The presence of resistance-associated mutations in reverse transcriptase gene is associated with cerebrospinal fluid HIV-1 escape: A multicentric retrospective analysis.

Higher risk of cerebrospinal fluid escape (CVE) has been associated with the use of specific antiretroviral (ARV) classes, such as protease inhibitors. We assessed whether archived resistance-associated mutations (RAMs) can mediate this relationship by identifying patients treated with incompletely active antiretroviral regimens. A retrospective multicentric study on 282 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modeling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modeling the risk. Median age, plasma VL, and CD4 count were 49 years, <50 copies/mL, and 310 cells/µL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs. 32.1%, p = 0.005) and CSF RAMs in RT (n = 63, 57.1% vs. 28.6%, p = 0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p < 0.001) and in models restricted to plasma viral load ≤50 copies/mL (n = 202; aOR 4.3, p = 0.003). CVE risk decreased by 40% per each point increase in HGRT-adjusted CPE score in multivariable models (p < 0.001). Rather than the type of ARV classes or of ART regimens, functional mono or dual regimens caused by the presence of RAMs affecting ART components may explain the majority of cases of CVE.

Analysis of serum microRNAs and rs2910164 GC single-nucleotide polymorphism of miRNA-146a in COVID-19 patients.

Alteration of micro-RNAs (miRNAs) expression, including miRNA-122a, -146a and -205 family members, can have profound effects on inflammatory and IFN pathways (miRNA-146a), known as hallmarks of COVID-19. SARS-CoV-2-infected patients were recruited at Policlinico Umberto I Hospital of Sapienza University of Rome (Italy). MiRNA-122a, -146a, -205 and IFI27 (Interferon Alpha Inducible Protein 27) levels were screened in SARS-CoV-2 patients (n = 14) and healthy controls (n = 10) by real-time RT-PCR assays. Then, miRNA-146a rs2910164 GC single-nucleotide polymorphism (SNP) was genotyped in a larger group of COVID-19 patients (n = 129), and its relationship with severe disease [Intensive Care Unit (ICU) support or survival/death] was assessed. SARS-CoV-2-positive patients had increased PCR, D-Dimer and Fibrinogen levels compared to healthy controls (p < .05 for all measurements). MiRNA-122a and -146a serum levels were upregulated in COVID-19 patients (miRNA-122a: p = .002; miRNA-146a: p < .001). Decreased IFI27 levels were observed in COVID-19 patients with higher miRNA-146a levels (p = .047). Moreover, miRNA-146a rs2910164 C/G genotypes distributions were similar in COVID-19 patients and in validated European healthy subjects (n = 37,214). MiRNA-146a SNP was not associated with severe COVID-19 outcome (ICU or death). MiRNA-122a and -146a levels were elevated in SARS-CoV-2 infected patients, with miRNA-146a upregulation possibly contributing to IFN pathways dysregulation (e.g., reduced IFI27 levels) observed in severe COVID-19, although there is no evidence for the involvement of rs2910164 SNP.

Efficacy and durability of two- vs. three-drug integrase inhibitor-based regimens in virologically suppressed HIV-infected patients: Data from real-life ODOACRE cohort.

