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People with HIV (PWH) might have a higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes. Several scores were developed to predict COVID-19 progression to critical disease and are often used among PWH. We assessed the performance of two commonly used risk equations among PWH and COVID-19. Participants were identified from a multicenter cohort of 6,361 PWH on regular follow-up at 2 university hospitals. Of 99 HIV-infected individuals with confirmed SARS-CoV-2 infection, 63 had complete data and were included in this analysis. CALL and COVID-GRAM scores were calculated and participants were stratified into low-, intermediate-, and high-risk groups for each. Discrimination was assessed using receiver operating characteristic curves. Calibration was evaluated using observed versus expected (O:E) ratios and the Hosmer-Lemeshow χ

Sweet Syndrome (SS) belongs to a group of diseases known as neutrophilic dermatoses. An uncommon variant named Histiocytoid Sweet Syndrome (HSS) can be associated with a variety of conditions, including cancer, infections, drug toxicity and others. Here we present an instance of HSS in an HIV-positive patient in the setting of an infectious disease.

Background Low BMD (bone mineral density) has been described as a non–AIDS (Acquired Immune Deficiency Syndrome)-related event in HIV (human immunodeficiency virus)-patients but it is poorly studied in young HIV-infected men who have received no previous antiretroviral therapy. Methods A cross-sectional study of 245 naïve-HIV-infected men over 21 and under 50 years old who voluntary attended the Infectious Disease Division appointment in Hospital Fundación Jimenez Díaz in Madrid, from January 1st, 2014 to September 30th, 2017. All subjects underwent a baseline DXA scan (dual energy x-ray absorptiometry) performed prior to start antiretroviral treatment. Further, all patients who started treatment between May 1st and September 30th, 2017 were invited to participate in a substudy on bone mineral metabolism. All the information was collected through clinical history and complementary questionnaire. Results The mean age was 36.4 years, been 68% Caucasian, 29.3% Latin American and 2.7% African race. At the time of diagnosis, 91% of patients had stage-A (median CD4+ T-cell 481cells/μL, IQR, 320–659). 10% had a count below 200 CD4 cells/μL, and 40% had a CD4/CD8 cell-count-ratio below 0.4. Regarding lifestyle and risk factors, 14.1% presented underweight, 36.1% were not engage in any regular exercise, 51.9% were active smokers and 35.3% reported drug use. Low levels of vitamin D were seen in 87.6% of the study participants. Low BMD (Z-score Conclusions We find prevalence of increased bone involvement among naïve HIV-infected men under 50 years old. Further studies are necessary to evaluate if changes in actual guidelines are needed to assess BMD measurements in HIV-infected adult male patients under 50.

The choice of an optimal antiretroviral therapy (ART) in naive patients presenting late for initial therapy with advanced HIV infection, that is, with a CD4 cell count

Background Acute hepatitis C virus (AHC) infection is increasingly common among HIV+ men who have sex with men (MSM). Until 2017, the guidelines recommended therapy with pegylated-interferon plus ribavirin with a mild sustained virological response (SVR). This prompted many patients to reject that treatment, at that time, waiting to be treated with better and safer options with new Direct-Acting-Antivirals (DAA). Objectives Assess the efficacy and safety of Elbasvir/Grazoprevir to treat recent chronic hepatitis C infection, genotype 1 or 4, in HIV+ MSM patients. Methods Prospective, open-labeled, two center, pilot study. SVR is analyzed for treatment with Elbasvir/Grazoprevir (8 weeks in GT1b or 12 in GT1a or GT4) in patients with a recent chronic HCV infection, defined as HCV infection lasting less than 4 years and mild liver fibrosis (liver stiffness Results Forty-eight patients were included (May 2017–March 2018): 2 GT1b, 24 GT1a and 22 GT4. HCV-RNA > 800000 UI in 63% and medium liver stiffness 4.9 kPa. The SVR was 98%, one patient failed due to poor adherence. 67% of patients had adverse effects, but only 16% treatment related. The most frequent side effects were gastrointestinal (19%), related with the central nervous system (18%), respiratory (16%) and systemic symptoms (15%). During one year of follow-up post-therapy, 4 AHC and 18 patients with sexually transmitted diseases (STD) were diagnosed. Conclusions Treatment with Elbasvir/Grazoprevir in this scenario is highly effective and safe. Patients with risky sexual practices must remain linked to the medical care system to detect new STD and HCV reinfection.

Graphical Abstract, Highlights • Lower mortality rate was observed in HIV patients. • Similar hospitalization and ICU admission rate were observed in HIV patients. • Age and comorbidities also represent the main poor prognostic factors for PLHIV. • HIV severity or the type of antiretroviral does not influence the Covid-19 outcome., Objectives The information of how COVID-19 infection affects people living with HIV (PLHIV) is still scarce. Methods Observational study was conducted in four of public hospitals in Madrid. All HIV patients with confirmed or suspected COVID-19 disease were included and compared with COVID-19 infected patients without HIV infection. Results Sixty-three patients with HIV infection were analysed. The median age was 46 years (IQR: 37-56 years), 88.9% were men. The median time of HIV infection was 10.8 years (IQR: 6.5 - 16.8 years), 96.8% were on antiretroviral therapy. 84.1% had previous comorbidities. The most common symptoms were fever(66.1%), cough(66.1%) and dyspnea(46.8%). Pneumonia was found in 47.5%, 28.6% of patients had severe disease and 32.3% was admitted to hospital. The ICU admission rate and the mortality rate were both 3.17%. Significant association was observed between age, arterial hypertension, overweight, diabetes mellitus and the severity of COVID-19 disease. No association was observed between HIV-related factors. The rate of COVID-19 disease in HIV-patients was 1,68%. A similar hospitalization (31.74% vs 32.57%) and ICU admission rate (3.17% vs 2%) was observed with non-HIV infected patients. A lower mortality rate during hospitalization (10% vs 21.37%) and global mortality rate (3.17% vs 6.96%) were observed. Conclusions Established poor prognostic factors, such as age and comorbidities, represent also the main determinants for PLHIV. Neither the HIV severity, nor the type of ARV treatment seem to influence the outcome of COVID-19 infection. Large prospective cohorts are needed in order to establish the differences between HIV positive and negative patients.

