ABSTRACT Cefepime/enmetazobactam (FEP/META) is a novel β-lactam/β-lactamase inhibitor combination with activity against Enterobacterales, including extended-spectrum β-lactamase-producing isolates, but real-world clinical data outside randomized trials remain limited. We conducted a retrospective multicenter descriptive study across 13 Italian hospitals. Eligible patients had infections caused by Enterobacterales and received ≥72 h of cefepime/enmetazobactam therapy (alone or in combination with other antimicrobials) under a compassionate-use program. Thirty-two patients were included. The most frequently isolated pathogens were Escherichia coli (16/32, 50.0%) and Klebsiella pneumoniae (13/32, 40.6%). Extended-spectrum β-lactamase production was documented in 29/32 isolates (90.6%), while β-lactam/β-lactamase inhibitor resistance and fluoroquinolone resistance were each observed in 18/32 isolates (56.2%). Four isolates were ertapenem-resistant but remained susceptible to imipenem and meropenem; no carbapenemase production was confirmed. FEP/META was safely administered as targeted therapy in most cases and was used both as monotherapy and in combination regimens, according to clinical severity and source of infection. Clinical cure was achieved in all patients, and microbiological eradication was documented in 25/32 cases (78.1%). No in-hospital deaths were recorded. Despite the inherent limitations of retrospective real-world studies, our findings suggest that cefepime/enmetazobactam may be a well-tolerated component of carbapenem-sparing treatment strategies for selected documented Enterobacterales infections. In 32 real-world documented Enterobacterales infections, cefepime/enmetazobactam achieved 100% clinical cure and 78.1% microbiological eradication, with favorable tolerability. IMPORTANCE Antibiotic-resistant infections are an increasing challenge, and clinicians need effective treatments that can reduce reliance on carbapenems, which are often considered last-line antibiotics. Cefepime/enmetazobactam is a new antibiotic combination with activity against resistant Enterobacterales, particularly ESBL-producing bacteria, but real-world clinical data remain limited. This multicenter Italian study describes its use in 32 patients with Enterobacterales infections, including urinary tract, bloodstream, and respiratory infections. Clinical cure was achieved in all patients, microbiological eradication was documented in most cases, and no in-hospital deaths occurred. These findings suggest that cefepime/enmetazobactam may be a useful and well-tolerated carbapenem-sparing option for selected resistant gram-negative infections, while emphasizing the need for larger studies to confirm its role in routine clinical practice.

ABSTRACT Actinic keratosis (AK) is a common premalignant skin condition associated with chronic ultraviolet exposure and an increased risk of progression to cutaneous squamous cell carcinoma (cSCC). Its prevalence rises with age and is influenced by multiple factors, including fair skin phototype and immunosuppression. People living with human immunodeficiency virus (HIV) are at increased risk of cSCC due to impaired immune surveillance, highlighting the importance of early diagnosis and effective management of AK in this population. However, data on optimal treatment strategies in individuals with HIV remain limited. Among available therapies, topical 5‐fluorouracil (5‐FU) is considered one of the most effective field‐directed treatments. We describe the case of a 70‐year‐old man with well‐controlled HIV infection who presented with multiple facial actinic keratoses in a field of cancerization. The patient had previously undergone several treatments, including cryotherapy, diclofenac gel, and tirbanibulin, with only temporary improvement. Given the extent of the lesions and prior therapeutic failure, topical 5‐FU 4% cream was initiated once daily for 28 days. During treatment, the patient developed a moderate inflammatory reaction characterized by erythema and pruritus, which was expected and did not require discontinuation. At the 3‐month follow‐up, complete clinical clearance of the lesions was achieved. This case supports the efficacy and acceptable tolerability of topical 5‐FU 4% in the treatment of AK in a patient living with HIV, even after previous treatment failure. The results are consistent with existing evidence supporting the use of 5‐FU as a first‐line field therapy. Given the increased oncologic risk in immunocompromised patients, timely and effective treatment of AK is essential. Nevertheless, the limited evidence available in this specific population underscores the need for further prospective studies to better define management strategies and long‐term outcomes.