OBJECTIVES: The aim of the present study was to compare the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug (3DR) integrase inhibitor (InSTI)-based regimens in a real-life setting. METHODS: Within the ODOACRE cohort, we selected adult patients with HIV RNA < 50 copies/mL switching to an InSTI-based 2DR or 3DR. Survival analyses were performed to estimate the probability of virological failure (VF, defined as one HIV RNA > 1000 copies/mL or two consecutive HIV RNA > 50 copies/mL) and treatment discontinuation (TD, defined as any modification, intensification or interruption of the regimen), and to evaluate their predictors. RESULTS: Overall, 1666 patients were included, of whom 1334 (80%) were treated with a 3DR (19.9%, 25.0% and 55.1% elvitegravir-, raltegravir- and dolutegravir-based, respectively) and 332 (20%) with a 2DR (79.2% dolutegravir + lamivudine and 20.8% dolutegravir + rilpivirine). Over a median (interquartile range) follow-up of 100 (52-150) weeks, 52 (3.1%) patients experienced VF with an incidence of 1.5/100 person-year of follow-up (PYFU). The estimated 96-week probability of VF was similar for the 2DR and 3DR groups (2.3% vs. 2.8%, P = 0.53), but it was higher for elvitegravir (4.9%) and raltegravir (5.0%) than for dolutegravir (1.5%) (P = 0.04). Four hundred (24%) patients discontinued their InSTI-based regimen, with an incidence of 11.3/100 PYFU. At 96 weeks, 3DRs showed a higher probability of TD for any reason (20.6% vs. 11.2%, P < 0.001) and TD for toxicity (9.0% vs. 6.6%, P = 0.02) when compared with 2DRs. A higher risk of TD for central nervous system toxicity was observed for dolutegravir than for elvitegravir and raltegravir (4.0% vs. 2.5% vs. 0.6%, P = 0.005). CONCLUSIONS: In virologically suppressed HIV-infected patients, 2DRs showed an efficacy similar to 3DRs but with better tolerability.

qSOFA as a new community-acquired pneumonia severity score in the emergency setting.

BACKGROUND: Quick Sequential Organ Failure Assessment (qSOFA) score is a bedside prognostic tool for patients with suspected infection outside the intensive care unit (ICU), which is particularly useful when laboratory analyses are not readily available. However, its performance in potentially septic patients with community-acquired pneumonia (CAP) needs to be examined further, especially in relation to early outcomes affecting acute management. OBJECTIVE: First, to compare the performance of qSOFA and CURB-65 in the prediction of mortality in the emergency department in patients presenting with CAP. Second, to study patients who required critical care support (CCS) and ICU admission. METHODS: Between January and December 2017, a 1-year retrospective observational study was carried out of adult (≥18 years old) patients presenting to the emergency department (ED) of our hospital (Rome, Italy) with CAP. The accuracy of qSOFA, qSOFA-65 and CURB-65 was compared in predicting mortality in the ED, CCS requirement and ICU admission. The concordance among scores ≥2 was then assessed for 30-day estimated mortality prediction. RESULTS: 505 patients with CAP were enrolled. Median age was 71.0 years and mortality rate in the ED was 4.7%. The areas under the curve (AUCs) of qSOFA-65, CURB-65 and qSOFA in predicting mortality rate in the ED were 0.949 (95% CI 0.873 to 0.976), 0.923 (0.867 to 0.980) and 0.909 (0.847 to 0.971), respectively. The likelihood ratio of a patient having a qSOFA score ≥2 points was higher than for qSOFA-65 or CURB-65 (11 vs 7 vs 6.7). The AUCs of qSOFA, qSOFA-65 and CURB-65 in predicting CCS requirement were 0.862 (95% CI 0.802 to 0.923), 0.824 (0.758 to 0.890) and 0.821 (0.754 to 0.888), respectively. The AUCs of qSOFA-65, qSOFA and CURB-65 in predicting ICU admission were 0.593 (95% CI 0.511 to 0.676), 0.585 (0.503 to 0.667) and 0.570 (0.488 to 0.653), respectively. The concordance between qSOFA-65 and CURB-65 in 30-day estimated mortality prediction was 93%. CONCLUSION: qSOFA is a valuable score for predicting mortality in the ED and for the prompt identification of patients with CAP requiring CCS. qSOFA-65 may further improve the performance of this useful score, showing also good concordance with CURB-65 in 30-day estimated mortality prediction.

Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study.

OBJECTIVES: Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals. METHODS: The cohort included 661 adults with bloodstream infections (BSIs; n = 447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible. RESULTS: Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤8 mg/L. CONCLUSIONS: KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.

Impact of pre-existent drug resistance on virological efficacy of single-tablet regimens in people living with HIV.

