Real-life data of immune recovery using bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed people living with HIV. Results at 48-96†weeks of RETROBIC Study.

BACKGROUND: Switching strategy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has become a gold standard for people living with HIV (PLWH), achieving high efficacy and safety rates. However, data regarding immune status in long-term real-life cohorts of pretreated patients are needed. METHODS: We performed a multicentre, non-controlled, retrospective study in virologically suppressed PLWH switching to B/F/TAF. We evaluated CD4+, CD8+ and CD4+/CD8+ ratio, efficacy and safety at weeks 48 and 96. RESULTS: The study comprised 1966 PLWH from 12 hospitals in Spain, of whom 80% were men, and the median age was 51.0 [42.0-57.0] years. The median time of HIV infection was 18.0 [10.0-27.0] years. No significant changes in CD4+, CD8+ T cells, or CD4+/CD8+ were observed after 96 weeks. Nevertheless, in women at weeks 48 and 96, we found a significant increase of CD4+ T cells and a significant decrease in CD8+ T cells. In patients ≥60 years at week 96, CD4 T cells significantly increased and CD8+ T cells significantly decreased at week 48. The on-treatment analysis revealed HIV-RNA <50 copies/mL in 95.6% (1700/1779) and 96.7% (1312/1356) of patients at weeks 48 and 96, respectively. The rates increased to 99.2% (1765/1779) and 99.7% (1352/1356) when considering HIV-RNA <200 copies/mL. No resistance mutations were detected in virologic failures. B/F/TAF discontinuations accounted for 10.2% (200). Simplification was the most common reason for discontinuation in 3.8% (74) of patients. CONCLUSION: In long-term virologically controlled PLWH, B/F/TAF achieved high efficacy rates and slightly improved immune status in women and individuals aged 60 and over after 48 and 96 of switching.

Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses.

BACKGROUND: Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. METHODS: We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. RESULTS: In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024). CONCLUSION: For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.

Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge.

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4-), and, to a lower extent, in B-cells from healthy controls. Notably, IDE's surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE's surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4- T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4- T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19.

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Corticosteroid Pulses for Hospitalized Patients with COVID-19: Effects on Mortality.

OBJECTIVES: To assess the influence of corticosteroid pulses on 60-day mortality in hospitalized patients with severe COVID-19. METHODS: We designed a multicenter retrospective cohort study in three teaching hospitals of Castilla y León, Spain (865,096 people). We selected patients with confirmed COVID-19 and lung involvement with a pO2/FiO2<300, excluding those exposed to immunosuppressors before or during hospitalization, patients terminally ill at admission, or those who died in the first 24 hours. We performed a propensity score matching (PSM) adjusting covariates that modify the probability of being treated. Then, we used a Cox regression model in the PSM group to consider factors affecting mortality. RESULTS: From 2933 patients, 257 fulfilled the inclusion and exclusion criteria. 124 patients were on corticosteroid pulses (250 mg of methylprednisolone for three days), and 133 were not. 30.3% (37/122) of patients died in the corticosteroid pulse group and 42.9% (57/133) in the nonexposed cohort. These differences (12.6%, 95% CI [8·54-16.65]) were statically significant (log-rank 4.72, p = 0, 03). We performed PSM using the exact method. Mortality differences remained in the PSM group (log-rank 5.31, p = 0.021) and were still significant after a Cox regression model (HR for corticosteroid pulses 0.561; p = 0.039). CONCLUSIONS: This study provides evidence about treatment with corticosteroid pulses in severe COVID-19 that might significantly reduce mortality. Strict inclusion and exclusion criteria with that selection process set a reliable frame to compare mortality in both the exposed and nonexposed groups.

Clinical predictors of candidemia in medical non-neutropenic, non-ICU patients. The CaMed score.

