Heavily treatment-experienced (HTE) individuals carry a high inflammatory burden, which is potentially increased in those with vertical HIV transmission (VT), due to lifelong viral exposure. We assessed inflammation and T-cell activation/exhaustion/senescence in HTE with VT or horizontal transmission (HT). Interleukin-6 (IL-6) was lower in VT and positively correlated with age. T-cell dysfunction was greater in HTE than people without HIV (PWOH), mainly driven by viremic VT and HT. Age and viral replication, rather than transmission mode, underlie immune dysregulation in HTE.

INTRODUCTION:Antimicrobial stewardship (AMS) is essential to tackle antimicrobial resistance. Antibiotic consumption (AC) surveillance provides evidence to guide AMS interventions. This study investigated in-hospital AC trends in Lombardy, Italy (2017-2024), with particular focus on the impact of COVID-19. METHODS:AC was expressed as DDDs per 100 bed days (absolute AC), relative proportions of Access/Watch/Reserve antibiotics (relative AC), Access-to-Watch index, and Access-to-(Watch + Reserve) index. Analyses were stratified by ward type-medical (MUs), surgical (SUs), and intensive care units (ICUs)-and timeframes: pre-COVID-19 (01/2017-02/2020), COVID-19 onset (02-03/2020), COVID-19 (03/2020-05/2023), and post-COVID-19 (05/2023-12/2024). RESULTS:Despite a surge in total AC in 2017-2024, relative Access AC rose while relative Watch AC declined, resulting in an increase of the Access-to-Watch and Access-to-(Watch + Reserve) indexes, except in ICUs. A transient reversal of such favourable trends was observed at COVID-19 onset. Nevertheless, the WHO 2023 target of ≥60% total AC being Access was not achieved; furthermore, Access-to-Watch and Access-to-(Watch + Reserve) indexes constantly remained <1, except for SUs. A downward trend in Access-to-Watch and Access-to-(Watch + Reserve) indexes was registered in the post-pandemic period. Reserve AC increased across time, periods and wards, exceeding the expected levels obtained using projections from pre-COVID-19 data. CONCLUSIONS:These findings highlight substantial shifts in in-hospital AC in Lombardy during the period 2017-2024, with concerning increases in Reserve antibiotics and an enduring failure to meet the 2023 WHO target of ≥60% Access antibiotics especially in MUs and ICUs, underscoring the need for reinforced AMS policies in the post-pandemic era.

OBJECTIVES:The aim of this study was to describe virological outcomes in people with HIV (PWH) after discontinuation of long-acting (LA) cabotegravir (CAB) plus rilpivirine (RPV). METHODS:All PWH enrolled in the Icona Cohort who discontinued CAB/RPV LA and had at least one follow-up after discontinuation were included. RESULTS:A total of 84 out of 805 (10.4%) PWH discontinued CAB/RPV, mainly due to toxicity or adverse events (67.9%). Most individuals (72.6%) returned to the same oral antiretroviral regimen used prior LA therapy. The 12-month cumulative probability of discontinuing oral ART after CAB/RPV was 19.9% (95% confidence interval [CI] 11.9-32.2%). After switching back to oral ART all individuals except one maintained or achieved HIV RNA levels below 50 copies/mL. CONCLUSION:These findings suggest that PWH who discontinue LA CAB/RPV and resume oral ART maintain or achieve high rates of virologic suppression.

BACKGROUND:The COVID-19 pandemic profoundly disrupted healthcare services. This study assessed the impact of the pandemic on the incidence, characteristics, and outcomes of late HIV diagnosis (LD) in Italy. METHODS:All people with HIV (PWH) enrolled in Italian Cohort Naïve Antiretrovirals during 2016-2019 (prepandemic) and 2021-2024 (postpandemic), and diagnosed with HIV within 3 months before enrolment, were included. LD was defined as CD4 < 350 cells/mm³ or an AIDS-defining event (ADE) within 3 months of HIV diagnosis; AIDS presentation (AIDS-P) was considered an ADE at diagnosis. Annual incidence, socio-demographic determinants, and survival outcomes were compared between periods using Poisson regression, Cox proportional hazards models, and Fine-Gray competing risk models. RESULTS:Among 5724 newly diagnosed PWH, 56% were enrolled in prepandemic and 44% postpandemic. Overall, 58% presented late and 13% as AIDS-P, with proportions stable across periods. Risk factors for LD-female sex, older age, foreign nationality, heterosexual transmission, lower education, and unemployment-remained consistent, with no significant interaction by time (P = 0.39). During follow-up, 151 deaths occurred. LD and especially AIDS-P were associated with substantially increased all-cause mortality compared with non-LD, particularly within the first-year postdiagnosis. Adjusted hazard ratios were 2.96 for LD and 6.51 for AIDS-P prepandemic, and 8.64 and 17.99 postpandemic. No excess risk was observed for non-AIDS-related mortality. CONCLUSION:The prevalence and determinants of LD and AIDS-P in Italy remained stable before and after the COVID-19 pandemic. However, late presentation continues to carry a heavy mortality burden, underscoring the urgent need to strengthen early testing and prompt linkage to care.

