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BackgroundWhile a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear.MethodsWe analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events.ResultsThe study included 4625 participants, of whom 4.3% experienced an SNAE during the follow-up period. A CD4/CD8 ratio ConclusionsOur results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio SummaryThis study found that a low CD4/CD8 ratio (

Background Dolutegravir-based dual therapies for treating people living with HIV (PLHIV) are strategies strongly recommended in several practice guidelines. The safety and efficacy combination of Dolutegravir (DTG) plus 3TC as a switching strategy in virologically suppressed patients was demonstrated in the TANGO study. Wide multicenter real life data supporting this treatment is needed. The aim of the current study was to describe the efficacy in terms of immunovirological outcomes in patients treated with this antiretroviral combination. Methods From November 1st 2020 to August 1st 2021, data from 1062 PLHIV collected from 13 Spanish institutions were recorded in a multicenter, retrospective study; After discarding cases in which relevant variables were missing, finally 694 cases underwent statistical analysis. Inclusion criteria were age >18 years, and to receive treatment with DTG/3TC as a switch strategy. Immunovirological impact of this strategy ( CD4+, CD8+ and CD4+/CD8+ cell count, as well as HIV plasma viral load through weeks 24, 48 and 96 of follow up) was evaluated using multivariable mixed models where the individual was considered as a random effect. Sex and age were added as demographic covariables. Results 78% of patients were men, 16% had been previously diagnosed of AIDS. Mean age was 48 years old. Mean CD4 T cell count nadir was 300 cell/ml (160-480). We found a significant increase in CD4+ counts at 24, 48 and 96 weeks after switching drug strategy. We also detected a small increase in the CD4+/CD8+ count rate at 48 and 96 weeks. No significant change was found in CD8+ count. No differences were found on behalf of sex, between backbone drugs (73% switched from a TDF/FTC backbone and 26.9% from ABC/3TC) or amongst the different third agents used (62% switched from integrase inhibitors). We identified a strong and negative effect of having AIDS in the CD4+ count. However, this effect did not interact with the effect of switching drug strategies. CD4, CD8 and CD4/CD8 after switch at 24, 48 and 96w Log OR Conclusion PLHIV who, being virologically suppressed, switched to dual therapy based on DTG/3TC, experienced a statistically significant increase of CD4+ T cell count at weeks 24, 48 and 96, as well as an increase in CD4/CD8 T cell ratio, as well as high efficacy in terms of viral replication suppression, independently of the stage of HIV infection. Disclosures Luis Buzón-Martín, MD, ViiV, GILEAD, Jannsen, MSD: Lecture fees Carlos Dueñas Gutierrez, MD, ViIV, GILEAD, Jannsen, MSD: Lecture fees Jesús Troya, Staff, ViiV, GILEAD, Jannsen, MSD: Lecture fees.

Resumen Objetivos Analizar en la cohorte CoRIS las diferencias epidemiologicas y en la mortalidad entre mujeres y hombres que viven con VIH y su evolucion en el tiempo. Metodos Se compararon las variables de interes entre mujeres que viven con VIH y hombres que viven con VIH. Se realizo un analisis de tendencias usando la prueba de Mantel-Haenszel. Para estudiar la supervivencia se utilizaron las curvas de supervivencia de Kaplan Meier y un analisis de regresion de Cox. Resultados Se incluyeron un total de 10.469 personas, de las cuales 1.742 (16,6%) eran mujeres. En el momento de inclusion en la cohorte las mujeres que viven con VIH con respecto a los hombres que viven con VIH tenian un mayor porcentaje de transmisiones por el uso de drogas intravenosas (UDI), coinfeccion por el virus de la hepatitis C (VHC), estadio de sida y origen extranjero. Tambien presentaron una peor situacion inmunovirologica y nivel de estudios. Estas diferencias se mantuvieron en el estudio de tendencias. En cuanto a la edad, las mujeres que se incluyeron en la cohorte fueron cada vez mas mayores, y lo contrario sucedio con los hombres. En el analisis comparativo entre mujeres segun su lugar de origen encontramos mujeres mas mayores, con mas transmision por UDI y coinfeccion por VHC en el grupo de las mujeres que viven con VIH espanolas; en cambio, la infeccion por sifilis fue mas frecuente entre las nacidas fuera de Espana. No hubo grandes diferencias en relacion con otras caracteristicas, como el nivel de estudios o la situacion de enfermedad. El sexo no fue un condicionante de supervivencia, y si lo fueron factores que se asociaban mas a las mujeres. Conclusiones Las mujeres infectadas por el VIH se presentaron al diagnostico con unas caracteristicas epidemiologicas y asociadas a la infeccion por VIH que las hacen mas vulnerables, y estas tendencias fueron acentuandose o no mejoraron durante los anos de observacion.