Despite the wide use of single-tablet regimens (STRs), few real-life data are available regarding the impact of pre-existent drug resistance on virological failure (VF). We aimed to fill this gap by analysing a large cohort of individuals selected from the ARCA database. The impact on VF of pre-existent resistance-associated mutations (RAMs) and cumulative genotypic susceptibility score (cGSS) before STR start was evaluated through survival analysis. Potential emergence of resistance at VF was also evaluated. Overall, 3916 individuals were included, comprising 678 treatment-naïve (G1), 2309 treatment-experienced aviraemic (G2) and 929 viraemic (G3), of whom 65.2% were treated with a STR based on efavirenz (35.2%) or rilpivirine (30.0%). At 2 years after starting a STR, the overall probability of VF was 5.9% in G1, 8.7% in G2 and 20.8% in G3. No impact of pre-existent resistance on VF was found in G1. The probability of VF was higher in patients with cGSS < 3 (reduced susceptibility to at least one drug) than in those with cGSS = 3 (full susceptibility to STR drugs) both in G2 and G3. A higher probability of VF was also found in the presence of pre-existent M184V (alone or in combination with pre-existent thymidine analogue mutations). Among patients who failed STR, a significant emergence of RAMs was found only in those exposed to EFV/FTC/TDF in G3 (specifically K103N and M184V). Our results confirm a high efficacy of STRs in clinical settings. Pre-existent resistance appears to influence virological efficacy of STRs in treatment-experienced individuals (both aviraemic and viraemic).

Oxygen Sparing Effect of Bacteriotherapy in COVID-19.

BACKGROUND: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. METHODS: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. RESULTS: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. CONCLUSIONS: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients' survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.

SARS-CoV-2 Among Migrants Recently Arrived in Europe From Low- and Middle-Income Countries: Containment Strategies and Special Features of Management in Reception Centers.

Despite the "migrants and COVID-19" topic has been neglected since felt marginal concerning other aspects of the SARS-CoV-2 pandemic, it represents a relevant public health issue in the European countries. This report describes COVID-19 containment strategies adopted in a large Italian reception center hosting recently arrived asylum-seeker migrants. Risk assessment and prevention measures adopted were described. Geo-spatial epidemiological analysis of the outbreak was reported. Significant gaps in the knowledge of self-protection measures from contagious diseases and in the perception of the pandemic risk were observed in migrants; health promotion activities, targeted to remove cultural barriers and improve behaviors appropriate to individual protection, were able to fulfill this gap. In low-resource settings, especially in closed communities, the implementation of social distancing strategies, the systematic use of individual protection devices, and active syndromic surveillance are essential tools to limit the risk of outbreaks. In the event of an outbreak, it is relevant to rapidly activate containment procedures based on systematic screening, isolation, and quarantine, taking into consideration the limits of tracing contacts within a closed community. Not being able to trace certain contacts, the geo-spatial epidemiological analysis of cases distribution could be key in the management of the outbreak. Interestingly, positive cases identified in our facility were all clinically pauci-symptomatic or asymptomatic. Dedicated strategies are needed to minimize the chance of SARS-CoV-2 transmission in a limited space such as reception centers and a vulnerable population such as migrants.

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients.

Long COVID refers to patients with symptoms as fatigue, "brain fog," pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB-). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB- one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.

Alzheimer Dementia in People Living With HIV.