Graphical abstract, Highlights • The survival rate is high (94% vs 72%) if tocilizumab is administered with a FiO2 ≤ 0.5%. • There are very limited side effects and secondary infections. • A significant decrease in the median serum ferritin and the median HSCRP was observed., Introduction Tocilizumab is an interleukin 6 receptor antagonist which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), aiming to ameliorate the cytokine release syndrome (CRS) -induced acute respiratory distress syndrome (ARDS). However, there are no consistent data whom might benefit most from it. Methods We provided tocilizumab on a compassionate-use basis to patients with SSP hospitalized (excluding intensive care and intubated cases) who required oxygen support to have a saturation >93%. Primary endpoint was intubation or death after 24 hours of its administration. Patients received at least one dose of 400 mg intravenous tocilizumab during March 8-2020, through April 20-2020. Results A total of 207 patients were studied and 186 analysed. The mean age was 65 years and 68% were male. A co-existing condition was present in 68 % of cases. Death prognostic factors were older age, higher IL-6, D-dimer and high sensitivity C reactive protein (HSCRP), lower total lymphocytes and severe disease requiring higher oxygen support. The primary endpoint (intubation or death) was significantly worst (37% vs 13%, p 0.5%). Conclusions Tocilizumab is well tolerated in patients with severe SARS-CoV-2 pneumonia, but it has a limited effect on the evolution of cases with high oxygen support needs.

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE®, Embase®, PubMed, Cochrane library, and relevant international conference proceedings from 2013 to 2020. Qualitative synthesis of virologic suppression at Week 48, treatment-emergent resistance, discontinuation rates, and comorbidities was undertaken, with no statistical analyses conducted. Linked publications and potential for duplication in reporting of outcomes for cohorts and populations were identified, and the publication reporting the highest number of PWH receiving dolutegravir plus lamivudine was included in the analysis. Thirty-four studies reporting on cohorts of PWH not suspected to be linked or to include duplicate data receiving dolutegravir plus lamivudine were identified (N = 5017). Of 3744 virologically suppressed PWH who switched to dolutegravir plus lamivudine, 603 (16%) reported history of virologic failure. Nineteen studies included effectiveness data (n = 3558), four of which included data from treatment-naive PWH (n = 69). In studies with > 100 PWH, high rates of virologic suppression (Week 48, 97–100%) were maintained with dolutegravir plus lamivudine, with low rates of virologic failure (0–3.3 per 100 person-years of follow-up); one instance of emergent integrase strand transfer inhibitor resistance was reported in a complex treatment-experienced individual. Rates of discontinuation due to adverse events were low and consistent with previously observed trial data. Dolutegravir plus lamivudine minimally impacted renal function and had minimal impact on or improved lipid profiles and bone mineral density. This systematic review demonstrates that effectiveness and safety of dolutegravir plus lamivudine in clinical practice support data from randomized controlled trials with regard to high rates of virologic response, low rates of discontinuation, and a high barrier to resistance. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00522-7.

Purpose: To describe the different phenotypes of syphilitic chorioretinitis (SCR) and its clinical features in multimodal imaging (MI).Methods: Complete ophthalmological examination and MI including spectral domain optic coherence tomography (SD-OCT), fundus autofluorescence (FAF) and fluorescein angiography (FA) were performed at diagnosis and during follow-up in patients diagnosed with SCR.Results: 17 eyes of 10 patients were included. Clinical phenotypes included acute syphilitic posterior placoid chorioretinopathy (ASPPC), syphilitic outer retinitis (SOR) and punctate inner retinitis (PIR). Disruption of outer retinal layers were visible in all patients in SD-OCT. Inner retinal layers were only affected in PIR. FAF revealed macular hyperautofluorescence in all patients. FA showed maintained hyperfluorescence in ASPPC and SOR.Conclusions: ASPPC, SOR and PIR are different phenotypes of syphilitic chorioretinitis and present common features in SD-OCT and FAF. MI provides useful information to help the clinician during diagnosis and follow-up of these entities.

Background: Bone alterations have been observed in the course of HIV infection, char-acterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibi-tors (NRTIs) in treatment-naïve HIV patients. Methods: We conducted a prospective study in naïve HIV-infected adults (under 50 years), separat-ed into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment. Results: Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/μL. At week 12 after starting treatment, both TDF [increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003)] and TAF [increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049)] presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences. Conclusion: Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks., This research was financially supported by The Carlos III Health Institute through the “Miguel Servet” program (CP15/00053), co-funded by The European Regional Development Fund and research grants from the Spanish Carlos III Health Institute (PI16/00991 and PI19/00744)

Objective Currently, there are no definitive data on the relationship between low levels of vitamin D in the blood and a more severe disease course, in terms of the need for hospital admission, intensive care unit (ICU) stay, and mortality, in patients with coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to study the association between levels of circulating 25-hydroxyvitamin D (25(OH)D) and adverse clinical outcomes linked to SARS-CoV-2 infection. We further aimed to observe the incidence of low, below-average, and normal levels of 25(OH)D in patients hospitalized for COVID-19 between March 12, 2020, and May 20, 2020, and assess whether these values differed between these patients and a normal population. Finally, we determined whether the need for transfer to the intensive care unit (ICU) and the mortality rate were related to low levels of 25(OH)D. Study Design Retrospective observational study Setting Quironsalud Hospitals in Madrid, Spain Participants We analyzed 1549 patients (mean age, 70 years; range, 21-104 years); 835 were male (53.9%; mean age, 73.02 years), and 714 were female (46.1%; mean age, 68.05 years). Subsequently, infected patients admitted to the ICU (n = 112) and those with a fatal outcome (n = 324) were analyzed. Procedures Serum concentrations of 25(OH)D were measured by electrochemiluminescence. Results More hospitalized patients (66%, n = 1017) had low baseline levels of 25(OH)D (

© 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.

