for these patients.

Summary Background Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. Methods We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. Findings We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0–52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31–1·83), men who have sex with men (1·42, 1·09–1·86), and those with four or more chronic comorbidities (1·46, 1·09–1·97). Age at least 75 years (5·2, 1·8–15·3), non-Spanish origin (2·1, 1·3–3·4), and neuropsychiatric (1·69, 1·07–2·69), autoimmune disease (1·92, 1·14–3·23), respiratory disease (1·84, 1·09–3·09), and metabolic disease (2·59, 1·59–4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). Interpretation People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. Funding Fundacio "la Caixa". Translations For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.

Background: There are few shared assistance programs with Primary Health Care (PHC) in PLWH. The aim was to develop a Pilot Program of shared HIV care in PLWH ensuring proper HIV control. Methods: Design: Prospective pilot project of a shared care intervention.Setting: HIV specialized outpatient consultations for HIV infection at Son Espases University Hospital which serves 2000 patients. Subjects: Patients who attended HIV specialized consultation between January 1st and June 30th, 2017. Intervention: Basal questionnaire on health services used by patients. HIV Training Program on HIV in Primary Health Care (PHC). Pilot Program of shared assistance (PPAC) with PHC. Main Outcomes: Maintenance of undetectable HIV viral load, antiretroviral therapy (ART) adherence, AIDS and non-AIDS events, loss of follow up, and satisfaction questionnaire. Results: The basal questionnaire was filled out by 918 patients, with 108 (11.7%) patients reporting neither knowing nor having been visited by their GP. A total of 93 patients were included in the PPAC, with a mean age of 49.9 years (SD 11.7), and an average of 14.6 years since the HIV diagnosis. Eleven patients were followed up for less than six months and were excluded from the analysis. Median follow-up during the PPAC of the remaining 82 patients was 728 days (IQR 370-1070). Sixteen patients dropped out of the PPAC (19.5%), three died, three were lost to follow up, one was withdrawn due to medical criteria, and nine withdrew voluntarily.No patient presented any AIDS defining events, although eight patients presented non-AIDS events. All the patients had undetectable viral load (VL) and average ART adherence was 99.4% (SD1.4). The patient’s satisfaction score with PPAC was 8.64 (SD2.5).Conclusion: It is possible to establish shared care programs with PHC in selected patients with HIV infection, thereby reducing hospital visits while maintaining good adherence and virological control and achieving high patient satisfaction.

Introduction: Since 2015, integrase strand transfer inhibitors (INSTI)-based regimens have been considered as the preferred option for antiretroviral therapy (ART)-naive patients. The main objective of this study was to identify the ART-regimens selected for treatment-naive patients during 2015 in two tertiary hospitals, determine the rate of virological failure at 24 and 48 weeks, and compare the results with those of previous years (2012-2014). Material and methods: Four-year retrospective study. Adult ART-naive patients who had started treatment between 2012 and 2015 were selected. Clinical data, laboratory tests performed, and ART selected were recorded. Results: A total of 536 patients were included, 137 from 2015 and 399 from 2012-2014. The most common ART regimens prescribed in 2015, compared to 2012-2014, were INSTI-based regimens (68.6% vs. 4.8%), followed by non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (20.4% vs. 52.8%) and PI-based regimens (10.9% vs. 42.5%). Most patients received a single-tablet regimen (78.8% vs. 51.9%). In 2015, 72.3% of patients had a viral load (VL) < 50 copies/ml at week 24 and 83.9% at week 48, compared to 55.1% and 74.7%, respectively, in 2012-2014. During the 48-week follow-up, the ART regimen was changed in 22.6% of patients in 2015 and 29.3% in 2012-2014. The main reason was simplification (45.2% vs. 22.2%) followed by side effects (25.8% vs. 38.5%). Conclusions: In 2015, INSTI-based regimens were prescribed in nearly 70% of ART-naive patients. This change in trend in the starting ART regimen results in a greater number of patients achieving a VL < 50 copies/ml at weeks 24 and 48 and in a reduction in ART changes due to adverse effects.

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

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.