OBJECTIVE: Given the aging of people living with HIV (PLWH) and the high prevalence of HIV-associated neurocognitive disorders, we aimed at describing the clinical, instrumental, and CSF features of PLWH diagnosed with Alzheimer dementia (AD). METHODS: The databases of 3 large Italian outpatient clinics taking care of more than 9,000 PLWH were searched for the diagnosis of AD. After obtaining patients' or their next of kin's consent for publication, anonymous data were collected in an excel spreadsheet and described. Routinely collected CSF biomarkers and radiologic imaging results were recorded whether available. RESULTS: Four patients were included in this case series who were diagnosed with AD aged between 60 and 74 years. All participants were on highly active antiretroviral therapy and showed nondetectable serum HIV RNA. Memory impairment was the most prominent cognitive feature. The diagnosis was obtained considering the exclusion of other potential causes, MRI and fluorodeoxyglucose-PET features, and, in (in 2/4), CSF AD biomarkers levels. In 1 patient, longitudinal CSF tau/p-tau increased, and beta-amyloid1-42 decreased over time despite antiretroviral therapy containing nucleotide reverse transcriptase inhibitors. CONCLUSIONS: In older PLWH cognitive symptoms may represent the onset of AD: a multidisciplinary team may be needed for reaching a likely in vivo diagnosis.

Clinical Characteristics and Outcome of Patients with Suspected COVID-19 in Emergency Department (RESILIENCY Study II).

OBJECTIVES: COVID-19 may show no peculiar signs and symptoms that may differentiate it from other infective or non-infective etiologies; thus, early recognition and prompt management are crucial to improve survival. The aim of this study was to describe clinical, laboratory, and radiological characteristics and outcomes of hospitalized COVID-19 patients compared to those with other infective or non-infective etiologies. METHODS: We performed a prospective study from March 2020 to February 2021. All patients hospitalized for suspected or confirmed COVID-19 were prospectively recruited. All patients were evaluated according to a predefined protocol for diagnosis of suspected SARS-CoV-2 infection. The primary endpoint was evaluation of clinical, laboratory, and radiological characteristics associated or not with COVID-19 etiology at time of hospitalization in an emergency department. RESULTS: A total of 1036 patients were included in the study: 717 (69%) patients with confirmed COVID-19 and 319 (31%) without COVID-19, hospitalized for other causes. The main causes of hospitalization among non-COVID-19 patients were acute heart failure (44%) and bacterial pneumonia (45.8%). Overall, 30-day mortality was 9% among the COVID-19 group and 35% in the non-COVID-19 group. Multivariate analysis showed variables (fever > 3 days, dry cough, acute dyspnea, lymphocytes < 1000 × 103/µL, and ferritin > 250 ng/mL) independently associated with COVID-19 etiology. A decision tree was elaborated to early detect COVID-19 patients in the emergency department. Finally, Kaplan-Meier curves on 30-day survival in COVID-19 patients during the first wave (March-May 2020, n = 289 patients) and the second wave (October-February 2021, n = 428 patients) showed differences between the two study periods (p = 0.021). CONCLUSIONS: Patients with confirmed diagnosis of COVID-19 may show peculiar characteristics at time of hospitalization that could help physicians to distinguish from other infective or non-infective etiologies. Finally, a different 30-day mortality rate was observed during different periods of the pandemic.

Dolutegravir-Based Regimen for Maintenance of Viral Suppression in People Living with HIV: 48-Week Results in Real-Life Setting.

To evaluate the efficacy, safety, and tolerability of switching to a dolutegravir (DTG)-based regimen in a cohort of virological suppressed HIV-infected patients who have previously been treated with different antiretroviral combination. The dynamics of total HIV-DNA and levels of high-sensitivity c-reactive protein, interleukin-6, soluble-CD14, and D-Dimer were also analyzed. Ninety-six individuals who switched to a DTG-containing regimen were followed up for 48 weeks. HIV RNA, CD4+ T cell count, weight, and levels of laboratory parameters were recorded at baseline, after 24 and 48 weeks of treatment for all study participants. In a subgroup of patients, HIV DNA and inflammation/coagulation marker levels were also analyzed until week 24. Ninety-three out of 96 patients maintained virological suppression, including patients who switched to dual-therapy from triple-drug combination. Eighteen out of 96 patients had residual viremia at baseline, of which 13 reached the maximal viral suppression at W48. Serum creatinine levels showed a significant increase at weeks 24 and 48. A progressive reduction of total cholesterol was observed from week 24 and up to week 48. No variation in body mass index was detected. HIV DNA, inflammation, and coagulation marker levels did not significantly change during follow-up. Switching to a DTG-based regimen may be a key option for achieving and maintaining maximal virological suppression, even in patients showing residual viremia at baseline. Furthermore, the improvement in blood lipid profile and the overall tolerability observed in this study strongly support the use of these regimens in the aging HIV population.