BACKGROUND/OBJECTIVES:Among the antiretroviral therapies (ARTs) recently introduced for people living with HIV (PLWH), the fixed-dose combination of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) became reimbursable in Italy in June 2019. METHODS:This study evaluated drug utilization, healthcare resource consumption and direct costs among ART-naïve adults initiating B/F/TAF or other non-bictegravir-based regimens, identified from June 2019 to September 2022 within administrative databases of healthcare entities covering approximately nine million citizens. Baseline clinical characteristics at first ART prescription were compared across B/F/TAF-treated patients, those receiving other ART regimens, and non-HIV controls, while treatment outcomes during follow-up were evaluated among PLWH receiving B/F/TAF or other ARTs; healthcare consumption and costs were assessed after propensity score matching within the PLWH cohorts only. RESULTS:Overall, 374 individuals initiated B/F/TAF and 5576 other ARTs. Patients treated with B/F/TAF showed greater adherence and persistence, with multivariate analyses confirming a lower risk of discontinuation or switching (HR = 0.66, 95% CI 0.57-0.76, p < 0.001) and a higher likelihood of adherence (HR = 2.40, 95% CI 1.58-3.64, p < 0.001). After matching, the B/F/TAF group exhibited lower 12-month consumption of non-HIV medications, fewer non-HIV hospitalizations, and reduced total healthcare costs, particularly for non-HIV drug prescriptions compared to other ART users. CONCLUSIONS:Overall, B/F/TAF was associated with better treatment continuity and meaningful cost savings.

BACKGROUND:Although long-acting cabotegravir plus rilpivirine (CAB + RPV long-acting [LA]) has demonstrated high efficacy in clinical trials, real-world data on archived resistance and HIV-1 reservoir dynamics remain limited. METHODS:Archived resistance profile and total HIV-1 DNA were assessed at baseline (BL) and over 52 weeks in 36 virologically suppressed participants who switched to CAB + RPV LA, followed at the Polyclinic of Foggia, Italy. Total HIV-1 DNA in whole blood was quantified by real-time PCR. Resistance and APOBEC-context mutations were assessed through the Stanford HIVdb algorithm. RESULTS:At BL, participants had a median body mass index of 26.1 kg/m² and prior virological suppression (VS) of 8.5 y; none of them harboured A6 subtype. Thirty-four participants (94.4%) maintained VS after 52 weeks on CAB + RPV LA, with a stable total HIV-1 DNA (3.5 at BL vs. 3.7 log10 copies/10⁶ CD4 at week 52, P = 0.324). BL prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) and integrase strand transfer inhibitor (INSTI) major mutations was 18.2% and 6.5%, respectively. NNRTI prevalence remained constant, while no major INSTI mutations were found at week 52. Excluding APOBEC-context mutations, NNRTI resistance prevalence was about 9% at both time points, while no INSTI major mutations were found. In the two participants who failed CAB + RPV LA, NNRTI resistance was detected at failure; they subsequently regained VS after treatment modification. CONCLUSIONS:In this real-world study, stable HIV-1 DNA over 52 weeks of CAB + RPV LA treatment was observed. A substantial proportion of participants harboured NNRTI or INSTI major mutations, mostly APOBEC-context, without conferring true resistance. These findings emphasize the importance of a careful interpretation of proviral resistance.

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.

Dermatofibrosarcoma protuberans (DFSP) is a rare tumor presenting as a slow-growing, plaque-like or multinodular, brownish lesion on the trunk in adult patients. Diagnosis is established by histological examination and surgical excision is the primary treatment. Typically, DFSP has an indolent course and local spread. In the present work, we describe the clinical-histologic features, surgical treatment and follow-up of a case of DFSP in a patient living with HIV infection (PLWH). A 40-year-old man was referred to us with confluent lesions on the left shoulder, present for about 3 years. His medical history was positive for HIV-1 infection, for which he was taking antiretroviral therapy. Microscopic examination showed dermal and hypodermic proliferation of spindle cells in a storiform pattern, confirming the clinical diagnosis of DFSP. A wide excision was performed with 3 cm clinically healthy tissue margins, and the defect was repaired using an artificial bilaminar dermal matrix. The histological examination revealed tumor-free margins, and a split-thickness skin graft was harvested from the same arm. After 10 months, the patient was free from the disease. As observed with other skin cancers, DFSP may have a higher incidence and greater aggressiveness in immunosuppressed than in immunocompetent patients. DFSP has been reported only twice in PLWH. Our case constitutes a third report, adding to the evidence that there may be an over-representation of this cancer in immunosuppressed individuals.

