HIV screening of migrants in the autonomous Province of Trento (North-Eastern Italy).

Abstract: Migrants have accounted for more than 40% of new HIV diagnoses in Europe in 2022. Among the population of asylum seekers currently present in the Trento Province, screening for HIV infection is poorly carried out for various reasons. Here we report our experience about screening for HIV infection in asylum seekers present in that area using rapid self HIV-testing.

Short-cycle therapy in HIV-infected adults: rilpivirine combination 4 days on/3 days off therapy.

BACKGROUND: Short-cycle therapy (SCT) is the administration of ART for 4 or 5 consecutive days a week, followed by 3 or 2 days off therapy. Its benefits include improving patient satisfaction and reducing ART toxicity and costs. METHODS: In this observational study we included HIV-infected adults with a three-drug ART containing rilpivirine, a history of long-term virological suppression and no evidence of resistance to previous drug regimens. Patients switched to a SCT of 4 days on/3 days off and were followed for 48 weeks with regular check-ups. The primary outcome was virological suppression; secondary outcomes were changes in CD4+ cells and rilpivirine plasma concentration, the occurrence of adverse events and resistance in the case of failure, and patient satisfaction. RESULTS: At week 48 no virological failure was observed, with a virological suppression rate of 30/30 (100%). Three patients switched back to continuous therapy for other reasons, with an overall success rate of SCT of 30/33 (90.9%, 95% CI = 81.24% to 100%). The CD4+ mean value increased by +64 cells/mm3 (95% CI = -59 to +187 cells/mm3; P = 0.052). No adverse events were observed and the mean total score in the satisfaction questionnaire was 57.7/60 (96.22%). Rilpivirine plasma concentration was below the efficacy threshold in 71.3% of the samples, suggesting that the patients' characteristics, more than the drug's pharmacokinetics, played a role in maintaining virological suppression. CONCLUSIONS: SCT with rilpivirine-containing regimens could be an effective alternative to continuous therapy in selected HIV-infected patients with previous long-term virological suppression.

Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study.

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants.

Benign acute viral myositis in African migrants: A clinical, serological, and pathological study.

BACKGROUND: Several viruses have been described as causes of acquired inflammatory myopathies; however, the mechanisms by which they cause muscle disease are still unclear. The aim of this study was to describe the laboratory features of benign acute myositis in a small case series. METHODS: A detailed pathological and serological analysis was performed in five African migrants who developed an acute viral myositis complicated by rhabdomyolysis. RESULTS: Muscle biopsies clearly documented an inflammatory myopathy with histological features similar to polymyositis including CD8+ T cells surrounding and invading nonnecrotic muscle fibers, CD68+ macrophages and major histocompatibility complex class I antigen upregulation. In addition, positivity for myositis-specific antibodies (MSA), in particular anti-aminoacyl tRNA synthetases, was found in the serum of two patients. CONCLUSIONS: Our study demonstrated that T-cell mediated injury occurs in muscle of patients with acute viral myositis, and that MSA may be present in the serum of these patients.

Immunovirological outcome and HIV-1 DNA decay in a small cohort of HIV-1-infected patients deintensificated from Abacavir/Lamivudine/Dolutegravir to Lamivudine plus Dolutegravir.

Combination abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) is approved as a first-line treatment for antiretroviral naïve patients. This report investigated the immunovirological outcome and total HIV-1 DNA decay in a small cohort of naïve HIV-1-positive patients treated with this regimen. In the presence of viral suppression and increased lymphocyte T CD4+ cells, the quantitative analysis of total HIV-1 DNA content revealed a significant decay after 12 months of treatment. Subsequently, we deintensificated the treatment of these patients from (ABC/3TC/DTG) to lamivudine plus dolutegravir (3TC/DTG) after 12 months of virological suppression, as a strategy of "induction-maintenance" therapy. The analysis of HIV-1 RNA viral load, total HIV-1 DNA, CD4+ T lymphocyte count and CD8+ HLA-DR+ T lymphocyte percentage after a mean 3.5 months of therapy deintensification showed no significant difference with respect to data detected after 12 months of ABC/3TC/DTG treatment in the presence of continuous viral suppression. These results indicate that the deintensification of highly active antiretroviral therapy (HAART) from ABC/ 3TC/DTG to 3TC/DTG effectively controls HIV-1 replication and in the early period does not induce any significant variations of total HIV-1 DNA. This suggests that HAART deintensification might be proposed as a therapeutic evolution in the treatment of HIV-1 infection.