INTRODUCTION: Candida species are the leading cause of invasive fungal infections in hospitalised patients and are the fourth most common isolates recovered from patients with bloodstream infection. Few data exist on risk factors for candidemia in non-ICU patients. We performed a population-based case-control study to evaluate the main predictors for candidemia in non-ICU patients. METHODS AND FINDINGS: We included all non-neutropenic, non-critically ill and non-surgical adult patients with candidemia between January 2010 and June 2014. Patients with positive, non-candidal blood culture obtained at the same day (±2 days) were selected as controls. Cases and controls were matched according to hospital ward and clinical characteristics. Risk factors for candidemia were identified through a logistic regression. We included 56 candidemic and 512 bacteriemic non-candidemic patients. Most of candidemic patients (52) had received antibiotics prior to candidemia. Among them, the 30-day mortality rate was 34% (19/56). Multivariate analysis identified male sex, prior use of steroids, prior use of antibiotics, total parenteral nutrition and urinary catheterisation as independent predictors of candidemia. To develop the CaMed score, we rounded up weights of different risk factors as follows; total parenteral nutrition (+2), prior antibiotic therapy (+5), each of the other risk factors (+1). A score ≥ 7 identified patients at high risk of candidemia (P < 0.001; RR 29.805; CI 95% 10.652-83.397; sensitivity 79.2, specificity 82.6%, Youden index 0,62). CONCLUSIONS: Our set of easy independent predictors of candidemia in non-neutropenic, non-ICU, non-surgical patients provide a rationale for early initiation of antifungals and could reduce candidemia-related mortality.

Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain.

This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n = 101) of the XDR isolates, distantly followed by ST244 (n = 16), ST253 (n = 12), ST235 (n = 8), and ST111 (n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n = 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the ß-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in ß-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.

Executive summary of the consensus document on post-exposure prophylaxis against HIV, HBV and HCV in adults and children.

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.

[Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus]. / Documento de consenso sobre alteraciones metabólicas y riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana.

OBJECTIVE: This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. METHODS: This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. RESULTS: A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. CONCLUSIONS: These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included.

Executive summary of the consensus document on metabolic disorders and cardiovascular risk in patients with HIV infection.

The importance of the metabolic disorders and their impact on patients with HIV infection requires an individualized study and continuous updating. HIV patients have the same cardiovascular risk factors as the general population. The HIV infection per se increases the cardiovascular risk, and metabolic disorders caused by some antiretroviral drugs are added risk factors. For this reason, the choice of drugs with a good metabolic profile is essential. The most common metabolic disorders of HIV infected-patients (insulin resistance, diabetes, hyperlipidemia or osteopenia), as well as other factors of cardiovascular risk, such as hypertension, should also be dealt with according to guidelines similar to the general population, as well as insisting on steps to healthier lifestyles. The aim of this document is to provide a query tool for all professionals who treat HIV-patients and who may present or display any metabolic disorders listed in this document.

Predict the Effects of Dolutegravir (DTG) Plus Lamivudine (3TC) on Immunological Responses in People Living with HIV (PLWHIV).

BACKGROUND: Immune recovery in people living with HIV (PLWHIV) is a residual aspect of antiretroviral treatment (ART) in most patients, but in a non-negligible proportion of them, the CD4+ lymphocytes count, or CD4/CD8 ratio remains suboptimal. METHODS: We performed a model of the immune response after 24 weeks of switching to a 2DR with DTG plus 3TC in a retrospective multicenter cohort of undetectable and experienced patients using significant predictor variables associated with the parameters or situations defined as success and failure. Clinical variables studied were CD4+ and CD8+ lymphocyte count, percentage of CD4, and CD4/CD8 ratio. These parameters were assessed at baseline and 24 weeks after the switch. Based on the evolution of each variable, four categories of immune response and four categories of non-immune response were defined. Immune response was defined as CD4+ count > 500 cells/mm3, %CD4 > 30%, CD8+ count < 1000 cells/mm3 and CD4/CD8 ratio ≥ 0.9. Non-response is just the opposite. RESULTS: In our different models of immunological response, the presence of stage of AIDS (p = 0.035, p = 0.065) and current age over 50 years (p = 0.045) are postulated as statistically significative limiting factors in achieving an improvement in CD4, %CD4, CD8, and CD4/CD8 ratio. Late HIV diagnosis (p = 0.156), without statistical significance, enhanced late the previous variables. In contrast, conditions where patients start with CD4 > 500 cells/mm3 (p = 0.054); CD4 > 30% (p = 0.054, p = 0.084); CD8 < 1000 cells/mm3 (p = 0.018), and CD4/CD8 ≥ 0.9 (p = 0.013, p = 0.09) are detected as stimulating or conducive to DTG plus 3TC treatment success. CONCLUSION: These models represent a proof of concept that could become a valuable tool for clinicians to predict the effects of DTG plus 3TC on immunological responses prior to the switch in undetectable pre-treated PLWHIV with immune dysfunction. The main predictors for immunological failure were late HIV diagnosis, stage of AIDS, and current age over 50 years. In contrast, starting with a normalized immune status was detected as stimulating or conducive to DTG plus 3TC treatment success.

Dolutegravir Plus 3TC in Virologically Suppressed PLWHIV: Immunological Outcomes in a Multicenter Retrospective Cohort in Spain during the COVID-19 Pandemic.