Background: Advanced HIV disease (AHD) remains highly prevalent and is associated with increased morbidity and mortality. Missed opportunities for early diagnosis continue to represent a major public health challenge. Methods: We conducted a multicenter retrospective cohort study including antiretroviral-naive people with HIV (PWH) presenting with AHD (CD4 < 200 cells/µL and/or AIDS) diagnosed between 1 January 2019 and 31 December 2024 in four Italian infectious diseases units. Demographic, clinical and viro-immunological data were collected at baseline and during follow up. Information on healthcare contacts, HIV-related symptoms, and prior HIV testing in the two years preceding diagnosis was obtained through structured interviews. Results: Among 658 newly diagnosed participants with HIV, 224 (34%) presented with AHD, of whom 54% presented with AIDS. Most participants (86.2%) had never undergone HIV testing before diagnosis. In the year preceding diagnosis 29.3% accessed healthcare services for symptoms compatible with HIV infection without being tested for HIV. At one year, 84.2% achieved virological suppression, with a median CD4 count of 260 cells/µL. Overall loss to follow-up was 27.2%. Five-year survival was significantly higher in non-AIDS presenters compared with AIDS presenters (100% vs. 85%, p = 0.005). Conclusions: Missed diagnostic opportunities remain frequent among PWH presenting with AHD, despite prior healthcare contacts. Wider implementation of indicator condition-guided HIV testing is urgently needed to reduce late diagnosis and improve long-term outcomes.

BACKGROUND:Neglected Tropical Diseases (NTDs) affect nearly two billion people worldwide, yet preparedness to diagnose and manage them remains limited in high-income countries (HICs), where shifting epidemiology driven by climate changes, migration, mobility, international food and animal trade and global interconnection requires broader clinical competencies. Evidence on NTD-related knowledge among medical trainees in Europe is scarce. This study aimed to develop, validate, and field-test a comprehensive instrument assessing knowledge, attitudes, and practices (KAP) regarding NTDs among Italian medical students, recent graduates, and residents. METHODS:A structured questionnaire was developed using a multi-step approach informed by World Health Organization (WHO) Neglected Tropical Diseases priorities and a targeted literature review. Content validity was assessed through a two-round Delphi process with a multidisciplinary national expert panel (Round 1: n = 36; Round 2: n = 34), followed by external expert evaluation (n = 17). Quantitative content validation included Item- and Scale-Level Content Validity Indices (I-CVI, S-CVI/Ave) and interquartile ranges (IQR) to assess expert consensus. Reliability and psychometric properties were evaluated in a national sample of Italian medical trainees (n = 96), including internal consistency (Cronbach's α; KR-20), test-retest reliability (ICC; Cohen's κ), and item performance analyses. RESULTS:Across Delphi rounds, 91-98% of items reached consensus (IQR ≤ 1), and overall content validity was excellent (S-CVI/Ave 0.96-0.98). Reliability metrics confirmed strong internal consistency (α = 0.863; KR-20 = 0.82) and good temporal stability (ICC = 0.89; κ = 0.72-0.84). Known-groups validity was demonstrated by significantly higher knowledge scores among residents compared with medical students (p = 0.014). CONCLUSIONS:This study provides the first Delphi-validated national instrument assessing NTD-related knowledge among Italian medical trainees. The tool can offer a foundation for evaluating curricula and informing educational reform, supporting the integration of NTD-related competencies in European medical education in response to evolving global health challenges.