Short Cycle, Intermittent Therapy: A Valuable Option in Selected, Virologically Suppressed People Living with HIV.

The use of long-acting antiretroviral regimens will not be suitable for all people living with HIV for various reasons (previous virological failure with drugs of the same class, side effects, logistic difficulties, and costs). We think that short-cycle therapies could represent a feasible and valuable option for antiretroviral treatment optimization in selected individuals. So here we review clinical evidence about efficacy of short-cycle therapy in suppressed HIV-infected patients.

Cardiovascular Drug Interactions with Nirmatrelvir/Ritonavir for COVID-19: Considerations for Daily Practice.

Cardiovascular disease is associated with progression to severe COVID-19 and patients with the condition are among those in whom early antiviral therapy should be warranted. The combination of nirmatrelvir/ritonavir (Paxlovid®) has been approved for clinical use by the Food and Drug Administration and European Medicines Agency. Because patients with cardiovascular disease are often on polypharmacy, physicians need to be aware of potential drug-drug interactions (DDIs) when treating COVID-19 with nirmatrelvir/ritonavir. Guidance is given for avoiding DDIs, emphasising that preventing and managing potential DDIs with nirmatrelvir/ritonavir requires thorough assessment and knowledge. The present review summarises the clinical pharmacology of nirmatrelvir/ritonavir and provides details on potential DDIs with a focus on daily practice in patients with cardiovascular disease. Particular attention is needed for drugs that are predominantly metabolised by cytochrome P450 3A4, are substrates of P-glycoprotein and have a narrow therapeutic index. Proper management of potential DDIs must balance the benefit of nirmatrelvir/ ritonavir to prevent severe disease with the risk of serious adverse events.

The diagnostic yield of the Meares & Stamey test can be significantly improved by symptom-based patient selection and the experience of the test performer.

BACKGROUND: Even if Meares-Stamey 4-glass (M&S) test is regarded a decisive tool for diagnosing prostatitis its use is only rarely performed in everyday clinical practice. Here, we analyze if the diagnostic yield of the M&S test could be improved by a pre-test categorization of patients due to undergo a M&S test. METHODS: All clinical and microbiological data of patients who underwent M&S test in two urological centers from January 2004 to December 2021 were analyzed in this retrospective cohort study. One center has a dedicated staff member for the study of prostatitis (Cohort I), while the other center is a general urological unit (Cohort II). All patients were divided into 3 groups on the basis of the assembled data: patients with symptoms related to prostatitis only (Group I), patients with symptoms related to both prostatitis and BPH (Group II), patients with symptoms related to BPH only (Group III). The rates of positive microbiological results in each group were compared. RESULTS: In the whole period, 9347 patients were analyzed and categorized as follows: Group I, 1884; Group II, 5151; Group III, 2312. Three-thousand and eight-hundred twenty-three patients showed positive culture results (40.9%). The most common isolated species was Escherichia coli (49.7%), followed by Enteroccus spp. (31.8%). The rates of positive M&S tests in the different symptom groups were: Group I, 1532 (81.4%); Group II, 1494 (29.0%); Group III, 797 (34.4%). The overall rate of positive M&S tests in each urology center showed that the center with a staff member who is dedicated to prostatitis studies (Cohort I) had a significantly higher rate of positive M&S tests than the general urological department (Cohort II) (64.3% vs 31.4%; p < 0.001). CONCLUSIONS: Symptom-based patient selection and dedicated staff members will increase the diagnostic yield of the M&S test and reduce the number of unnecessary tests.

Profiles of primary brain abscesses and their impact on survival: An international ID-IRI study.