Objectives: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). Methods: Retrospective, multicenter, cohort study of PJI by S. aureus (2003–2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. Results: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. Conclusions: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

Introduction International travelers have grown significantly over last years, as well as imported diseases from tropical areas. Information in pediatric population is scarce. We describe demographic and clinical characteristics of febrile children coming from the tropics. Methods Retrospective review of patients under 18 years old, presenting at a tertiary hospital and surrounding primary health care centers between July 2002 and July 2018 with a stay in a tropical region during the previous year. Patients were selected from microbiological charts of thick smears for malaria or dengue serologies. Results 188 patients were studied: 52.7% were born in Spain with a median age of 3.0 years old (IQR 1.5–8.0). Main regions of stay were Sub-Saharan Africa (54.8%) and Latin America (29.8%), mostly for visiting their friends and relatives (56.3%), followed by recent arrival migrants (32.4%). Only 34% of travelers attended pre-travel consultation. More than 80% of these febrile children attended directly the Emergency Room. The most frequent diagnoses were febrile syndrome without source (56.4%), respiratory condition (15.4%) and acute diarrhea (11.7%). Around a half (52.1%) were managed as outpatients, but 46.2% were hospitalized and 7.4% were admitted to Intensive Care Unit. No specific diagnosis was achieved in 24% of cases. However, 29.7% were diagnosed with malaria. Conclusion Children with fever coming from tropical areas were at risk of severe infectious diseases. Malaria was diagnosed in one out of four and 7% required admission in PICU. This information emphasizes the need of reinforcing training about tropical diseases among first line physicians.

Background.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success.Methods.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy.Results.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using β-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with β-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34).Conclusions.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of β-lactams are confirmed and maybe also a potential benefit from adding rifampin.

Resumen Introduccion En 2010 el Grupo Espanol de Estudio de SIDA (GeSIDA) desarrollo 66 indicadores de calidad asistencial. Nuestro objetivo es determinar cuales de estos indicadores se asocian a mortalidad y/o ingreso, y realizar una evaluacion preliminar de la utilidad de un indice predictor de mortalidad e ingreso. Metodos Estudio de cohortes retrospectivo realizado en el Hospital Universitario Son Espases. Los pacientes con infeccion por el virus de la inmunodeficiencia humana incluidos fueron aquellos que iniciaron seguimiento en consultas entre el 1 de enero de2000 y el 31 de diciembre de 2012. Se realizo analisis descriptivo de las variables demograficas y de los indicadores, y un estudio de regresion logistica para valorar la asociacion entre los indicadores y riesgo de mortalidad/ingreso. Se calcularon indices predictores de mortalidad e ingreso para pacientes en seguimiento y en tratamiento. Resultados Fueron incluidos 1.944 pacientes (media de edad: 37 anos, el 78,8% varones). En el analisis multivariante relativo a mortalidad, los indicadores asociados en pacientes en seguimiento fueron el 7, 16 y 20 y en pacientes en tratamiento se anaden el 35 y 38. En el analisis multivariante relativo a ingreso, los indicadores asociados en pacientes en seguimiento fueron los mismos que para mortalidad, ademas del 31, y en el grupo de pacientes en tratamiento se asociaban los indicadores 7, 16, 20, 35, 38 y 40. Conclusion Se han identificado varios indicadores de calidad que pueden estar relacionados con ingreso hospitalario y mortalidad. Estos indicadores hacen referencia fundamentalmente al retraso diagnostico, seguimiento regular, prevencion de las infecciones y control de comorbilidades.

Introduction In 2010, the AIDS Study Group (Grupo de Estudio del SIDA [GESIDA]) developed 66 quality care indicators. The aim of this study is to determine which of these indicators are associated with mortality and hospital admission, and to perform a preliminary assessment of a prediction rule for mortality and hospital admission in patients on treatment and follow-up. Methods A retrospective cohort study was conducted in the Hospital Universitario Son Espases (Palma de Mallorca, Spain). Eligible participants were patients with human immunodeficiency syndrome ≥18 years old who began follow-up in the Infectious Disease Section between 1 January 2000 and 31 December 2012. A descriptive analysis was performed to evaluate anthropometric variables, and a logistic regression analysis to assess the association between GESIDA indicators and mortality/admission. The mortality probability model was built using logistic regression. Results A total of 1944 adults were eligible (median age: 37 years old, 78.8% male). In the multivariate analysis, the quality of care indicators associated with mortality in the follow-up patient group were the items 7, 16 and 20, and in the group of patients on treatment were 7, 16, 20, 35, and 38. The quality of care indicators associated with hospital admissions in the follow-up patients group was the same as those in the mortality analysis, plus number 31. In the treatment group the associated quality of care indicators were items 7, 16, 20, 35, 38, and 40. Conclusions Some GeSIDA quality of care indicators were associated with mortality and/or hospital admissions. These indicators are associated with delayed diagnosis, regular monitoring, prevention of infections, and control of comorbidities.