Malaria in an asylum seeker paediatric liver transplant recipient: diagnostic challenges for migrant population.

Transplanted patients are particularly exposed to a major risk of infectious diseases due to prolonged immunosuppressive treatment. Over the last decade, the growing migration flows and the transplant tourism have led to increasing infections caused by geographically restricted organisms. Malaria is an unusual event in organ transplant recipients than can be acquired primarily or reactivation following immunosuppression, by transfusion of blood products or through the transplanted organ. We report a rare case of Plasmodium falciparum infection in a liver transplanted two years-old African boy who presented to one Italian Asylum Seeker Center on May 2019. We outlined hereby diagnostic challenges, possible aetiologies of post-transplantation malaria and finally we summarized potential drug interactions between immunosuppressive agents and antimalarials. This report aims to increase the attention to newly arrived migrants, carefully evaluating patients coming from tropical areas and taking into consideration also rare tropical infections not endemic in final destination countries.

Modulation of Phenylalanine and Tyrosine Metabolism in HIV-1 Infected Patients with Neurocognitive Impairment: Results from a Clinical Trial.

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38+) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4+ CD38+ activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects.

Oral Bacteriotherapy in Patients With COVID-19: A Retrospective Cohort Study.

Background: Mounting evidence suggests SARS-CoV-2 may impact on host microbiota and gut inflammation, infecting intestinal epithelial cells. This possible link and its implications can be investigated by observing the effects of modulation of the microbial flora in patients with COVID-19. The aim of this study was to compare the rate of mortality, the need of ICU hospitalization and the length of hospitalization in patients with severe COVID-19 pneumonia who received the best available therapy (BAT) vs. patients treated with BAT and supplemented with oral bacteriotherapy. Methods: This retrospective, observational cohort study included 200 adults with severe COVID-19 pneumonia. All patients received therapeutic regimens including low molecular weight heparin plus one or more between hydroxychloroquine, azithromycin, antivirals, and Tocilizumab. Oral bacteriotherapy was used as complementary treatment. Results: Out of the 200 patients, 112 received BAT without oral bacteriotherapy, and 88 BAT with oral bacteriotherapy. Crude mortality was 22%. Eleven percent died in the group of patients treated with BAT plus oral bacteriotherapy vs. 30% subjects in the group of patients managed only with BAT (p < 0.001). By multivariate analysis, the age >65 years, CRP >41.8 mg/L, Platelets <150.000 mmc, and cardiovascular events were associated with the increased risk of mortality. Oral bacteriotherapy was an independent variable associated with a reduced risk for death. Despite large prospective trials are needed, this study highlights a possible role for oral bacteriotherapy in the management of patients hospitalized for COVID-19 pneumonia.

Preliminary Attempt to Predict Risk of Invasive Pulmonary Aspergillosis in Patients with Influenza: Decision Trees May Help?

Invasive pulmonary aspergillosis (IPA) is typically considered a disease of immunocompromised patients, but, recently, many cases have been reported in patients without typical risk factors. The aim of our study is to develop a risk predictive model for IPA through machine learning techniques (decision trees) in patients with influenza. We conducted a retrospective observational study analyzing data regarding patients diagnosed with influenza hospitalized at the University Hospital "Umberto I" of Rome during the 2018-2019 season. We collected five IPA cases out of 77 influenza patients. Although the small sample size is a limit, the most vulnerable patients among the influenza-infected population seem to be those with evidence of lymphocytopenia and those that received corticosteroid therapy.

Sex-related differences in markers of immune activation in virologically suppressed HIV-infected patients.