OBJECTIVES: This study of 331 primary brain abscess (PBA) patients aimed to understand infecting agents, predisposing factors, and outcomes, with a focus on factors affecting mortality. METHODS: Data were collected from 39 centers across 16 countries between January 2010 and December 2022, and clinical, radiological, and microbiological findings, along with their impact on mortality, were analyzed. RESULTS: The patients had a mean ± SD age of 46.8 ± 16.3 years, with a male predominance of 71.6%. Common symptoms included headache (77.9%), fever (54.4%), and focal neurological deficits (53.5%). Gram-positive cocci were the predominant pathogens, with Viridans group streptococci identified as the most frequently isolated organisms. All patients received antimicrobial therapy and 71.6% underwent interventional therapies. The 42-day and 180-day survival rates were 91.9% and 86.1%, respectively. Significant predictors of 42-day mortality included intravenous drug addiction (HR: 6.02, 95% CI: 1.38-26.26), malignancy (HR: 3.61, 95% CI: 1.23-10.58), confusion (HR: 2.65, 95% CI: 1.19-5.88), and unidentified bacteria (HR: 4.68, 95% CI: 1.76-12.43). Significant predictors of 180-day mortality included malignancy (HR: 2.70, 95% CI: 1.07-6.81), confusion (HR: 2.14, 95% CI: 1.11-4.15), temporal lobe involvement (HR: 2.10, 95% CI: 1.08-4.08), and unidentified bacteria (HR: 3.02, 95% CI: 1.49-6.15). CONCLUSION: The risk of death in PBA extends beyond the infection phase, with different factors influencing the 42-day and 180-day mortality rates. Intravenous drug addiction was associated with early mortality, while temporal lobe involvement was associated with late mortality.

Successful treatment of persistent SARS-CoV-2 infection with nirmatrelvir/ritonavir plus sotrovimab in four immunocompromised patients.

Immunocompromised patients with leukemia/lymphoma often have a suboptimal response to vaccination against SARS-CoV-2 and, if infected, can develop a persistent infection.SARS-CoV-2 PCR was performed on nasopharingeal swabs and serum IgG anti-SARS-CoV-2 trimeric spike glycoprotein antibodies were measured during persistence of infection. Treatment with a combination of nirmatrelvir/ritonavir plus sotrovimab led to viral clearance in three patients with leukaemia or lymphoma with persistent SARS-CoV-2 and negative SARS-CoV-2 antibody tests. No standardized treatments for persistent infection with SARS-CoV-2 infection are available. We have reported the viral clearance in two immunocompromised patients treated with antiviral drug nirmatrelvir/ritonavir and monoclonal antibody sotrovimab. We suggest that this strategy should be tested in clinical trials to find the right strategy for a clinical problem with public health implications to SARS-CoV-2 evolution and immune escape in these sub-set of patients.

Acceptability of Switching to Long-Acting Cabotegravir and Rilpivirine Among People Living with HIV on Dolutegravir/Rilpivirine Combination: A Single-Center Experience.

The availability of long-acting cabotegravir and rilpivirine injection combination requires some changes in service delivery of outpatient HIV clinics; it is therefore important for clinicians to know the potential number of people living with HIV (PLWH) who are interested in a long-acting antiretroviral treatment. We aimed to determine in an outpatient clinic the number of PLWH, on dolutegravir/rilpivirine, accepting a switch to an injectable long-acting antiretroviral treatment, and the reasons underlying this choice. In our single-center study, in this subset of HIV-infected patients, the main cause for refusal of a long-acting injectable regimen was the need for the administration to be done in hospital, as required in Italy, suggesting that current regulations about this aspect must be changed.

Antibiotic Resistance Patterns Among Uropathogens in Female Outpatients Affected by Uncomplicated Cystitis: Focus on Fosfomycin Trometamol.

OBJECTIVES: To report the resistance rate against fosfomycin trometamol among outpatient women with symptoms related to urinary tract infections over a 6-year period in a multicentre, cross-sectional study. METHODS: Urinary samples were collected from three high-volume laboratories from January 2015 to December 2020. The pattern of resistance to fosfomycin was analysed by using the Vitek II automated system. RESULTS: A total of 7289 urinary samples were collected and 8321 strains were analysed during the study period. The most commonly isolated uropathogen was Escherichia coli (n = 6583, 79.1%). The mean resistance rate against fosfomycin was 9.7% (range 7.1-11.3). No statistically significant difference was found between the three laboratories (P = 0.53). There was no significant increase in resistance rate during the study period. The mean resistance rate against fosfomycin was higher among extended-spectrum ß-lactamase (ESBL)-producing bacteria when compared with non-ESBL-producing strains (10.8% vs. 7.9%; P < 0.001). CONCLUSION: Uropathogens isolated from women affected by cystitis remained highly susceptible to fosfomycin. These findings confirm recommendations in international guidelines that advocate fosfomycin trometamol for empirical treatment of uncomplicated cystitis in women.

