Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. We evaluated the mortality, the risk of need for mechanical ventilation (MV), or death and the risk of developing a severe acute respiratory distress syndrome (ARDS) between high (HD) and standard doses (SD) among patients with a severe COVID-19. All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an ARDS. Patients were allocated to the HD (≥ 250 mg/day of methylprednisolone) of corticosteroids or the SD (≤ 1.5 mg/kg/day of methylprednisolone) at discretion of treating physician. Five hundred seventy-three patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54-73) years. In the HD group, a worse baseline respiratory situation was observed and male gender, older age, and comorbidities were significantly more common. After adjusting by baseline characteristics, HDs were associated with a higher mortality than SD (adjusted OR 2.46, 95% CI 1.59-3.81, p < 0.001) and with an increased risk of needing MV or death (adjusted OR 2.35, p = 0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients. Our real-world experience advises against exceeding 1-1.5 mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.

We describe the first 25 persons with HIV diagnosed with MPXV in our hospital in an ongoing outbreak in Spain. Proctitis was the predominant finding in 52%, and MPXV DNA was detected in rectal swabs from 90%. Proctitis and demonstration of MPXV in rectal swabs support the sexual transmission of MPXV.

Our objective is to assess the characteristics of respiratory syncytial virus (RSV) infection in adult patients and to establish differences with influenza viruses. Fiftyfour patients diagnosed with RSV and 198 with influenza were prospectively included. Compared with influenza, empirical antimicrobial therapy was more frequent in patients diagnosed with RSV, whereas antibiotic withdrawal at the time of diagnosis confirmation was lower (OR, 0.12; CI, 95% 0.01-0.90; P = 0.040). RSVpositive patients were more likely to need hospital readmission (OR, 3.00; CI, 95% 0.98-9.09; P = 0.053). The role of RSV infection in adults is often overlooked, leading to inappropriate use of antibiotics and a probable increase in nosocomial RSV transmission. K E Y W O R D Sinfluenza virus, respiratory infection, respiratory syncytial virus, seasonal incidence

BackgroundBecause 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.MethodsNested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.ResultsWe 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, 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), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-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).ConclusionsIn this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.

In the last decade, studies in PWH on ART have shed light on the significance of persistently high CD8 counts and low CD4/CD8 ratios. A low CD4/CD8 ratio translates increased immune activation and is associated with an increased risk of severe non-AIDS events. As a result, many clinicians now believe that the CD4/CD8 ratio can help in HIV monitoring, and many researchers now report it as an efficacy marker in interventional studies. However, the topic is more complex. Recent studies have not yielded unanimous conclusions on the ability of CD4/CD8 ratio to predict adverse outcomes, and only some clinical guidelines recommend monitoring it. Knowledge gaps remain on the best cut-off points, associated clinical events, effects of treatments, and how CD4/CD8 ratio could improve decision-making in the clinic. Here, we critically review the literature, identify knowledge gaps and discuss the role of the CD4/CD8 ratio as a marker for HIV monitoring.

BackgroundThe initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4/CD8 ratio recovery than INSTI-based 3DR.MethodsWe emulated a target trial using observational data from the Spanish HIV Research Network cohort (CoRIS). The outcomes of interest were the normalization of the CD4/CD8 ratio at 48 weeks using three different cutoffs: 0.5, 1.0, and 1.5. We matched each participant who started 2DR with up to four participants who received 3DR. Subsequently, we fitted generalized estimating equation (GEE) models and used the Kaplan–Meier method for survival curves.ResultsWe included 485, 805, and 924 participants for cutoffs of 0.5, 1.0, and 1.5, respectively. At 48 weeks, 45% of participants achieved a CD4/CD8 ratio &gt;0.5, 15% achieved a ratio &gt;1.0, and 6% achieved a ratio &gt;1.5. GEE models yielded a similar risk of reaching a CD4/CD8 ratio &gt;0.5 (OR 1.00, 95% CI 0.67 - 1.50), CD4/CD8 &gt;1.0 (OR 1.03, 95% CI 0.68 - 1.58), and CD4/CD8 &gt;1.5 (OR 0.86, 95% CI 0.48 - 1.54) between both treatment strategies. There were no differences between 2DR and 3DR in the incidence ratio of CD4/CD8 ratio normalization at 0.5, 1.0 and 1.5 cut-offs.ConclusionsIn this large cohort study in people with HIV, ART initiation with dolutegravir plus lamivudine vs. dolutegravir or bictegravir-based triple antiretroviral therapy showed no difference in the rates of CD4/CD8 normalization at 48 weeks.

Background Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF. Methods Multicenter prospective cohort study in the Spanish CoRIS cohort. We included virologically suppressed adults with HIV receiving TDF for more than 12 months who either switched to TAF or maintained TDF, with no changes in the core agent. Participants were matched by propensity score. We fitted generalized equation models to assess changes in weight, blood lipids, and hepatic steatosis index, and to compare the incidence of diabetes, hypertension, and lipid-lowering drug use after 144 weeks. Results 1,446 participants were matched in each group. Median age was 38 years, 85% were male, mean weight at baseline was 73 kilograms. Participants who switched to TAF had a mean weight increase of +0.5 kg at 144 weeks over those who maintained TDF, with no difference in the occurrence of overweight or obesity. Individuals who switched to TAF had a significant increase in total cholesterol (+7.9 mg/dL) and triglycerides (+11.2 mg/dL), with no differences in the total cholesterol-HDL ratio. However, no increased incidence of diabetes, hypertension, or lipid-lowering drug use was observed after the follow-up period. Conclusions Switching from TDF to TAF is associated with modest weight gain and increases in total cholesterol and triglycerides, without an impact on the incidence of obesity or metabolic-related clinical events, in this Spanish cohort with a majority white male population.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread rapidly worldwide. The role of immunosuppression among COVID-19 patients has not been elucidated and management may be challenging.OBJECTIVE: To assess differences in severe outcomes of hospitalized patients with COVID-19 according to immune system state.DESIGN: Retrospective single-center observational study with confirmed COVID-19 patients admitted to Hospital Universitario Ramón y Cajal from March 18, 2020 to April 04, 2020. The final date of follow-up was April 09, 2020.PARTICIPANTS: Confirmed COVID-19 patients.MAIN MEASURES: The primary endpoint was development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or non-invasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints.KEY RESULTS: Of 138 patients included, 29 (21%) were immunocompromised (IC), with 95 (68.8%) male patients and a median (IQR) age of 68 (54 – 78) years. Among the baseline characteristics, no relevant or significant differences were observed between IC and non-immunocompromised (non-IC) patients. A significantly lower proportion of IC patients (24.1% [95% CI, 11.4 – 44.0%]) compared to non-IC patients (49.5% [95% CI, 40.1 – 59.0%]) developed moderate-severe ARDS, in both unadjusted (OR 0.32 [95% CI, 0.13 – 0.82], p=0.018) and adjusted (aOR 0.16 [95% CI, 0.05 – 0.52], p=0.003) analyses. A positive non-significant trend toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected in IC. A trend toward a shorter- hospitalization in IC was observed.CONCLUSIONS: In our cohort of COVID-19 patients, immunosuppression was associated with a lower risk of moderate-severe ARDS. This suggests a potential protective effect from a hypothesized host hyper-inflammatory response and warrants reconsideration of drug discontinuation in IC patients.