Background While the microbiota has been associated with human papillomavirus malignant transformation, it is unclear whether anal bacteria could improve the low specificity of anal cytology for the screening of high-grade intraepithelial squamous neoplasia (HSIL) Methods We recruited men who have sex with men undergoing anal cytology and high-resolution anoscopy. We assessed the microbiota composition from fecal samples and cytobrush anal samples using 16S ribosomal DNA sequencing in participants with or without biopsy-proven HSIL (bHSIL). We selected bacterial biomarkers based on their linear discriminant analysis. We assessed their predictive performance using logistic regression and bootstrap resampling. Results We included 128 individuals, 47 (36.7%) with bHSIL and 99 (77.3%) with human immunodeficiency virus. We detected 40 potential predictors of bHSIL. Ruminococcaceae NK4A214 group, Alloprevotella genus, Prevotella melanonigenica, and Ruminococcaceae UCG-014 were the most predictive of bHSIL. From 35 false-positive cytologic results, the combination of these 4 biomarkers with the anal cytology reclassified to true-negative 33 individuals (94%) and showed good diagnostic performance (area under the receiver operating characteristic curve, 0.805; 95% confidence interval, .728–.882). Conclusions We found anal-associated bacteria indicative of a higher risk of precancerous anal lesions, which combination was highly specific. The microbiota could be developed as a complementary diagnostic tool to overcome the limitations of the current screening strategy for anal cancer.

Background: Low bone mineral density has been described as a non–AIDS (Acquired Immune Deficiency Syndrome)-related event in HIV (human immunodeficiency virus)-patients but it is poorly studied in young HIV-infected men who have received no previous antiretroviral therapy.Methods: A cross-sectional study of 245 naïve-HIV-infected men over 21 and under 50 years old was carried out between January 2014 and September 2017. Results: The mean age was 36.4 years, been 68% Caucasian and 29.3% Latin American. At the time of diagnosis, 91% of patients had stage-A (median CD4+ T-cell 481cells/μL, IQR, 320–659). 10% had a count below 200 CD4 cells/μL, and 40% had a CD4/CD8 cell-count-ratio below 0.4. Regarding lifestyle and risk factors, 14.1% presented underweight, 36.1% engaged in no regular exercise, 51.9% had previous exposure to tobacco and 35.3% reported drug use. Low levels of vitamin D were seen in 87.6% of the men studied. Low BMD (Z-scoreConclusions: We find prevalence of bone involvement among naïve HIV-infected men under 50 years old. Further studies are necessary to evaluate if BMD assessment should be recommended in young HIV-infected patients.

Objective: The source of residual HIV viremia is highly debated and its potential relationship with the HIV reservoir has not been clarified. Herein, we analysed the cell-associated HIV-DNA content in two important cell compartments of the HIV reservoir, resting CD4þ T memory (Trm) and peripheral T follicular helper (pTfh) cells, and the association with the residual HIV viremia in individuals with spontaneous HIV replication control (elite controllers, EC group) and in individuals with antiretroviral therapy (ART)-mediated HIV replication control (cART group). Design: A cross-sectional study. Methods: Seventeen chronically HIV-infected patients with suppressed HIV replication were included. Cell-associated HIV-DNA was measured by ultrasensitive digital-droplet-PCR in purified Trm and pTfh cells. Residual HIV plasma viremia was quantified using a single-copy assay with a sensitivity of 0.3 HIV-RNA copies/ml. Results: A significant and positive correlation was demonstrated between HIV-DNA levels in pTfh cells and residual plasma viral load (rpVL) (rho ¼ 0.928, P ¼ 0.008) in HIV-positive elite controllers, but not in HIV-positive treated patients, despite the lower levels of cell-associated HIV-DNA found in elite controllers compared with cART patients in pTfh cells [176 (77–882) vs. 608 (361–860) copies/million cells, respectively; P ¼ 0.05]. Conclusion: This association suggests that pTfh cells could have an important contribution to persistent viremia in elite controllers. This could be the consequence of a more limited control of HIV replication in elite controllers with higher transcriptional activity of HIV in pTfh cells of elite controllers than that in cART patients.

(1) Background: The role of hepatitis C virus (HCV) co-infection on the T-cell homeostasis disturbances in human immunodeficiency virus (HIV)-infected patients as well as its reversion after HCV eradication with direct acting antivirals (DAAs) therapy has not been yet clarified. We extensively analyzed the effect of HCV co-infection on immune parameters of HIV pathogenesis and its evolution after HCV eradication with DAAs. (2) Methods: Seventy individuals were included in the study&mdash, 25 HIV-monoinfected patients, 25 HIV/HCV-coinfected patients and 20 HIV and HCV seronegative subjects. All patients were on antiretroviral therapy and undetectable HIV-viremia. Immune parameters, such as maturation, activation, apoptosis, senescence and exhaustion of T-cells were assessed by flow cytometry. Cross-sectional and longitudinal (comparing pre- and post-DAAs data in HIV/HCV coinfected patients) analyses were performed. Univariate and multivariate (general linear model and canonical discriminant analysis -CDA-) analyses were used to assess differences between groups. (3) Results&mdash, The CDA was able to clearly separate HIV/HCV coinfected from HIV-monoinfected patients, showing a more disturbed T-cells homeostasis in HIV/HCV patients, especially activation and exhaustion of T-cells. Interestingly, those perturbations were more marked in HIV/HCV patients with increased liver stiffness. Eradication of HCV with DAAs restored some but not all the T-cells homeostasis disturbances, with activation and exhaustion of effector CD8 T-cells remaining significantly increased three months after HCV eradication. (4) Conclusions&mdash, HCV co-infection significantly impacts on several immune markers of HIV pathogenesis, especially in patients with increased liver stiffness. Eradication of HCV with DAAs ameliorates but does not completely normalize these alterations. It is of utmost relevance to explore other mechanisms underlying the immune damage observed in HIV/HCV coinfected patients with control of both HIV and HCV replication.