The aim of this study was to examine the impact of late presentation (CD4+ cell count350 cells/μl or an AIDS-defining event) on effectiveness and safety of initial antiretroviral therapy (ART) and to evaluate whether treatment response depends on first-line ART regimen in late presenters.ART-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting triple ART between 2010 and 2018.We used multivariable models to assess differences in viral suppression (viral load50 copies/ml), immunological response (change in CD4+ cell count, CD4% (29%) and CD4/CD8 normalization (0.4 and1) multiple T-cell marker recovery (MTMR): CD4+ cell count more than 500 cells/μl and CD4%29% and CD4/CD81), and treatment discontinuation due to adverse events (TDAE) at 48 weeks from ART initiation.Out of 8002 participants, 48.7% were late presenters. Of them, 45.8% initiated ART with a NNRTI- (mostly TDF/FTC/EFV), 33.9% with a protease inhibitor (mostly TDF/FTC+boosted DRV) and 20.3% with an INI-based regimen (mostly ABC/3TC/DTG). At 48 weeks, late presenters had similar viral suppression, but worse immunological response, than non-late presenters with no difference on TDAE. Late presenters initiating with NNRTI-based regimens were more likely to achieve viral suppression than those starting with INI-based, due to the higher chance of achieving viral suppression observed with TDF/FTC/RPV compared to ABC/3TC/DTG. Initial treatment with NNRTI or protease inhibitor based showed similar immunological response than the INI-based regimens, which showed lower rates of TDAE than NNRTI- and protease inhibitor based regimens.Despite safety and effectiveness of initial ART in terms of viral suppression, late presenters may not experience complete immunological response. In late presenters, effectiveness and safety depends on both the class and the specific first-line ART regimen.

Background: HIV/AIDS progression is linked to vitamin D, which is regulated by several key cytochromes P450 (CYP). Single nucleotide polymorphisms (SNPs) in CYP genes influence vitamin D metabolism and serum levels. The objective of this study was to evaluate the association between CYP SNPs and the clinical AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients. Methods: We performed a retrospective study in 661 ART-naïve HIV-infected patients who were stratified by their AIDS progression pattern [181 long-term nonprogressors (LTNPs), 332 moderate progressors, and 148 rapid progressors (RPs)]. Four CYP SNPs (CYP2R1 rs10500804, CYP2R1 rs1993116, CYP27B1 rs10877012, and CYP24A1 rs6013897) were genotyped using Agena Bioscience's MassARRAY platform. Correction for multiple testing was performed using the false discovery rate (Benjamini-Hochberg procedure). Results: The adjusted regression showed a significant association only for CYP27B1 rs10877012 SNP. When analyzing all HIV patients, the rs10877012 T allele was protective against AIDS progression (ordinal outcome) under the dominant [adjusted odds ratio (aOR) = 0.69; P = 0.021) and additive (aOR) = 0.75; P = 0.025] inheritance models. When analyzing LTNPs versus RPs, the rs10877012 T allele also showed a significant protective association under the dominant (aOR = 0.45; P = 0.004) and additive (aOR = 0.54; P = 0.008) inheritance models. P values remained significant after correcting by multiple comparisons only for the comparison of LTNPs versus RPs (extreme phenotypes). Conclusions: The CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients. The rs10877012 SNP seems to have an impact on the clinical AIDS progression, possibly modifying vitamin D levels, which could be relevant for the pathogenesis of HIV infection. This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (2013-2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdirección General de Evaluación) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigación Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid (B2017/BMD-3703). CIBER-BBN is an initiative funded by the VINational 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 CP14/0010and CP17CIII/00007, respectivelly].Programa de Investigación de la Consejería de Sanidad de la Comunidad de Madrid to JLJ. Sí

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.