Dolutegravir (DTG) based dual therapies for treating PLWHIV are a standard of care nowadays. Switching to DTG and lamivudine (3TC) safety and efficacy were proven in TANGO randomized clinical trial. This multicenter retrospective study included 1032 HIV virologically suppressed patients switching to DTG+3TC from 13 Spanish hospitals. DTG+3TC provided high rates of undetectable viral load over 96%, corresponding to 96.6% (889/921) at 24 weeks, 97.5% (743/763) at 48 weeks, and 98.3% (417/425) at 96 weeks. No significant differences are evident when comparing the total population according to sex, presence of comorbidity, or presence of AIDS. The analysis for paired data showed an increase in CD4+ cell count. A statistically significant increase in CD4+ lymphocyte count was found in those without comorbidities in the three-time series analyzed [average increase at 24 weeks: 48.7 (SD: 215.3) vs. 25.8 (SD: 215.5), p-value = 0.050; a mean increase at 48 weeks: 75.1 (SD: 232.9) vs. 42.3 (SD: 255.6), p-value = 0.003; a mean increase at 96 weeks: 120.1 (SD: 205.0) vs. 63.8 (SD:275.3), p-value = 0.003]. In conclusion, our cohort demonstrates that DTG+3TC is an effective treatment strategy for virologically-suppressed PLWHIV independent of age, sex, and HIV stage, as well as a safe and durable strategy.

Use of Antivirals in SARS-CoV-2 Infection. Critical Review of the Role of Remdesivir.

The aim of this report is to review the literature and shed light on the uncertainties surrounding the use of antiviral agents in general and remdesivir in COVID-19 patients. This review evaluated a battery of antiviral compounds and their effectiveness in the treatment of COVID-19 since the beginning of the pandemic. Remdesivir is the only antiviral approved by the EMA and FDA for the treatment of SARS-CoV-2 infection. This work extensively reviews remdesivir data generated from clinical trials and observational studies, paying attention to the most recent data, and focusing on outcomes to give readers a more comprehensive understanding of the results. This review also discusses the recommendations issued by official bodies during the pandemic in the light of the current knowledge. The use of remdesivir in the treatment of SARS-CoV-2 infection is justified because a virus is the causative agent that triggers the inflammatory responses and its consequences. More trials are needed to improve the management of this disease.

Tenofovir disoproxil fumarate/emtricitabine and severity of coronavirus disease 2019 in people with HIV infection.

BACKGROUND: Effective, safe, and affordable antivirals are needed for coronavirus disease 2019 (COVID-19). Several lines of research suggest that tenofovir may be effective against COVID-19, but no large-scale human studies with appropriate adjustment for comorbidities have been conducted. METHODS: We studied HIV-positive individuals on antiretroviral therapy (ART) in 2020 at 69 HIV clinics in Spain. We collected data on sociodemographics, ART, CD4+ cell count, HIV-RNA viral-load, comorbidities and the following outcomes: laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, intensive care unit (ICU) admission and death. We compared the 48-week risks for individuals receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and other regimes. All estimates were adjusted for clinical and sociodemographic characteristics via inverse probability weighting. RESULTS: Of 51 558 eligible individuals, 39.6% were on TAF/FTC, 11.9% on TDF/FTC, 26.6% on ABC/3TC, 21.8% on other regimes. There were 2402 documented SARS-CoV-2 infections (425 hospitalizations, 45 ICU admissions, 37 deaths). Compared with TAF/FTC, the estimated risk ratios (RR) (95% confidence interval) of hospitalization were 0.66 (0.43, 0.91) for TDF/FTC and 1.29 (1.02, 1.58) for ABC/3TC, the RRs of ICU admission were 0.28 (0.11, 0.90) for TDF/FTC and 1.39 (0.70, 2.80) for ABC/3TC, and the RRs of death were 0.37 (0.23, 1.90) for TDF/FTC and 2.02 (0.88-6.12) for ABC/3TC. The corresponding RRs of hospitalization for TDF/FTC were 0.49 (0.24, 0.81) in individuals ≥50 years and 1.15 (0.59, 1.93) in younger individuals. DISCUSSION: Compared with other antiretrovirals, TDF/FTC lowers COVID-19 severity among HIV-positive individuals with virological control. This protective effect may be restricted to individuals aged 50 years and older.

Dolutegravir plus rilpivirine: benefits beyond viral suppression: DORIPEX retrospective study.