Real-life comparison of mortality in patients with SARS-CoV-2 infection at risk for clinical progression treated with molnupiravir or nirmatrelvir plus ritonavir during the Omicron era in Italy: a nationwide, cohort study.

Background: Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era. Methods: Data collected in the nationwide, population-based, cohort of patients registered in the database of the Italian Medicines Agency (AIFA) were used. To increase completeness of the recorded deaths and date correctness, a cross-check with the National Death Registry provided by the Ministry of the Interior was performed. We included in this study all patients infected by SARS-CoV-2 treated within 5 days after the test date and symptom onset between February 8 and April 30, 2022. All-cause mortalities by day 28 were compared between the two treatment groups after balancing for baseline characteristics using weights obtained from a gradient boosting machine algorithm. Findings: In the considered timeframe, 17,977 patients treated with molnupiravir and 11,576 patients with nirmatrelvir plus ritonavir were included in the analysis. Most patients (25,617/29,553 = 86.7%) received a full vaccine course including the booster dose. A higher crude incidence rate of all-cause mortality was found among molnupiravir users (51.83 per 100,000 person-days), compared to nirmatrelvir plus ritonavir users (22.29 per 100,000 person-days). However, molnupiravir-treated patients were older than those treated with nirmatrelvir plus ritonavir and differences between the two populations were found as far as types of co-morbidities were concerned. For this reason, we compared the weight-adjusted cumulative incidences using the Aalen estimator and found that the adjusted cumulative incidence rates were 1.23% (95% CI 1.07%-1.38%) for molnupiravir-treated and 0.78% (95% CI 0.58%-0.98%) for nirmatrelvir plus ritonavir-treated patients (adjusted log rank p = 0.0002). Moreover, the weight-adjusted mixed-effect Cox model including Italian regions and NHS centers as random effects and treatment as the only covariate confirmed a significant reduced risk of death in patients treated with nirmatrelvir plus ritonavir. Lastly, a significant reduction in the risk of death associated with nirmatrelvir plus ritonavir was confirmed in patient subgroups, such as in females, fully vaccinated patients, those treated within day 2 since symptom onset and patients without (haemato)-oncological diseases. Interpretation: Early initiation of nirmatrelvir plus ritonavir was associated for the first time with a significantly reduced risk of all-cause mortality by day 28 compared to molnupiravir, both in the overall population and in patient subgroups, including those fully vaccinated with the booster dose. Funding: This study did not receive funding.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Features of Mpox infection: The analysis of the data submitted to the ID-IRI network.

Background: Mpox is a rare zoonotic disease caused by the Mpox virus. On May 21, 2022, WHO announced the emergence of confirmed Mpox cases in countries outside the endemic areas in Central and West Africa. Methods: This multicentre study was performed through the Infectious Diseases International Research Initiative network. Nineteen collaborating centres in 16 countries participated in the study. Consecutive cases with positive Mpoxv-DNA results by the polymerase chain reaction test were included in the study. Results: The mean age of 647 patients included in the study was 34.5.98.6% of cases were males, 95.3% were homosexual-bisexual, and 92.2% had a history of sexual contact. History of smallpox vaccination was present in 3.4% of cases. The median incubation period was 7.0 days. The most common symptoms and signs were rashes in 99.5%, lymphadenopathy in 65.1%, and fever in 54.9%. HIV infection was present in 93.8% of cases, and 17.8% were followed up in the hospital for further treatment. In the two weeks before the rash, prodromal symptoms occurred in 52.8% of cases. The incubation period was 3.5 days shorter in HIV-infected Mpox cases with CD4 count <200/µL, we disclosed the presence of lymphadenopathy, a characteristic finding for Mpox, accompanied the disease to a lesser extent in cases with smallpox vaccination. Conclusions: Mpox disseminates globally, not just in the endemic areas. Knowledge of clinical features, disease transmission kinetics, and rapid and effective implementation of public health measures are paramount, as reflected by our findings in this study.