BACKGROUND:Although COVID-19 is no longer a public health emergency, it remains the most prevalent circulating infectious-like-illness in Europe. Whether immunocompromising conditions (ICCs) still carry increased mortality risk during the Omicron era is unclear. METHODS:We conducted a cohort study across EuCARE sites in 8 countries among adults admitted to hospital with COVID-19 between 2020-2023. ICCs and COVID-19 pneumonia at hospitalization were defined using clinical information and ICD-10 codes. Logistic regression and counterfactual mediation analysis was used to compare 28-day in-hospital mortality risk associated with ICCs using COVID-19 pneumonia and vaccination at hospital entry as intermediates. Proportion of the total effect of ICCs mediated and the controlled direct effects (CDEs) were calculated. We also formally tested for interaction between SARS CoV-2 variants and ICCs for mortality risk. FINDINGS:42,488 individuals were included, of which 1,675 (3.9%) had an ICC. 55% were male, median (IQR) age was 67 (52, 79) years. Overall, 4,344 (10.2%) individuals died in hospital. ICCs were associated with increased mortality, OR = 1.49 (1.25, 1.79) with no evidence for an attenuation during the Omicron phase (p-interaction=0.60). Mediation analyses showed that the total effect of ICCs was mediated by vaccination but only weakly by pneumonia. With Omicron, the excess mortality associated with ICC was higher under the scenario that everyone in the cohort was to develop COVID-19 pneumonia [CDE =1.22 (0.09, 1.65)]. INTERPRETATION:ICC remains a significant risk factor for in-hospital death, even during the Omicron era, particularly if the infection led to the development of pneumonia.

BACKGROUND:Among people with HIV (PWH) on antiretroviral therapy (ART), serious non-AIDS-events (SNAEs) are linked to inflammation. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) are inflammatory biomarkers. We investigated their performance in PWH. METHODS:PWH enrolled in the national cohort Italian Cohort Naive Antiretrovirals who started ART over 1997-2021 with measures of NLR, PLR, and/or LMR within 6 months pre-ART ("baseline") were included. Biomarkers were grouped using tertiles of their distribution (Q1, Q2, and Q3). Association between baseline biomarkers values and risk of SNAEs, AIDS, and all-cause mortality were tested using Kaplan-Meier and Cox proportional hazard models adjusting for baseline age, CD4 + count, human immunodeficiency virus-ribonucleic acid (HIV-RNA), HCV-status, and year of starting ART. RESULTS:We included 9248, 8727, and 1090 individuals in the PLR, NLR, and LMR analyses, respectively: 77% male, median age 38. Baseline PLR, NLR, and LMR mean values were 248.9, 2.7, and 8.2, respectively. After adjusting for confounders, the risk of SNAEs was higher for Q1-PLR vs Q2 and Q3 [adjusted-hazard ratio (HR) 0.76 (95% CI: 0.64 to 0.90) and 0.78 (95% CI: 0.66 to 0.94), respectively], and mortality [adjusted-HR 0.54 (95% CI: 0.41 to 0.70), and 0.68 (95% CI: 0.53 to 0.87), respectively], and the risk of AIDS was lower for Q2-PLR (adjusted-HR = 0.74, 95% CI: 0.60 to 0.90). Mortality was higher for Q3-NLR [adjusted-HR 1.32 (95% CI: 1.01 to 1.72)]. Q1-LMR showed higher risks of SNAEs, AIDS, and mortality, but this weakened after adjusting for confounders. CONCLUSIONS:A baseline PLR below 93.2 was associated with SNAEs, AIDS, and mortality, and NLR above 2.04 was associated with mortality. Derived from routinely collected blood parameters, PLR, and NLR may help clinicians identifying PWH at risk of poor outcomes.