Background Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial. Methods We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up. Results Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF. Conclusions Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF., This clinical trial demonstrates the reversibility of DTG/ABC/3TC-related neuropsychiatric adverse events after switching to another integrase inhibitor-based therapy in virologically suppressed HIV-infected individuals. These results have implications for our understanding of the neurotoxicity profile of dolutegravir and other integrase inhibitors.

Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these conditions. However, HCV can be eradicated in most patients with the new direct-acting antivirals (DAAs) therapy. We have analyzed the effect of HCV on systemic inflammation, endothelial activation and coagulopathy in PLWH and its evolution after HCV eradication with DAAs. Twenty-five HIV/HCV coinfected (HIV/HCV group), 25 HIV monoinfected (HIV group) and 20 healthy controls (HC) were included in the study. All patients were on ART and HIV suppressed. Levels of fourteen markers of systemic inflammation, endothelial activation and coagulopathy (IL-1&szlig, IL-6, IL-12p70, IL-8, TNF&alpha, D-dimer, Eotaxin, IL-18, IP-10, monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), TNF&alpha, receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)) were measured on plasma at baseline and after DAAs-mediated HCV eradication. Non-parametric tests were used to establish inter/intra-group differences. At baseline, the HIV/HCV group showed increased levels of IL-18 (p = 0.028), IP-10 (p &lt, 0.0001), VCAM-1 (p &lt, 0.0001) and ICAM-1 (p = 0.045), compared to the HC and HIV groups, with the highest levels for IL18 and IP10 observed in HIV/HCV patients with increased liver stiffness (&ge, 7.1 KPa). Eradication of HCV with DAAs-based therapy restored some but not all the evaluated parameters. VCAM-1 remained significantly increased compared to HC (p = 0.001), regardless of the level of basal liver stiffness in the HIV/HCV group, and IP-10 remained significantly increased only in the HIV/HCV group, with increased level of basal liver stiffness compared to the HC and to the HIV groups (p = 0.006 and p = 0.049, respectively). These data indicate that DAAs therapy in HIV/HCV co-infected patients and HCV eradication does not always lead to the normalization of systemic inflammation and endothelial dysfunction conditions, especially in cases with increased liver stiffness.

This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving antiretroviral therapy (ART). These findings warrant further investigation of HIV ART in HIV preexposure prophylaxis studies and randomized trials among persons without HIV., Visual Abstract. Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving ART This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving antiretroviral therapy (ART). These findings warrant further investigation of HIV ART in HIV preexposure prophylaxis studies and randomized trials among persons without HIV. Visual Abstract. Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving ART This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving antiretroviral therapy (ART). These findings warrant further investigation of HIV ART in HIV preexposure prophylaxis studies and randomized trials among persons without HIV., Background: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations. Objective: To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART. Design: Cohort study. Setting: HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020. Participants: 77 590 HIV-positive persons receiving ART. Measurements: Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction–confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models. Results: Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died. Limitation: Residual confounding by comorbid conditions cannot be completely excluded. Conclusion: HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV. Primary Funding Source: Instituto de Salud Carlos III and National Institutes of Health.

OBJECTIVES The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts

There is limited information describing features and outcomes of patients requiring hospitalization for COVID19 disease and still no treatments have clearly demonstrated efficacy. Demographics and clinical variables on admission, as well as laboratory markers and therapeutic interventions were extracted from electronic Clinical Records (eCR) in 4712 SARS-CoV2 infected patients attending 4 public Hospitals in Madrid. Patients were stratified according to age and stage of severity. Using multivariate logistic regression analysis, cut-off points that best discriminated mortality were obtained for each of the studied variables. Principal components analysis and a neural network (NN) algorithm were applied.A high mortality incidence associated to age >70, comorbidities (hypertension, neurological disorders and diabetes), altered vitals such as fever, heart rhythm disturbances or elevated systolic blood pressure, and alterations in several laboratory tests. Remarkably, analysis of therapeutic options either taken individually or in combination drew a universal relationship between the use of Cyclosporine A and better outcomes as also a benefit of tocilizumab and/or corticosteroids in critically ill patients.We present a large Spanish population-based study addressing factors influencing survival in current SARS CoV2 pandemic, with particular emphasis on the effectivity of treatments. In addition, we have generated an NN capable of identifying severity predictors of SARS CoV2. A rapid extraction and management of data protocol from eCR and artificial intelligence in-house implementations allowed us to perform almost real time monitoring of the outbreak evolution.

Plasma levels of adenosine deaminase (ADA), an enzyme that deaminates adenosine to inosine, are increased during inflammation. An increase in ADA activity occurs with lower human immunodeficiency virus (HIV) viral load and higher CD4+ T cell counts. We aimed to investigate the role of plasma ADA as a biomarker of inflammation in treatment-na&iuml, ve HIV patients who received tenofovir or another nucleoside analog for comparison. Ninety-two treatment-na&iuml, ve patients were included in the study and grouped by treatment, i.e., tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) or Triumeq. ADA activity was measured in plasma and cytokines were analyzed by MILLIPLEX&reg, MAP-Luminex&reg, Technology. Plasma concentration of monocytes and neutrophils was measured at 0, 3, and 12 months post-treatment. Treatment-na&iuml, ve HIV patients had increased ADA concentrations (over 15 U/L) that decreased after treatment with TAF and Triumeq, though this did not occur in TDF-treated patients. However, all groups exhibited a pro-inflammatory systemic profile at 12 months of treatment. Plasma GM-CSF levels decreased after 12 months of treatment in the TDF group, with a concomitant decrease in blood monocyte count, and a negative correlation with ADA values was found. In conclusion, ADA levels may be modulated by antiretroviral therapy in HIV patients, possibly affecting inflammatory status.