Introduction Previous studies have reported that the rate of FEV1 decline over time is increased in HIV patients but the mechanisms underlying this observation are unclear. Since current HIV treatment with Highly Active Antiretroviral Therapy (HAART) results in very good immuneviral control, we hypothesized that HAART should normalize the elevated rate of FEV1 decline previously reported in HIV patients if it was somehow related to the immune alterations caused by HIV, particularly in never smokers or quitters, since smoking is a well established risk factor for accelerated FEV1 decline in the general population. Methods We explored this hypothesis in a prospectively recruited cohort of 188 HIV (smoker and non-smoker) patients treated with HAART in Palma de Mallorca (Spain) and followed-up for 6 years. The cross-sectional characteristics of this cohort have been published elsewhere. Results We found that: (1) HAART resulted in good immune-viral control; (2) the rate of FEV1 decline remained abnormally elevated, even in non-smokers and quitters; and, (3) alcohol abuse during follow-up was related to FEV1 decline in these patients. Discussion Despite adequate immune-viral control by HAART, lung function decline remains increased in most HIV patients, even in non-smokers and quitters. Alcohol abuse is a preventable risk factor to decrease the accelerated FEV1 decline in this population., This work was financed through ABAMI (Balearic Association of Infectious Diseases).The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naive-HIV-infected patients. Methods We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience's MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value). Results All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028). Conclusions DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naive HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection., This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Accion Estrategica en Salud, Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (2013-2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdireccion General de Evaluacion) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigacion Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid B2017/BMD-3703. Programa de Investigacion de la Consejeria de Sanidad de la Comunidad de Madrid to JLJ. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by ISCIII with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 Cancer Nanomedicine from the Bench to the Bedside supported by COST (European Cooperation in Science and Technology). AFR and MAJS are supported by Instituto de Salud Carlos III [grant number CP14/0010 and CP17CIII/00007, respectivelly].

Background: Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART. Objectives: To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ART-naive patients in Spain. Methods: During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used. Results: Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/ lamivudine was 1.7%, 1.9% and 0.7%, respectively. Conclusions: Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.

Resumen Introduccion El objetivo del estudio es validar los indicadores de calidad relevantes para la infeccion VIH de GESIDA, evaluando la fiabilidad, la factibilidad y la adhesion a los mismos. Metodos La fiabilidad fue evaluada mediante la reproducibilidad de 6 indicadores en revision por pares, siendo el segundo observador una persona externa. La factibilidad y la medida del grado de cumplimiento de 22 indicadores se realizaron de forma fragmentada anual con recogida retrospectiva de la informacion a partir de bases de datos o de la historia clinica de los 9 hospitales participantes. Resultados La fiabilidad fue elevada con niveles de concordancia interobservador superiores al 95% en 5 de los 6 indicadores. La mediana de tiempo para realizar cada uno de los indicadores oscilo entre 5 y 600 min, pero pudieron ser obtenidos progresivamente de bases de datos especificas, lo que posibilita la obtencion automatizada de los mismos. En cuanto al cumplimiento de los indicadores, alcanzaron los estandares establecidos los relacionados con la evaluacion inicial de los pacientes, indicacion y adecuacion del TAR a las guias, adherencia al TAR y seguimiento en consultas o alcanzar CV indetectables en la semana 48 del TAR. Respecto a los indicadores de prevencion de infecciones oportunistas y control de comorbilidades, no se alcanzaron los estandares establecidos y se observo una heterogeneidad importante entre hospitales. Conclusion Los indicadores de calidad de infeccion VIH de GESIDA permiten medir de forma fiable y factible unos indicadores relevantes que deberian recoger todas las unidades que asisten a pacientes con infeccion por VIH.