OBJECTIVE:Despite suppressive antiretroviral therapy (ART), people with HIV (PWH) frequently experience neurocognitive impairment, yet underlying mechanisms remain elusive. We hereby evaluated biomarkers of brain injury, inflammation and gut barrier dysfunction to identify factors associated with cognitive performance in PWH. DESIGN:PWH on suppressive ART and people without HIV (PWoH) were cross-sectionally enrolled. METHODS:PWH underwent a comprehensive neurocognitive assessment and HIV-associated neurocognitive disorder (HAND) was diagnosed. We measured plasma markers of neuroaxonal damage and astrocyte activation (NF-L/GFAP by Simoa), inflammation/monocyte activation (IP-10/IL-6/sCD14 by ELISA), gut barrier disruption (I-FABP/E-cadherin/zonulin by ELISA) and microbial translocation (LBP/EndoCAb IgG by ELISA). Non-parametric tests and multivariable regression were used for analyses. RESULTS:Forty PWH [17 HAND+ (asymptomatic neurocognitive impairment), 23 HAND-] and 10 PWoH were included. Compared to PWoH, PWH had higher levels of inflammation/monocyte activation (IP-10/sCD14), gut barrier disruption (I-FABP) and microbial translocation (LBP/EndoCAb-IgG). PWH HAND+ showed higher levels of GFAP/IL-6/sCD14 compared to PWH HAND-. At logistic regression adjusting for age, sex and CD4 T-cell nadir , HAND confirmed associated with higher GFAP/sCD14. More specifically, at linear regression adjusting for the same variables, higher GFAP levels were associated with lower global cognitive performance, worse attention and working memory, speed of information processing, motor skills, as well as learning and memory; higher IL-6 with worse abstraction and executive functions; higher IL-6 and sCD14 with worse verbal fluency. CONCLUSION:In our cohort of ART-suppressed PWH, asymptomatic neurocognitive impairment was associated with markers of astrocyte/monocyte activation and inflammation rather than with markers of neuroaxonal damage, gut barrier disruption, or microbial translocation.

OBJECTIVES:Multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a major global health threat, with limited therapeutic options and high morbidity and mortality. Cefiderocol, a novel siderophore cephalosporin, has emerged as a potential treatment for MDR-GNB infections. This narrative review aims to critically appraise evidence from randomised controlled trials (RCTs) and real-world studies to clarify the clinical effectiveness, safety, and optimal place-in-therapy of cefiderocol in the management of MDR-GNB infections. METHODS:A narrative review of phase 2 and 3 RCTs and available real-world observational studies was performed. Evidence was synthesised focusing on mechanism of action, pharmacokinetic/pharmacodynamic properties, resistance mechanisms, and clinical outcomes across different infection sites, pathogens, and treatment strategies. RESULTS:RCTs demonstrated non-inferiority of cefiderocol compared with standard-of-care therapies in complicated urinary tract infections, nosocomial pneumonia, and bloodstream infections sustained by GNB. However, heterogeneous outcomes and mortality imbalances were observed in specific subgroups, particularly in Acinetobacter baumannii and metallo-β-lactamase (MBL)-producing pathogens. Real-world studies support cefiderocol use in critically ill patients, ventilator-associated pneumonia, and bloodstream infections, with more consistent benefits observed for Pseudomonas aeruginosa and carbapenem-resistant Enterobacterales. Outcomes in carbapenem-resistant A. baumannii infections remain variable. Early initiation of therapy appears associated with improved outcomes, while no clear superiority of combination therapy over monotherapy has been established. CONCLUSIONS:Cefiderocol represents a valuable option for the treatment of MDR-GNB infections. Its optimal use requires careful patient and pathogen selection, early administration, and integration within antimicrobial stewardship strategies. Further pathogen- and infection-specific trials are needed to better define its role, particularly in carbapenem-resistant A. baumannii and MBL-producing infections.