In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

Background The positive-intraoperative-cultures-type prosthetic joint infection (PIOC-PJI) is considered when surgical cultures yield microorganisms in presumed aseptic arthroplasty revisions. Herein we assess the risk factors for failure in the largest cohort of PIOC-PJI patients reported to date. Methods A retrospective, observational, multicenter study was performed during 2007–2017. Surgeries leading to diagnose PIOC-PJI included only one-stage procedures with either complete or partial prosthesis revision. Failure was defined as recurrence caused by the same microorganism. Results 203 cases were included (age 72 years, 52% females). Coagulase-negative staphylococci (n = 125, 62%) was the main etiology, but some episodes were caused by virulent bacteria (n = 51, 25%). Prosthesis complete and partial revision was performed in 93 (46%) and 110 (54%) cases, respectively. After a median of 3.4 years, failure occurred in 17 episodes (8.4%, 95%CI 5.3–13.1). Partial revision was an independent predictor of failure (HR 3.63; 95%CI 1.03–12.8), adjusted for gram-negative bacilli (GNB) infection (HR 2.68; 95%CI 0.91–7.89) and chronic renal impairment (HR 2.40; 95%CI 0.90–6.44). Treatment with biofilm-active antibiotics (rifampin/fluoroquinolones) had a favorable impact on infections caused by staphylococci and GNB. Conclusion Overall prognosis of PIOC-PJI is good, but close follow-up is required in cases of partial revision and in infections caused by GNB.

Introduction Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. Methods YWVH under suppressive ART were included and compared to a group of HIV‐negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. Results Thirty‐two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4‐ and CD8‐T cells showed high levels of activation (HLA‐DR/CD38), IL‐7 receptor expression (CD127) and exhaustion (TIM‐3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T‐cell activation (HLA‐DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD‐1) levels with the CD4/CD8 ratio among YWVH. HLA‐DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16high NK‐cell subsets, exhaustion T‐cell levels (CD57, TIM3) and NK cells activation levels. Conclusions Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice.

Introduction: Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation. Methods: This was a nested study in the Spanish AIDS Research Network. We selected HIV-infected ART-naive patients initiating 3DR who achieved viral suppression in the first 48 weeks of ART and either remained on 3DR during their follow-up or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory predictors of mortality during virologic suppression using multivariate piecewise mixed models. Findings: We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG). Interpretation: In this observational study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term anti-inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation. Funding: This work was supported by Instituto de Salud Carlos III, co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF) (AC17/00019, PI18/00154, COV20/00349, ICI20/00058, the Spanish AIDS Research Network RD16/0025/0001project), and Gilead Sciences (Investigator sponsored research 17- 10192). Declaration of Interest: Outside the submitted work, S. S.-V. reports personal fees from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD as well as non-financial support from ViiV Healthcare and Gilead Sciences and research grants from MSD and Gilead Sciences. J.M.-S. non-financial support from ViiV Healthcare, non-financial support from Jannsen Cilag, non-financial support from Gilead Sciences, outside the submitted work. J.P. reports grants from Instituto de Salud Carlos III during the conduct of the study; grants and personal fees from Gilead Sciences, personal fees from Janssen Cilag, personal fees from ViiV Health Care, personal fees from MSD, outside the submitted work. S.M. reports grants, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Gilead, outside the submitted work. There are no potential conflicts of interest. Ethical Approval: The Institutional Review Boards of the Carlos III Health Institute located in Madrid, Spain, the Ethics Committee at University Hospital Ramon y Cajal approved the study (ceic.hrc@salud.madrid.org, approval number 133-17).

© 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).

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM", Objectives: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). Methods: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. Results: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9–10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41–3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26–0.94, p 0.031). Conclusions: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH., This work was supported by the Instituto de Salud Carlos III (ISCII) (grant number COV20/00108) and the Spanish AIDS Research Network (RD16/0025), which is included in the Spanish I þ D þ I Plan and is co-funded by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER).