Resumen Objetivo Este estudio analiza la frecuencia de las complicaciones postoperatorias tras la cirugia cardiaca, la incidencia del fracaso en el rescate (FR) y su relacion con la supervivencia. Metodos Desde enero del 2003 hasta diciembre del 2009, se intervinieron 2.750 pacientes adultos de cirugia cardiaca. Se analizaron 9 complicaciones postoperatorias. Para conocer las variables asociadas con alguna de estas complicaciones, se realizo analisis de regresion logistica multiple. La supervivencia se estimo mediante curvas de Kaplan-Meier y las complicaciones asociadas con la mortalidad se estimaron mediante regresion de Cox. Resultados La mortalidad hospitalaria fue 1,4% (IC del 95%, 1,01%-1,9%). La frecuencia de complicaciones postoperatorias fue del 38,5% (36,7%-40,4%) y el FR, 3,6% (2,5%-4,9%). La cirugia urgente (OR = 2,03, IC del 95%, 1,52-2,72), la insuficiencia renal cronica (OR = 1,50, IC del 95%, 1,25-1,80) y la edad ≥70 anos (OR = 1,42, IC del 95%, 1,20-1,68) fueron las variables que se asociaron con mas fuerza con las complicaciones seleccionadas. La supervivencia a los 5 anos fue del 93% en los pacientes sin complicaciones y el 83% en los pacientes con alguna de las complicaciones (p Conclusiones La incidencia de complicaciones postoperatorias en cirugia cardiaca oscila alrededor del 40% y aumenta la mortalidad hospitalaria aunque el FR fue muy bajo (3,6%; IC del 95%, 2,5-4,9).

Background: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique that provides in vivo microscopic imaging of the distal lung. We hypothesized that the intra-alveolar exudates characterizing Pneumocystis jirovecii pneumonia (PJP) can be identified by pCLE in vivo and help in its diagnosis. Objectives: We aimed to assess the usefulness of pCLE for the in vivo diagnosis of PJP. Methods: Thirty-two human immunodeficiency virus (HIV)-positive patients with new pulmonary infiltrates and fever were studied using pCLE. Real-time alveolar images were recorded during the bronchoscopy for off-line analysis by two independent observers. Bronchoalveolar lavage samples were also obtained and processed for microbiology and cytological evaluation, including Grocott stain for P. jirovecii. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of pCLE for the diagnosis of PJP in these patients were calculated. Results: Fourteen patients (44%) were confirmed to have PJP by cultures/staining. pCLE was well tolerated in all patients. It identified intra-alveolar exudates in 13 of them (41%), where 11 of them (85%) had positive Grocott stain for P. jirovecci, with 93% concordance between observers. Sensitivity, specificity, PPV and NPV of pCLE for the diagnosis of PJP were 79, 89, 85 and 84%, respectively. In smokers, these figures improved to be 92, 88, 85 and 94%. Conclusions: pCLE is a quick and safe procedure for on-site diagnosis of PJP in HIV+ patients with excellent specificity and sensitivity mainly in smokers.

Objective To assess the awareness, knowledge, use, and willingness to use and need of PrEP among men who have sex with men (MSM) and transgender women (TW) who attended World Gay Pride (WGP) 2017 in Madrid. Design and methods Online survey. Participants were recruited through gay-oriented dating apps and HIV Non-Governmental Organizations' social media. Inclusion criteria included being MSM or TW, age 18 years old or above, and having attended WGP in Madrid. Information regarding the participant's awareness and knowledge, use or willingness to use, and need for PrEP was collected, as well as sociodemographic characteristics. Participants were considered to be in need of PrEP if they met one of the following indication criteria: having practiced unprotected anal intercourse with more than 2 partners, having practiced chemsex, or having engaged in commercial sex-all in the preceding 6 months. Descriptive and multivariable analyses with logistic regression were conducted. Results 472 participants met the inclusion criteria and completed the questionnaire. The mean age was 38, 97.7% were MSM, 77% had a university education, and 85% were living in Spain, mostly in big cities. Overall, 64% of participants were aware of PrEP, but only 33% knew correctly what PrEP was. 67% of HIV-negative participants were willing to take PrEP, although only 5% were taking it during WGP, mostly due to lack of access. 43% of HIV-negative respondents met at least one PrEP indication criteria. For HIV-negative men living in Spain, university education and living in big cities was associated with PrEP awareness. Lower education level and meeting PrEP criteria was associated with willingness to use PrEP. Conclusions Our study shows that among MSM attending WGP 2017 in Madrid, there was limited PrEP awareness, low accuracy of PrEP knowledge, and a high need and willingness to use PrEP. Health authorities should strengthen existing preventive strategies and implement PrEP., This work has been supported by the Spanish Network of Excellence on HIV ((RIS) (RD16CIII/0002/) and CIBERESP.