OBJECTIVES: Gender-specific studies remain a neglected area of biomedical research. Recent reports have emphasized that sex-related biological factors may affect disease progression during HIV-1 infection. The aim of this study was to investigate the influence of sex on the levels of immune activation in the gut and in peripheral blood of individuals with HIV treated with fully suppressive antiretroviral therapy (ART). METHODS: Thirty individuals with HIV undergoing long-term fully suppressive ART were enrolled in this study. Lamina propria lymphocytes (LPL) and peripheral blood mononuclear cells (PBMCs) were isolated from gut biopsies collected by pancolonoscopy and peripheral blood samples. The expression of markers of immune activation was evaluated by multi-parametric flow cytometry. This is a sub analysis of ClinicalTrials.gov Identifier: NCT02276326 RESULTS: We observed differences in the levels of immune activation in the gut and in PBMCs, with values higher in the gut compartment compared to PBMCs. In addition, we found that the mean value of the levels of immune activation was higher in the women than in the men. Finally, we measured the markers of immune activation by mean relative difference (MRD) and confirmed the higher value in the women. CONCLUSION: A significant sex-related difference in the level of immune activation was observed in a population of individuals with HIV on long-term ART. A more complete characterization of these differences may support the introduction of sex-specific approaches in the clinical management of individuals with HIV.

Real word outcomes associated with use of raltegravir in older people living with HIV: results from the 60 months follow-up of the RAL-age cohort.

Objective: In people living with HIV (PLWH), antiretroviral treatments have increased the median life expectancy. Raltegravir (RAL) represents a long-term safe regimen used both in the first-line antiretroviral treatments and in the optimization strategies. Aim of the study was to evaluate the real-life efficacy, tolerability, and safety of the long-term RAL use in a multicenter cohort of elderly PLWH.Methods: A 60-month follow-up observational study was carried out in the RAL-AGE Cohort including aged PLWH (≥60 years old) treated with RAL-based regimens (n = 96). The control group was a cohort of PLWH aged less than 60 years (n = 50).Results: RAL treated aged HIV population experiences an increase of CD4+ cells and a stable control of viral load at 60 months of follow-up. A significant improvement in lipid metabolism profile, a decrease of platelet count and a reduction in cardiovascular risk levels were observed in the older population. Immune activation markers expressed on CD4+ T cells decreased compared to baseline, but this difference was greater in the control group.Conclusion: A 60-month treatment with RAL-containing regimens is safe and highly effective in the older PLWH and these data give new insights on the elderly population.Clinical trial registration: NCT02765776 and NCT03579485.

Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19.

Background: Gastrointestinal disorders are frequent in COVID-19 and SARS-CoV-2 has been hypothesized to impact on host microbial flora and gut inflammation, infecting intestinal epithelial cells. Since there are currently no coded therapies or guidelines for treatment of COVID-19, this study aimed to evaluate the possible role of a specific oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Methods: We provide a report of 70 patients positive for COVID-19, hospitalized between March 9th and April 4th, 2020. All the patients had fever, required non-invasive oxygen therapy and presented a CT lung involvement on imaging more than 50%. Forty-two patients received hydroxychloroquine, antibiotics, and tocilizumab, alone or in combination. A second group of 28 subjects received the same therapy added with oral bacteriotherapy, using a multistrain formulation. Results: The two cohorts of patients were comparable for age, sex, laboratory values, concomitant pathologies, and the modality of oxygen support. Within 72 h, nearly all patients treated with bacteriotherapy showed remission of diarrhea and other symptoms as compared to less than half of the not supplemented group. The estimated risk of developing respiratory failure was eight-fold lower in patients receiving oral bacteriotherapy. Both the prevalence of patients transferred to ICU and mortality were higher among the patients not treated with oral bacteriotherapy. Conclusions: A specific bacterial formulation showed a significant ameliorating impact on the clinical conditions of patients positive for SARS-CoV-2 infection. These results also stress the importance of the gut-lung axis in controlling the COVID-19 disease.