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains. This work was funded through Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, projects “Estudios sobre vigilancia epidemiológica molecular del VIH- 1 en España,” PI16CIII/00033, and “Epidemiología molecular del VIH-1 en España y su utilidad para investigaciones biológicas y en vacunas”, PI19CIII/00042; Red de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Subdirección General de Evaluación y Fondo Europeo de Desarrollo Regional (FEDER), Plan Nacional I + D + I, project RD16ISCIII/0002/0004; and scientific agreement with Osakidetza-Servicio Vasco de Salud, Government of Basque Country, MVI 1001/16. JC was supported by the Social European Fund through the Youth Employment Operational Program and the Youth Employment Initiative and by the Comunidad de Madrid. Sí

espanolIntroduccion. La infeccion por Clostridioides difficile (ICD) esta asociada a un aumento de la estancia hospitalaria y de la mortalidad y a una alta probabilidad de reingreso, lo que conlleva un aumento de uso de recursos sanitarios y por tanto un incremento de costes. El objetivo del estudio fue estimar la carga economica de la ICD recurrente (ICDr). Material y metodos. Estudio observacional, retrospectivo y multicentrico. Se incluyeron pacientes adultos (≥18 anos), que tuvieran registrado al menos un episodio diagnostico confirmado (primario o secundario) de ICDr durante enero 2010 y mayo 2018. El uso de recursos relacionado con la ICDr incluyo la estancia hospitalaria (urgencias previas, planta, aislamiento y UCI), asi como pruebas y tratamientos. Para episodios que ingresaron por ICDr (diagnostico principal) se considero la estancia completa registrada. Cuando la ICDr se registro como diagnostico secundario se estimo la estancia hospitalaria debida a ICDr mediante emparejamiento (1:1) utilizando la tecnica “propensity score”. Se consideraron como controles (episodios sin ICD) las hospitalizaciones registradas en Conjunto Minimo Basico de las Altas Hospitalarias. El coste total se calculo multiplicando las unidades naturales de los recursos por el coste unitario correspondiente. Todos los costes fueron actualizados a euros de 2019. Resultados. Se incluyeron 282 episodios ICDr (188 como diagnostico principal): 66,31% de los pacientes tenian mas de 65 anos y 57,80% eran mujeres. La estancia media (DE) hospitalaria fue de 17,18 (23,27) dias. Un 86,17% de los episodios fueron aislados debido a ICDr con una media (DE) de 10,30 (9,97) dias. El coste medio (IC-95%) total por episodio fue de 10.877€ (9.499-12.777), siendo la duracion de la estancia hospitalaria el 92,56% del coste total. Conclusiones. Tanto el uso de recursos como el coste debido a la ICDr tienen un alto impacto para el sistema nacional de salud lo que pone de relieve la importancia de prevenir las ICDr. EnglishSTRACT Introduction. Clostridioides difficile infection (CDI) is associated with increased hospital stays and mortality and a high likelihood of rehospitalization, leading to increased health resource use and costs. The objective was to estimate the economic burden of recurrent CDI (rCDI). Material and methods. Observational, retrospective study carried out in six hospitals. Adults aged ≥18 years with ≥1 confirmed diagnosis (primary or secondary) of rCDI between January 2010 and May 2018 were included. rCDI-related resource use included days of hospital stay (emergency room, ward, isolation and ICU), tests and treatments. For patients with primary diagnosis of rCDI, the complete hospital stay was attributed to rCDI. When diagnosis of rCDI was secondary, hospital stay attributed to rCDI was estimated using 1:1 propensity score matching as the difference in hospital stay compared to controls. Controls were hospitalizations without CDI recorded in the Spanish National Hospital Discharge Database. The cost was calculated by multiplying the natural resource units by the unit cost. Costs (euros) were updated to 2019. Results. We included 282 rCDI episodes (188 as primary diagnosis): 66.31% of patients were aged ≥65 years and 57.80% were female. The mean hospital stay (SD) was 17.18 (23.27) days: 86.17% of rCDI episodes were isolated for a mean (SD) of 10.30 (9.97) days. The total mean cost (95%-CI) per episode was €10,877 (9,499-12,777), of which the hospital stay accounted for 92.56% Conclusions. There is high cost and resource use associated with rCDI, highlighting the importance of preventing rCDI to the Spanish National Health System.