Background:Altered adipose tissue biology plays a key role in the development of cardiovascular disease (CVD) and cancer and contributes to mortality. We assessed the association between obesity in people with HIV (PWH) at antiretroviral therapy (ART) initiation and the risk of clinical events. Methods:In this prospective cohort study, we included ART-naïve adults PWH enrolled in the Italian Cohort Naive Antiretrovirals (Icona) Foundation study cohort in Italy across 96 sites between January 1997 and July 2025. Participants were included if they initiated ART, had body mass index (BMI) > 18.5 kg/m2, and were free from AIDS, CVD, and cancer at ART initiation. Participants were classified as having obesity, defined as BMI ≥ 30 kg/m2, or not having obesity, defined as BMI 18.5-29.9 kg/m2, at ART initiation. The primary outcome was the first occurrence of CVD, cancer, or death. We performed a standard survival analysis with time-fixed covariates at baseline with a composite outcome of CVD/cancer/death. We hypothesized that age may be an effect measure modifier: results are presented after stratification by age (young [18-30], middle aged [31-60] and older [>60 years]). Findings:A total of 11,652 PWH (20.7% females, median age 38 years [Inter Quartile Range (IQR): 31, 46]) were included: 11,005 (94.4%) were people without obesity and 647 (5.6%) people with obesity. A total of 837 events were recorded: 122 CVD, 374 cancers and 341 deaths. By 15 years from ART initiation, the risk of CVD/cancer/death was 19.1% in people with obesity (95% Confidence Interval [CI]: 14.1-24.9%) vs. 12.4% in people without obesity (95% CI:11.3-13.4%, log-rank p = 0.0029). After controlling for confounding, the difference was attenuated (adjusted hazard ratio [aHR] 1.28 [95% CI:0.98-1.67], p = 0.073). Although we did not find evidence for interaction (p-value = 0.758) there was a trend for a larger effect among younger PWH: young (aHR 1.83 [95% CI 0.74, 4.56]), middle aged (aHR 1.49 [95% CI 1.11, 2.00]) and older (aHR 1.20 [95% CI 0.60, 2.41]). Interpretation:Obesity at ART initiation may be associated with a clinically meaningful increase in the risk of CVD, cancer, and death. We found weak evidence of a possible age-related gradient, with larger effect size in PWH under 60 years of age, which warrants further investigation. Funding:The Italian Cohort Naive Antiretrovirals (Icona) Foundation Study is supported by unrestricted grants from Gilead Sciences, ViiV Healthcare, Merck Sharpe & Dohme.

Background How post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms. Methods We conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks. Results Among 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were not significantly more frequent than in other acute respiratory viral infections. Conclusions Our findings support the concept of PCC as one example within the broader spectrum of PAIS, underscoring the need to recognize these conditions after non-COVID respiratory viral infections and to further investigate shared and pathogen-specific mechanisms.

Dolutegravir/lamivudine (DTG/3TC), used as a two-drug regimen (2DR), has demonstrated non-inferiority to traditional three-drug regimens (3DRs) in treatment-naive people with HIV (PWH), with sustained virological efficacy, favorable tolerability, and a good safety profile. However, its implementation in routine clinical practice raises several questions, particularly in populations underrepresented in registration trials. This review critically appraises current evidence supporting DTG/3TC as first-line antiretroviral therapy, drawing from randomized clinical trials and real-world studies. Available data indicate that DTG/3TC maintains high virological suppression rates even in individuals with high baseline viral load (>500,000 copies/mL), with no emergent resistance. Evidence from test-and-treat settings suggests comparable efficacy to triple therapy, provided that hepatitis B coinfection and transmitted resistance are adequately excluded. Preliminary data in late presenters and those with advanced disease support its effectiveness, although confirmatory trials are warranted. Beyond viro-immunological outcomes, DTG/3TC appears equivalent to triple regimens in reducing viral reservoirs, immune activation, and systemic inflammation. Evidence in women living with HIV, including during pregnancy, remains limited but reassuring, with no major safety concerns identified. Overall, the body of clinical and real-world evidence supports DTG/3TC as a simplified and durable first-line regimen for most treatment-naive PWH. Ongoing research should further define its role in acute infection, advanced HIV disease, and specific subpopulations such as women and individuals from regions with high prevalence of non-B subtypes.

Background and objectives Acute bacterial skin and skin structure infections (ABSSSI) are common infections associated with relevant clinical and organizational burden. Their management requires appropriate antibiotic therapy and integrated healthcare organization; however, real-world practices remain heterogeneous. The objective was to explore current clinical and organizational practices in ABSSSI management across expert Italian centres, identifying strengths, critical issues, and unmet needs through a multicentre survey with expert interpretation.Methods A structured 107-item questionnaire was administered via e-mail to 9 Italian centres with consolidated experience in ABSSSI management. A single senior specialist provided a comprehensive response for each centre. Findings were subsequently discussed by a multidisciplinary group of key opinion leaders to contextualize results and identify priority areas for improvement.Results Marked heterogeneity was observed across centres in organizational models and care pathways. Infectious Diseases specialists were central to management, although 24/7 availability was limited. Access to microbiology services and vulnology support varied across centres. No centre reported fully structured ABSSSI care pathways, although informal internal manuals were common. Dedicated multidisciplinary teams were present in a minority of centres. Structured communication with general practitioners and defined hospital-to-community pathways were generally lacking. Monitoring systems and dedicated databases were inconsistently implemented, with limited pharmacoeconomic evaluation.Conclusions This multicentre survey highlights substantial variability in ABSSSI management across Italian expert centres, with key gaps in care pathways, specialist availability, and data collection. Addressing these issues may improve standardization and efficiency of care.