ObjectivesWe compared 48 week effectiveness and safety of first-line antiretroviral regimens.MethodsWe analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting the most commonly used antiretroviral regimens from 2014 to 2018. We used multivariable regression models to assess the impact of initial regimen on: (i) viral suppression (VS) (viral load 0.4 and >1); (iv) CD4 percentage normalization (>29%); (v) multiple T-cell marker recovery (MTMR: CD4 > 500 cells/mm3 plus CD4 percentage >29% plus CD4/CD8 > 1); (vi) lipid, creatinine and transaminase changes; and (vii) discontinuations due to adverse events (AE).ResultsAmong 3945 individuals analysed, the most frequently prescribed regimens were ABC/3TC/DTG (34.0%), TAF/FTC/EVG/CBT (17.2%), TDF/FTC + DTG (11.9%), TDF/FTC/EVG/CBT (11.7%), TDF/FTC/RPV (11.5%), TDF/FTC + bDRV (8.3%) and TDF/FTC + RAL (5.3%). At 48 weeks, 89.7% of individuals achieved VS with no significant differences by initial regimen. CD4 mean increase was 257.8 (249.3; 266.2) cells/mm3, and it was lower with TAF/FTC/EVG/CBT and TDF/FTC/RPV compared with ABC/3TC/DTG. CD4 percentage normalization was less likely with TAF/FTC/EVG/CBT, and MTMR was less likely with TAF/FTC/EVG/CBT and TDF/FTC + RAL. The proportion of discontinuations due to AE was higher with TDF/FTC + bDRV (9.7%), followed by TDF/FTC/EVG/CBT (9.5%) and TDF/FTC + DTG (7.9%). Compared with ABC/3TC/DTG, cholesterol and LDL mean increases were higher with TAF/FTC/EVG/CBT and lower with TDF/FTC + DTG, TDF/FTC/RPV and TDF/FTC + RAL. Higher mean increases in triglycerides were significantly associated with TAF/FTC/EVG/CBT. Regimens containing DTG showed higher creatinine increases.ConclusionsThe significantly greater immunological response and safety of some combinations may be useful for making decisions when initiating treatment.

© The Author(s) 2020., [Background]: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS)., [Methods]: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014–2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL), [Results]: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL, [Conclusions]: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads., The RIS cohort (CoRIS) is supported by the 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 and cofnanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER)”.

ObjectivesTo assess the attitudes and opinions about generic antiretroviral drugs (ARVs) and single-tablet regimen (STR) de-simplification among physicians prescribing HIV treatment in the cohort of the Spanish HIV/AIDS Research Network (CoRIS).MethodsAn online questionnaire with 27 structured questions was sent to all physicians (n = 199) who prescribed ARVs among the 45 centres participating in the cohort.ResultsA total of 169 (84.9%) physicians answered the questionnaire. Only 4.1% of the physicians would never prescribe generic ARVs, but 53.3% would not prescribe them if the number of pills per day increased and 89.3% would not prescribe them if the number of doses per day increased. However, 84.0% of the physicians agreed to prescribe generic ARVs if doing so would decrease costs for the public healthcare system. The percentages of physicians stating that generic ARVs (compared with branded ones) would be associated with worse adherence, more adverse effects or more probability of virological failure, provided that the number of pills and doses per day would not change, were low: 0.6%, 7.7% and 3.6%, respectively. However, these percentages were much higher if the generic ARV entailed breaking an STR: 63.9%, 18.9% and 42.0%, respectively. Most physicians stated that they needed more information about the effectiveness and safety of generic ARVs and the price difference compared with their branded equivalents.ConclusionsAlthough most physicians were confident about prescribing generic ARVs, the majority had strong concerns about de-simplifying STR, and they also needed more information about generic drugs.

BIRDi study group., The use of two potent, well-tolerated, drugs could permit the maintenance of virologic suppression even in heavily pretreated people living with HIV. In this retrospective, multicenter, simplification study (NCT03348449), we included those patients with virologic suppression who switched to raltegravir (RAL) plus boosted darunavir (b/DRV). Overall, 345 patients (75 females, 25%) were included. Patients were largely pretreated (mean, 9.4 regimens), suppressed for a median of 41.1 months. Fifty patients had ≥1 mutation against DRV. At 96 weeks, the efficacy by intention-to-treat analysis (snapshot) was 73% (95%CI, 68.4–77.8%), but 97.1% (95%CI, 95.4–98.9) excluding changes due to non-virologic reasons, and virologic failure was rare (0.9%; 95%CI, 0.1–1.2%). Median CD4/CD8 ratio increased from 0.59 to 0.62 (p

Clinicians sometimes use switching strategies based on regimens such as RAL + ABC/3TC or RPV + ABC/3TC in order to resolve tolerability or safety issues associated with conventional recommended first-line strategies. Despite the low genetic barrier of these regimens, high safety and efficacy rates have been reported in retrospective studies.

Introduction Cutaneous anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis, which typically presents with ulcers after contact with animals or animal products, and is rarely seen in high-income countries but is common in those with low- and middle-incomes. Objective. The aim of this study is to show the main clinical characteristics of cutaneous anthrax in endemic areas. Material and methods The study describes the main clinical characteristics of cutaneous anthrax in eight patients (six female and two male, age range 1 - 56 years) admitted to the rural General Hospital of Gambo, West Arsi Province of Ethiopia from 2010-2013. Results In all cases, lesions began as an erythematous papule located on exposed sites (n=7 head; n=1 thigh) and subsequently became a necrotic black eschar surrounded by an edematous halo. Two patients presented with painful ipsilateral adenopathy near the black eschar. Four patients developed a malignant pustule on the suborbital region of the face. Patients responded positively to treatment, and the lesions resolved, leaving eschars. However, one patient suffered the loss of an eyeball, and another died 12 hours after starting treatment. Conclusions Physicians working in rural areas of resource-poor settings should be trained in the clinical identification of cutaneous anthrax. Early antibiotic treatment is essential for decreasing morbidity and mortality.

Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy. The interdependence and roles of T cell-mediated immune responses and IL28B rs12979860 single-nucleotide polymorphism genotype as predictors of virological response to anti-HCV treatment in patients with chronic hepatitis C were evaluated using nonparametric tests. Factors associated with rapid virological response (RVR) in univariate analysis were presence of CD4 T cell response against NS3 HCV protein, low baseline HCV-RNA, and IL28B CC genotype. Factors associated with sustained virological response (SVR) in univariate analysis were IL28B CC genotype, low baseline HCV-RNA, and presence of CD4 response against NS2. In the multivariate analysis, low baseline HCV-RNA and NS3-specific CD4 response showed a clear trend toward association with RVR (P = 0.09 and P = 0.07, respectively). Regarding SVR, IL28B CC genotype was the strongest predictor (P = 0.02), with presence of NS2-specific CD4 response showing a clear trend (P = 0.09). HCV-specific T cell response influences the outcome of pegIFNα/RBV therapy regardless of IL28B genotype. HCV-specific T cell responses (adaptive immunity) seem to influence viral clearance both in the short and long term during therapy (RVR and SVR), whereas the influence of the IL28B genotype (innate immunity) may be more relevant to the long-lasting therapeutic effect (SVR).

[Objectives]: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004–2017., [Methods]: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models., [Results]: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL., [Conclusions]: The initial assessment of HIV‐infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations., The RIS cohort (CoRIS) is supported by the 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 and cofinanced by ISCIII-Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER).

Objectives: This study aims to determine similarities and differences in clinical characteristics between the patients from two waves of severe acute respiratory syndrome coronavirus-2 infection at the time of hospital admission, as well as to identify risk biomarkers of coronavirus disease 2019 severity. Design: Retrospective observational study. Setting: A single tertiary-care center in Madrid. Patients: Coronavirus disease 2019 adult patients admitted to hospital from March 4, 2020, to March 25, 2020 (first infection wave), and during July 18, 2020, and August 20, 2020 (second infection wave). Interventions: Treatment with a hospital-approved drug cocktail during hospitalization. Measurements and Main Results: Demographic, clinical, and laboratory data were compared between the patients with moderate and critical/fatal illness across both infection waves. The median age of patients with critical/fatal coronavirus disease 2019 was 67.5 years (interquartile range, 56.75–78.25 yr; 64.5% male) in the first wave and 59.0 years (interquartile range, 48.25–80.50 yr; 70.8% male) in the second wave. Hypertension and dyslipidemia were major comorbidities in both waves. Body mass index over 25 and presence of bilateral pneumonia were common findings. Univariate logistic regression analyses revealed an association of a number of blood parameters with the subsequent illness progression and severity in both waves. However, some remarkable differences were detected between both waves that prevented an accurate extrapolation of prediction models from the first wave into the second wave. Interleukin-6 and d-dimer concentrations at the time of hospital admission were remarkably higher in patients who developed a critical/fatal condition only during the first wave (p < 0.001), although both parameters significantly increased with disease worsening in follow-up studies from both waves. Multivariate analyses from wave 1 rendered a predictive signature for critical/fatal illness upon hospital admission that comprised six blood biomarkers: neutrophil-to-lymphocyte ratio (≥ 5; odds ratio, 2.684 [95% CI, 1.143–6.308]), C-reactive protein (≥ 15.2 mg/dL; odds ratio, 2.412 [95% CI, 1.006–5.786]), lactate dehydrogenase (≥ 411.96 U/L; odds ratio, 2.875 [95% CI, 1.229–6.726]), interleukin-6 (≥ 78.8 pg/mL; odds ratio, 5.737 [95% CI, 2.432–13.535]), urea (≥ 40 mg/dL; odds ratio, 1.701 [95% CI, 0.737–3.928]), and d-dimer (≥ 713 ng/mL; odds ratio, 1.903 [95% CI, 0.832–4.356]). The predictive accuracy of the signature was 84% and the area under the receiver operating characteristic curve was 0.886. When the signature was validated with data from wave 2, the accuracy was 81% and the area under the receiver operating characteristic curve value was 0.874, albeit most biomarkers lost their independent significance. Follow-up studies reassured the importance of monitoring the biomarkers included in the signature, since dramatic increases in the levels of such biomarkers occurred in critical/fatal patients over disease progression. Conclusions: Most parameters analyzed behaved similarly in the two waves of coronavirus disease 2019. However, univariate logistic regression conducted in both waves revealed differences in some parameters associated with poor prognosis in wave 1 that were not found in wave 2, which may reflect a different disease stage of patients on arrival to hospital. The six-biomarker predictive signature reported here constitutes a helpful tool to classify patient’s prognosis on arrival to hospital.

We describe an unusual presentation of primary effusion lymphoma in CSF of a 45-year-old HIV-positive man, with no evidence of involvement of pleural, peritoneal or pericardial cavities. Cytologic examination and flow cytometric analysis suggested the diagnosis, eventually made in an excised deep cervical lymph node, in which the neoplastic cells involved selectively the sinuses. This case represents the fifth reported example of CSF involvement by this type of lymphoma, and supports the alleged connection between CSF and cervical lymph nodes via lymphatic vessels. Interestingly, review of an adenoidectomy specimen obtained 9 months before presentation for nonspecific complaints showed rare clusters of neoplastic cells involving surface epithelium and chorium, a finding that might represent a homing mechanism and implies an asymptomatic, occult phase of lymphoma development.