The World Health Organization recommends routinely screening HIV-infected patients with CD4We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114.The CrAg+ prevalence among HIV-infected patients with CD4

This study sought to analyse differences in epidemiology and survival between women and men living with HIV in the CoRIS cohort and the course of their disease over a 10-year period.Variables of interest between women living with HIV and men living with HIV were compared. A trend analysis was performed using the Mantel-Haenszel test. Kaplan-Meier survival curves and a Cox regression analysis were used to study survival.A total of 10,469 people were enrolled; of them, 1,742 (16.6%) were women. At the time of enrolment in the cohort, women living with HIV, compared to men living with HIV, had higher rates of transmission due to intravenous drug use (IDU), hepatitisC virus (HCV) coinfection, AIDS-stage disease and foreign origin. They also had a worse immunovirological status and a lower educational level. These differences were maintained in the trend study. Regarding age, the women included in the cohort were older whereas the men were younger. In the comparative analysis between women according to place of origin, we found that the group of Spanish women living with HIV featured older women with higher rates of IDU transmission and HCV coinfection, whereas the group of women living with HIV born outside of Spain featured women with higher rates of syphilis infection. There were no major differences in relation to other characteristics such as educational level or disease status. Although sex was not a determinant of survival, conditions more prevalent in women were determinants of survival.HIV-infected women presented at diagnosis with certain epidemiological and HIV-associated characteristics that made them more vulnerable. These trends became more marked or did not improve during the years of observation.

GAMES Investigators., [Background] Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking., [Objectives] The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort., [Methods] This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses., [Results] Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse., [Conclusions] Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Introduction We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. Methods All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. Results Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1000 people-year. In addition to ageing and smoking, time on ART (OR 1.11; 95% CI 1.05–1.17) and PI use (OR 1.72; 95% CI 1.0–2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99–1.0; p = 0.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08–3.92) were associated with higher mortality. Conclusions Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

Resumen Introduccion Presentamos un estudio caso-control de tumores no definitorios de sida (TNDS) en una cohorte de pacientes infectados por el VIH en la que valoramos las tasas de incidencia, supervivencia y factores pronosticos de mortalidad. Metodos Se recogieron de forma prospectiva en 7 hospitales, los diagnosticos de TNDS realizados de 2007 a 2011, con seguimiento posterior hasta diciembre de 2013. Se seleccionaron de forma aleatoria un grupo control de 221 pacientes VIH sin diagnostico de cancer. Resultados Se diagnosticaron 221 TNDS en una cohorte inicial de 7.067 pacientes VIH. Los mas frecuentes: hepatocarcinoma 20,5%, pulmon 18,7%, cabeza y cuello 11,9% y anal 10,5%. La tasa de incidencia de desarrollo de TNDS fue de 7,84/1.000 pacientes-ano. Ademas de la edad y el tabaco, el tiempo en TAR (OR 1,11; IC 95% 1,05-1,17) y el uso de IP (OR 1,72; IC 95% 1,0-2,96) aumentaron el riesgo de desarrollar un TNDS. Durante el seguimiento fallecieron el 53,42%, con una mediana de supervivencia de 199,5 dias. En el analisis de los factores pronosticos de mortalidad, los valores bajos de CD4 en el momento del diagnostico del tumor (OR 0,99; IC 95% 0,99-1,0; p = 0,033) y el diagnostico previo de sida (OR 2,06; IC 95% 1,08-3,92) se asociaron con una mayor mortalidad. Conclusiones Los predictores de TNDS en nuestra cohorte fueron la edad, el consumo de tabaco, los linfocitos CD4 y el mayor tiempo en TAR. La mortalidad es alta, siendo factores de riesgo los CD4 bajos en el momento del diagnostico del TNDS y el diagnostico previo de sida.