ABSTRACT: Switching dual therapy with dolutegravir (DTG) plus rilpivirine (RPV) was assessed in the SWORD-1 and SWORD-2 studies. Real-life data regarding the immunological impact of this approach on CD4+ and CD8+ T lymphocyte counts and the CD4/CD8 ratio are scarce. We evaluated this strategy on the basis of clinical practice data.A multicentric retrospective cohort study.Treatment-experienced virologically suppressed HIV-1-infected patients who were switched to DTG plus RPV were included. Using different models for paired data, we evaluated the efficacy and immune status in terms of CD4+ and CD8+ T-cell counts and CD4/CD8 ratio at 24 and 48 weeks of treatment.The study population comprised of 524 patients from 34 centers in Spain. Men accounted for 76.9% of patients, with a median age of 53 years. Patients receiving DTG plus RPV reached weeks 24 and 48 in 99.4% and 83.8% of cases, respectively, with only three (0.57%) virological failures. We found a significant decrease in CD8+ T-cell count (log OR -40) at week 24 and an increase in CD4+ T-cell count at week 48 (log OR +22.8). In acquired immunodeficiency syndrome-diagnosed patients, we found a significant increase in the CD4+ T-cell count at week 48 (log OR = 41.7, P = .0038), but no significant changes in the CD8+ T-cell count (log OR = -23.4, P = .54). No differences were found in the CD4/CD8 ratio between the acquired immunodeficiency syndrome subgroup and sex or age.In patients with controlled treatment, dual therapy with DTG plus RPV slightly improved the immune status during the first 48 weeks after switching, not only in terms of CD4+ T-cell count but also in terms of CD8+ T-cell count, with persistently high rates of viral control.

Chronic use of renin-angiotensin-aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis.

Background: Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin-angiotensin-aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. Methods: We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. Results: Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (-0.151 [95% CI -0.218, -0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (-0.167 [95% CI -0.220, -0.114]) and during hospitalization (0.090 [-0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224-0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42-0.8]) among hypertensive COVID-19. Conclusion: Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.

Introducción: La hipertensión es una condición prevalente entre los pacientes infectados por el SARS-CoV-2. Es controvertido si los inhibidores del sistema renina-angiotensina-aldosterona (SRAA) son beneficiosos o perjudiciales. Métodos: Hemos desarrollado un estudio comparativo nacional retrospectivo y no experimental en 2 hospitales terciarios para evaluar el impacto del uso crónico de inhibidores del SRAA en pacientes hipertensos con COVID-19. Se realizó un metaanálisis para reforzar los hallazgos. Resultados: De 849 pacientes, 422 (49,7%) eran hipertensos y 310 (73,5%) tomaban inhibidores del SRAA al inicio del estudio. Los pacientes hipertensos eran mayores, tenían más comorbilidades y una mayor incidencia de insuficiencia respiratoria (−0,151; IC 95%: [−0,218; −0,084]). La mortalidad global en los pacientes hipertensos fue del 28,4%, pero fue menor entre los que tenían prescritos inhibidores del SRAA antes (−0,167; IC 95%: [−0,220; −0,114]) y durante la hospitalización (0,090; [−0,008; 0,188]). Se observaron hallazgos similares tras 2 emparejamientos de puntuación de propensión que evaluaron el beneficio de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina entre los pacientes hipertensos. El análisis de regresión logística multivariante de los pacientes hipertensos reveló que la edad, la diabetes mellitus, la proteína C reactiva y la insuficiencia renal se asociaban de forma independiente con la mortalidad por todas las causas. Por el contrario, los inhibidores de la enzima convertidora de angiotensina disminuyeron el riesgo de muerte (OR 0,444; IC 95%: 0,224-0,881). El metaanálisis indicó un beneficio protector de los inhibidores del SRAA (OR 0,6; IC 95%: 0,42-0,8) entre los hipertensos con COVID-19. Conclusión: Nuestros datos indican que los inhibidores del SRAA pueden desempeñar un papel protector en los pacientes hipertensos con COVID-19. Este hallazgo fue apoyado por un metaanálisis de la evidencia actual. Su mantenimiento durante la estancia hospitalaria puede no afectar negativamente a los resultados de la COVID-19.

Chronic use of renin-angiotensin-aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis.

BACKGROUND: Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin-angiotensin-aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. METHODS: We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. RESULTS: Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (-0.151 [95% CI -0.218, -0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (-0.167 [95% CI -0.220, -0.114]) and during hospitalization (0.090 [-0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224-0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42-0.8]) among hypertensive COVID-19. CONCLUSION: Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.