Resumen Introduccion y objetivo La meningoencefalitis criptococica (MC), aunque infrecuente, sigue siendo una importante causa de morbimortalidad en pacientes con sida. Material y metodos Revision de los casos de MC en un hospital universitario (1990-2014). El diagnostico se determino mediante el aislamiento de Cryptococcus neoformans en el LCR. Se analizo la morbimortalidad temprana ( Resultados Se analizaron 32 pacientes de los 2.269 diagnosticos de sida (1,41%): 10 entre 1990-1996 y 22 entre 1997-2014. El antigeno criptococico en el LCR fue positivo en todos los casos, con titulos > 1.024 en 19 pacientes (63%), presentando este grupo unos recuentos de CD4+ menores (40 ± 33 frente a 139 ± 78 cel/μl) y mayor afectacion diseminada que el resto. Tras el primer episodio de MC la tasa de recaidas fue del 34%. La mortalidad global fue del 28% (9/32), muy superior en el periodo pre-TARGA. Conclusiones La morbimortalidad de la MC viene determinada por padecer una inmunodeficiencia grave, la presencia de enfermedad diseminada, titulos elevados de antigeno en el LCR y el retraso en el inicio del TARGA.

Background Spain is the European country with the highest number of Trypanosoma cruzi infected patients. Due to the cardiac complications that these patients can develop, it is of paramount importance to evaluate the value of the different heart diagnostic tools. Method In this observational study, we describe the main characteristics and data from electrocardiogram, chest X-ray, echocardiogram and cardiac magnetic resonance imaging (MRI) of 141 patients with Chagas’ disease attended in a tertiary university hospital in Madrid from 2009 to 2018. Results A total of 50 patients (35.4%) had at least one abnormal cardiac test: 34.2% altered electrocardiogram (40/117), 24.5% altered echocardiogram (27/110) and 9.2% abnormal cardiac MRI (13/41). Of those 13 with a pathological MRI, 53.8% had normal results for any other test. The most frequent alterations observed were hypokinesia with decreased LVEF (left ventricular ejection fraction), dilatation of cavities and cardiac fibrosis. Two thirds of patients with abnormal cardiac test were asymptomatic. Altered echocardiogram was found in 43.8% of patients ≥50 years compared to 16.6% under 50 years (p = 0.003). Conclusions A transthoracic echocardiogram and a MRI of the heart added a 23.8% increment in diagnosing cardiac pathological findings.

Tinea nigra is an infrequent, superficial fungal infection, mainly caused by Hortaea werneckii, which is still underreported in Ethiopia. An asymptomatic 62-year-old male patient sought a rural hospital of Ethiopia, showing dark plaques on the palms of both hands. A superficial mycosis was suspected and a direct light microscopic mycological examination from skin scrapings revealed short brownish hyphae. To our knowledge, this is the first case of tinea nigra from the Ethiopian highlands. This may be due to the actual rarity of the condition or to underreporting.

[Background]: While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in human immunodeficiency virus (HIV)–infected subjects initiating antiretroviral therapy (ART) at advanced HIV disease remain unclear., [Methods]: This was a pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with, [Results]: Fifty-nine participants completed the follow-up with a mean CD4+ T-cell count of 221 ± 108 cells/μL and mean CD4/CD8 ratio of 0.26 ± 0.19. PMT25341 was well tolerated, without grade 3–4 adverse effects attributable to the intervention. While most of the assessed biomarkers improved during the follow-up in both arms, PMT25341-treated subjects did not experience any significant change, compared to placebo-treated subjects, in mean CD4+ T-cell count change (278 vs 250 cells/μL, P = .474) or CD4/CD8 ratio change (0.30 vs 0.32, P = .854). Similarly, we did not detect differences between treatment arms in secondary endpoints., [Conclusions]: In HIV-infected patients initiating ART at advanced disease, the clear immunological benefits of ART were not enhanced by this nutritional intervention targeting the gut-associated lymphoid tissue and microbiota., [Clinical Trials Registration]: NCT00870363., This work was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013–2016, projects PI13/00438, AC15/00022, and PI15/00345, and the Spanish AIDS Research Network RD16/0025/0001project), the Spanish Ministry of Science and Competitiveness (project SAF2015-65878-R), and co-financed by the European Development Regional Fund “A Way to Achieve Europe.” The present investigation was also funded by the Instituto de Salud Carlos III and the Fundación Asociación Española contra el Cáncer within the ERA (European Research Area)-NET aligning national/regional translational cancer research programmes and activities (TRANSCAN)-2 program (grant number AC17/00022). S. S.-V. was supported by a grant from the Spanish Ministry of Science and Competitiveness (Contratos Juan Rodés, ECC/1051/2013).

The magnitude of sexualized drug use (SDU), also known as chemsex, and its association with sexually transmitted infections (STI) has not been systematically explored in HIV-positive patients. This study aimed to calculate the prevalence of SDU and associated factors in a sample of HIV-positive men who have sex with men (MSM) in Spain. We calculated the frequency of SDU in a sample of HIV-positive MSM who responded to an anonymous online survey on sexual behavior and recreational drug use. We also analyzed differences between those who responded and those who did not (data taken from the physician's registry). The association between SDU, sexual risk behaviors, and STI was evaluated using a univariate and a multivariate analysis. Data were collected and managed using Research Electronic Data Capture (REDCap). The survey was completed by 742 HIV-positive MSM, of whom 60% had had unprotected anal intercourse (UAI), 62% had been diagnosed with a STI, and 216 (29.1%) reported recent SDU (slamsex in 16% of cases). In the multivariate analysis, patients who engaged in SDU were more likely to have had high-risk sexual behaviors and a diagnosis of STI than participants who did not engage in SDU. A diagnosis of hepatitis C was independently associated with slamsex (5.2 [95% confidence interval (CI), 2.06-13.13]; p 0.001), chemsex (2.51 [95% CI, 1.28-4.91]; p = 0.007), and UAI (1.82 [95% CI, 0.90-3.70]; p = 0.094). The magnitude of SDU or chemsex in our sample is relatively high. We found a clear association between SDU, high-risk sexual behaviors, and STI including hepatitis C.