Background:HIV reservoirs, dysregulated cytokine profile, and gut barrier damage persist despite suppressive combination antiretroviral therapy (cART). Whether initiating cART during primary HIV infection (PHI) mitigates these pathological processes remains unclear. Methods:We studied 55 individuals with PHI at baseline (T0), after 12 (T12), and 48 weeks (T48) of cART, 18 individuals with chronic HIV infection (CHI) and 10 sex-matched people without HIV (PWOH). Total HIV DNA was measured in peripheral blood mononuclear cells (PBMCs) using ddPCR, while cytokines profiles (IL-2, IL-4, TNF-α, IFN-γ) were measured in plasma by Luminex and antigen-specific T-cell responses were assessed in PBMCs of a subset of participants by intracellular cytokine staining. Microbial translocation markers (EndoCab, 1,3-β-D-glucan, lipopolysaccharide-binding protein [LBP], soluble CD14 [sCD14]) and gut barrier integrity markers (E-cadherin, I-FABP) were measured in plasma by ELISA, at each corresponding time point. Statistical analyses included Friedman tests with Dunn's multiple comparisons, Wilcoxon paired tests, and Mann-Whitney tests, as appropriate. Results:At baseline, both groups displayed a cytokine profile characterized by elevated IL-4 levels compared with PWOH, with individuals with PHI showing significantly higher IL-2 levels and comparable IFN-γ and TNF-α levels to individuals with CHI. Over 48 weeks of cART, IL-4 and IL-2 declined only in individuals with PHI, yet, remained elevated compared with PWOH, whereas cytokine levels remained largely stable in individuals with CHI. Conversely, antigen-specific CD4⁺ T-cell responses remained mainly Th1-skewed, with minimal IL-4 production. Individuals with PHI showed lower baseline sCD14, comparable to PWOH, which further declined during cART, whereas sCD14 remained elevated in individuals with CHI compared with PWOH. Markers of microbial translocation (LBP, 1,3-β-D-glucan) remained stable in individuals treated in PHI and comparable to PWOH but increased in individuals treated in CHI over time. E-cadherin levels were consistently lower in individuals with PHI, similar to PWOH. In contrast, I-FABP showed a non-significant decline over time only in individuals with PHI, while remaining higher in both individuals with PHI and CHI compared with PWOH. Conclusions:Early cART initiation in individuals with PHI reduces viral reservoirs and limits gut barrier disruption and microbial translocation but fails to restore the systemic cytokine landscape compared with PWOH. These findings support the benefits of prompt treatment initiation during acute infection to limit HIV reservoir size and preserve mucosal integrity.

Modern ART is evolving, allowing the use of new drug formulations and alternative routes of administration to oral therapy. Long-acting (LA) cabotegravir and rilpivirine, the first fully injectable antiretroviral regimen approved for clinical use, is a test case for this new route of administration, and an innovation with implications for the quality of life of people with HIV (PWH). However, its use requires a reorganization of outpatient clinics and outpatient services, and a number of issues remain to be defined regarding the management of PWH on LA drugs, including the correct selection of people who can be treated with LA cabotegravir and rilpivirine. There is also ongoing debate about the best way to monitor both efficacy and tolerability of LA treatment and whether the management of virological failures and blips should be different from that reserved for oral regimens. The present article reviews the data on the use and management of LA cabotegravir and rilpivirine in different settings, with a review of clinical trial data and also the first available real-life experiences. The article focuses on the following: the reasons for the use of LA drugs; the implementation of their use in clinical practice; and the monitoring of treated people over time.

Post COVID-19 condition (PCC) affects 10–40

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. Acute complications may impact on disease progression but their prevalence is unclear and prognostic outcomes of complicated patients have been poorly studied. The aim of the study was to estimate the prevalence of acute complications of TB at the time of diagnosis. Short-term outcomes were also evaluated. A cross-sectional study was carried out in Milan (Italy), from January 2018 to December 2023. 201 patients with TB were recruited. 88 complications were recorded in 65 (32.3