Grupo GAMES. [ES] Fundamento y objetivos: La toxicidad renal de ciertos antibióticos (AB) es conocida. El objetivo de nuestro trabajo es conocer el posible efecto de los tratamientos AB en el desarrollo de insuficiencia renal (IR) en pacientes con endocarditis infecciosa (EI). Material y método: Recogida en un registro nacional multicéntrico de los datos referentes a la función renal, tanto previa como su deterioro si existiese, durante el tratamiento de las EI y relacionarlo con los posibles factores causantes, entre ellos los AB. Resultados: Entre 2008 y 2012 se han analizado 1.853 episodios de EI remitidos desde 26 centros españoles. De ellos, un 21,6% presentaban una alteración previa de la función renal. Desarrollaron IR de novo o un empeoramiento de la función renal previa un 38,7% de los casos. En aquellos pacientes que presentaban IR previa, el deterioro fue más frecuente (64 frente a 31,7%; p < 0,001). Globalmente los pacientes con IR tenían más edad (70,6 frente a 67 años; p < 0,01) y comorbilidades (índice de Charlson 5 frente a 4; p < 0,01), y la EI era por Staphylococcus aureus (32,1 frente a 16,5%; p < 0,01). El uso de AB potencialmente nefrotóxicos solo se asoció a IR en el grupo de pacientes sin IR previa (aminoglucósidos: OR = 1,47 [IC 95% 1,096-1,988], p = 0,010; aminoglucósidos-vancomicina: OR = 1,49 [IC 95% 1,069-2,09], p = 0,019]). Conclusiones: En pacientes sin IR previa, los AB nefrotóxicos se asocian a un deterioro de la función renal. En pacientes con IR previa al episodio de EI, el deterioro de renal fue más frecuente, pero parece estar más relacionado con la gravedad de la infección. [EN] Background and objectives: The possible renal toxicity of certain antibiotics (AB) is well known. The objective of our work is to know the possible effect of AB treatments in the development of renal failure (RF) in patients with infective endocarditis (IE). Material and method: Collection from a national multi-centre registry of collection on renal function, both prior and its impairment, if any, during the treatment of IE and in relation to possible causative factors, including the use of AB. Results: Between 2008 and 2012, 1,853 episodes of IE reported from 26 Spanish centres were analysed. Of these, 21.6% had prior RF. They developed new RF or impairment of renal function in 38.7% of the cases. In patients with prior RF, impairment was more frequent (64 vs. 31.7%, P < .001). Overall, patients with RF were older (70.6 vs. 67 years, P < .01), had more comorbidities (Charlson index 5 vs. 4, P < .01), and IE by Staphylococcus aureus (32.1 vs. 16.5%, P < .01). Potentially nephrotoxic AB use was only associated with RF in patients without prior RF (aminoglycosides: OR = 1.47 [95% CI 1.096-1.988], P = .010; aminoglycosides with vancomycin: OR = 1.49 [95% CI 1.069-2.09], P = .019). Conclusions: In patients without prior RF, the use of nephrotoxic AB is associated with impairment of renal function. In patients with RF prior to the IE episode, impairment of renal function was more frequent but appears to be more related to the severity of infection.

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.

Recognition of potentially modifiable mechanisms implicated in the pathogenesis of non-AIDS events (NAEs) might help improve outcomes of HIV-infected individuals. HIV infection has been associated with increased oxidative stress. We assessed the association between F2-isoprostanes and serious NAEs, and whether they improve the predictive performance of inflammation and coagulation biomarkers.Prospective multicenter cohort. Individuals who had an incident serious NAE and 2 sex- and age-matched participants with no events were selected. Measurement of F2-isoprostanes, highly sensitive C-reactive protein, interleukin-6, D-dimer, sCD14, sCD40, sCD163, and neopterin levels was performed in successive plasma samples collected from cohort inclusion.Biomarkers were measured in 78 participants developing serious NAEs or death, and 151 subjects with no events. Adjusted levels of F2-isoprostanes, and also of highly sensitive C-reactive protein, sCD14, and D-dimer were higher in individuals who developed serious NAEs, including or not non-AIDS deaths. The same results were observed when only samples collected since the time of achieving virological suppression were analyzed. The additive incorporation of each biomarker, ending with F2-isoprostanes, in an adjusted model was associated with a graded and significant increase in the quality of model fitting, and 94% sensitivity, 33% specificity, and 0.77 accuracy to predict serious NAEs including non-AIDS-related death.Oxidative stress is associated with a higher risk of serious NAEs, including non-AIDS deaths. This effect is independent and additive to biomarkers of inflammation, monocyte activation, and coagulation. Our results suggest that oxidative stress should be included among mechanisms to deal with to improve prognosis of HIV-infected individuals.

Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. Patients and Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en Espana [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL

[EN] This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017.1 The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisions. The main difference with respect to the previous document concerns recommended initial ART regimens, only three of which are maintained as preferential. All three include dolutegravir or raltegravir, together with emtricitabine/tenofovir alafenamide or abacavir/lamivudine. Other differences concern the section on switching ART in patients with suppressed viral replication, which now includes new two- and three-drug regimens, and the antiretroviral drugs recommended for pregnant women and patients with tuberculosis. A recommendation has also been added for patients who present with acute HIV infection after pre-exposure prophylaxis., [ES] Esta actualización del documento sobre el tratamiento antirretroviral (TAR) en adultos que GeSIDA y el PNS elaboran desde hace 2 décadas, reemplaza a la de 20171. Su objetivo es proporcionar a los clínicos que tratan a adultos con infección por el VIH-1 recomendaciones basadas en evidencias científicas para guiar sus decisiones terapéuticas. El principal cambio respecto al documento previo incumbe a los regímenes recomendados para el TAR de inicio, solo 3 de los cuales se mantienen como preferentes, incluyendo todos ellos dolutegravir o raltegravir junto con emtricitabina/tenofovir alafenamida o abacavir/lamivudina. Otros cambios conciernen al apartado de cambio del TAR en pacientes con replicación viral suprimida, en el que se han incluido nuevos regímenes de 2 y 3 fármacos, y a los antirretrovirales recomendados en embarazadas o en pacientes con tuberculosis. Se ha añadido también una recomendación para personas que habiendo realizado profilaxis pre-exposición al VIH presentan una infección aguda por dicho virus.

Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with sero-negative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and –A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads, Instituto de Salud Carlos III from the Spanish Ministry of Health, through Red Temática de Investigación Cooperativa en SIDA (RIS) [G03/173(2), PI050528 and RD06/0006/0033 to MDV, RD06/0006/0035 and RD12/0017/0037 to the HIV BioBank, and C03/173 and RD12/0017/0018 to CoRIS], cofinanced by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER), and also financed by Plan Nacional I+D+I from the Spanish Ministry of Science and Technology [SAF2007-60934, SAF2010-18917 and SAF2013-48754-C2-1-R to MDV], by Instituto de Salud Carlos III [Intrasalud PI12/0056 to JA] and by Fundación para la Investigación y Prevención del SIDA en España (FIPSE) [to HIV Biobank]. Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO

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.

[Background]: The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. [Methods]: Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load

This work was aimed to study the HIV-1 subtype B epidemics in the Basque Country, Spain. 1727 HIV-1 subtype B sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled between 2001 and 2008, were analyzed. 156 transmission clusters were detected by means of phylogenetic analyses. Most of them comprised less than 4 individuals and, in total, they included 441 patients. Six clusters comprised 10 or more patients and were further analyzed in order to study their origin and diversification. Four clusters included men who had unprotected homosexual sex (MSM), one group was formed by intravenous drug users (IDUs), and another included both IDUs and people infected through unprotected heterosexual sex (HTs). Most of these clusters originated from the mid-1980s to the mid-1990s. Only one cluster, formed by MSM, originated after 2000. The time between infections was significantly lower in MSM groups than in those containing IDUs (P-value < 0.0001). Nucleoside RT and non-nucleoside RT inhibitor (NRTI and NNRTI)-resistance mutations to antiretroviral treatment were found in these six clusters except the most recent MSM group, but only the IDU clusters presented protease inhibitor (PI)-resistance mutations. The most prevalent mutations for each inhibitor class were PI L90M, NRTI T215D/Y/F, and NNRTI K103N, which were also among the most prevalent resistant variants in the whole dataset. In conclusion, while most infections occur as isolated introductions into the population, the number of infections found to be epidemiologically related within the Basque Country is significant. Public health control measures should be reinforced to prevent the further expansion of transmission clusters and resistant mutations occurring within them.

AIMS To compare patients who acquired HIV infection through use of injected drugs (HIV-IDU) with patients who acquired HIV by sexual transmission (HIV-ST) in terms of late presentation (LP), delay in anti-retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS. DESIGN Prospective multi-centre cohort study of HIV-infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS). SETTING Thirty-one centres from the Spanish public health-care system. PARTICIPANTS A total of 9355 patients were included (1064 HIV-IDU and 8291 HIV-ST) during 2004-13. MEASUREMENTS We compared LP (defined as presentation for care with a CD4 cell count

Post-exposure prophylaxis (PEP) can be a secondary measure to prevent infection by human immunodeficiency virus (HIV) when primary prevention has failed. PEP is advised for people with sporadic and exceptional risk exposure to HIV. This consensus document about occupational and non-occupational PEP recommendations aims to be a technical document for healthcare professionals. Its main objective is to facilitate the appropriate use of PEP. To this end, some recommendations have been established to assess the risk of transmission in different types of exposure, situations where PEP should be recommended, special circumstances to take into account, antiretroviral (ARV) guidelines including start and end of the treatment, early monitoring of tolerance and adherence to the treatment, subsequent monitoring of people exposed, independently of having received PEP or not, and need of psychological support. This document is intended for all professionals who work in clinical practice in the field of HIV infection.