Introduction T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection. Patients and methods 96 HIV patients, 49 of them followed in the absence of cART (cART-naive group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored. Results Parameters significantly associated with CD4 depletion in cART-naive group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035). Conclusions Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.

Background Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. Design Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. Methods We evaluated effectiveness (defined as maintenance of HIV-1-RNA

HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay. Inter-group and intra-group differences were tested using non-parametric tests. Compared with the TX patients, the EC patients had smaller HIV reservoir not only in Trm but also in pTfh and non-pTfh subsets of memory CD4+ T-cells. The largest differences were observed in pTfh cells (p = 0.025). The pTfh and non-pTfh cells harbored similar levels of HIV-DNA in the EC (p = 0.60) and TX patients (p = 0.17); however, the contribution to HIV-DNA levels in memory CD4+ T-cells varied among the pTfh and non-pTfh subsets in both groups of patients. The EC patients showed smaller HIV reservoir in memory CD4+ cells, especially in the pTfh subset, a population of cells with a pivotal role in the antiviral immune response, suggesting a potential link between low levels of infection in pTfh cells and the ability of the EC patients to spontaneously control HIV replication. This study has been funded by project CP14/00198 integrated in the State Plan for Scientific and Technical Research and Innovation and co-funded by ISCIII-Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). N Rallón is a Miguel Servet investigator from the Spanish Carlos III Institute of Health (ISCIII), grant CP14/00198, Madrid, Spain. M García is a predoctoral student co-funded by CP14/00198 project and the Intramural Research Scholarship from IIS-FJD. Sí

Ninety-five percent of precursor lesions -high-grade squamous intraepithelial lesions (HSIL) and anal intraepithelial neoplasms (AIN)- and their progression to squamous anal cancer (AC) are induced by high-risk HPV (HR-HPV) serotypes 16 and 18. Their incidence is higher particularly in HIV-infected male patients who have sex with other males (HIV-MSM) (144/100,000/patients/year).

Background There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. Patients and methods Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. Results HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. Conclusions We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.

Background Since 2003, outbreaks of lymphogranuloma venereum (LGV) with anorectal syndrome have been increasingly recognized in many Western countries. All of them have been classified as LGV serovar L2b, mainly occurring in human immunodeficiency virus (HIV)-infected men who have had sex with men (MSM). We describe a series of 26 diagnosed cases of LGV proctitis in downtown Madrid, Spain, in 2014, after implementing routine diagnostic procedures for this disease in symptomatic MSM. Methods We conducted an observational study of patients with symptomatic proctitis attending an outpatient infectious diseases clinic in Madrid, Spain during calendar year 2014. Clinical, epidemiological, laboratory, and therapeutic data were gathered and analyzed. Results Twenty-six patients were included in the analysis. All were MSM, and 24 of them were HIV-positive. All patients reported having acute proctitis symptoms including tenesmus (85%), pain (88%), constipation (62%), or anal discharge (96%). Proctoscopy showed mucopurulent exudate (25 patients [96%]), and rectal bleeding, with mucosal erythema and/or oedema in all cases. Rectal swabs were obtained from all patients, and LGV serovar L2 was confirmed in all of them. The cure rate was 100% after standard treatments with doxycycline 100 mg twice per day for 3 weeks. Simultaneous rectal infections with other sexually transmitted pathogens (gonorrhoea, herpes simplex virus, Mycoplasma genitalium) and systemic sexually transmitted diseases (STDs) (syphilis, acute HIV, and hepatitis C infections) were also documented in 12 patients (46%), but these co-infections did not appear to influence the clinical manifestations of LGV. Conclusions Anorectal LGV is a common cause of acute proctitis and proctocolitis among HIV-infected MSM who practice unprotected anal sex, and it is frequently associated with other rectal STDs. The implementation of routine screening and prompt diagnosis of these rectal infections should be mandatory in all clinical settings attended by HIV and STD patients.

Objectives To describe the effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen in naive HIV-1-infected patients, as there is a lack of data with this combination. Methods This was an observational, retrospective, multicentre study in eight Spanish hospitals. All antiretroviral-naive patients ≥18 years old and starting abacavir/lamivudine + rilpivirine were included. Effectiveness (ITT and on-treatment) and safety (adverse events and laboratory parameters) were assessed during follow-up. Values are expressed as n (%) or median (IQR). The Wilcoxon signed-rank test was used to compare baseline and 6 and 12 month values. Results Eighty-four patients were included [93% males, age = 36 (30-45) years]. Time since HIV diagnosis was 12 (4-35) months. Fifty-one per cent of patients had comorbidities. Baseline CD4+ was 425 (340-519) cells/mm3 and baseline HIV-RNA was 19 000 (9500-42 000) copies/mL. Median follow-up was 18 (9-22) months; 100% and 68% patients with at least 6 and 12 months, respectively. At 6 and 12 months effectiveness was 94% and 86% by ITT analysis and 96% and 97% by on-treatment analysis. At 12 months, there were significant increases in CD4+ (+262 cell/mm3) and HDL cholesterol (+4 mg/dL) and a significant decrease in the total cholesterol/HDL cholesterol ratio (-0.2). There were two (2.4%) virological failures (HIV-RNA 50-100 copies/mL); one patient later achieving virological suppression without changing the treatment. Six patients (7.1%) changed treatment due to reasons other than virological failure or side effects. One patient discontinued treatment due to gastrointestinal complaints attributed to abacavir/lamivudine. Conclusions Abacavir/lamivudine + rilpivirine was an effective and safe option in a selected group of HIV-1-infected treatment-naive patients.