COVID-19 is still a potentially serious infection in immunocompromised individuals, with a significant risk of respiratory failure; nevertheless, the optimal treatment strategy is uncertain. Herein, the impact of combination therapy versus monotherapy on risk of respiratory failure was evaluated. This study is a pragmatic target trial emulation performed on observational data collected between 01/01/2022 and 31/03/2024 in 4 tertiary-care hospitals. Patients: immunocompromised patients with mild/moderate COVID-19. Intervention: (arm A) monotherapy with antivirals (DAAs) or monoclonal antibodies (MoAbs) versus (arm B) combination therapy of MoAbs plus DAAs. Primary endpoint: COVID-19-related acute respiratory failure on day 28 post-randomization. Secondary aims: adverse events to therapy, 90-day mortality, 90-day COVID-19 recurrence/complications, and duration of viral shedding. Overall, 1,035 subjects were screened, and 303 immunocompromised patients were included; main immunodeficiencies were hematologic cancer (71

OBJECTIVES:Undernutrition remains one of the most powerful yet neglected determinants of tuberculosis (TB) incidence and progression. Although its impact on TB outcomes has been extensively described in low-income countries, limited evidence is available from high-income settings. This study aimed to assess the association between body mass index (BMI) strata at treatment initiation and TB-related outcomes in a large multicentre cohort from Italy. METHODS:We conducted a retrospective, multicentre observational study including all adults diagnosed with TB between January 2021 and August 2025 in 16 Infectious and Tropical Diseases Units across seven Italian regions. Patients were stratified by BMI at treatment initiation (<16, 16-16.99, 17-18.49, 18.5-24.99, and ≥25 kg/m2). Outcomes included time to sputum conversion, length of hospital stay, occurrence and severity of adverse events, incomplete treatment (including failure, death, and loss to follow-up), and loss to follow-up. Multilevel regression models adjusting for study centre and relevant confounders were used to assess associations between BMI strata and each outcome. RESULTS:A total of 709 people with TB were included (median age, 38 years [interquartile range 28-53]; 488/709, 75.5% male). Overall, 299 of 709 (42%) were underweight (BMI <18.5 kg/m2). Compared with people with TB with normal BMI (18.5-24.99 kg/m2), those with severe undernutrition (BMI <16 kg/m2) showed higher rates of adverse events (54/74 [73.0%] vs. 101/410 [24.6%]; adjusted OR [aOR] 12.17, 95% CI 6.41-23.08), incomplete treatment (53/74 [71.6%] vs. 87/410 [21.2%]; aOR 18.28, 95% CI 6.70-49.80), and loss to follow-up (41/74 [55.4%] vs. 81/410 [19.7%]; aOR 5.99, 95% CI 2.58-13.90). Median hospital stay was also longer in this group (50 days [interquartile range 24-66] vs. 30 days [interquartile range 18-60]), corresponding to a 23% adjusted increase. Weight gain during the first 6 months of treatment was not significantly associated with major outcomes. CONCLUSIONS:Severe underweight at treatment initiation is a major independent predictor of poor outcomes in TB. These findings highlight the need for systematic nutritional assessment and targeted interventions within TB programmes, even in high-income, low-incidence settings.

Background:The risk of developing low-level viral rebound (LLVR) after achieving human immunodeficiency virus HIV-1 (HIV) RNA suppression with 2-drug regimens (2DR) compared to 3-drug regimens (3DR) remains uncertain. Methods:We conducted a matched 1:3 case-control study nested within the ICONA cohort including persons with HIV (PWH) who achieved virological suppression (≥2 consecutive HIV-RNA ≤50 copies/mL over 6 months) after 11 November 2014 (baseline [BL]). Cases were defined as PWH experiencing a single HIV-RNA of 51-199 copies/mL after BL (index date); controls were defined as those who maintained HIV-RNA ≤50 copies/mL up to the index date and were matched for history of care gaps and number of drugs failed. The cumulative incidence of LLVR after virological suppression was estimated using Kaplan-Meier methods, and conditional logistic regression models were used to evaluate the association between the current antiretroviral therapy regimen (2DR [dolutegravir/lamivudine, dolutegravir/rilpivirine, dolutegravir/doravirine, or cabotegravir/rilpivirine] vs 3DR [dolutegravir, bictegravir, rilpivirine, doravirine, boosted darunavir, or boosted atazanavir-based with a backbone of tenofovir and lamivudine or emtricitabine]) and LLVR risk. In sensitivity analyses cases were defined as PWH experiencing 2 consecutive HIV-RNA of 51-199 copies/mL. Results:Among 1033 PWH (261 cases, 772 matched controls), 21% were female, median age was 43 (interquartile range [IQR], 34-51) years, and BL CD4 count was 601 (IQR, 379-826) cells/μL; 2DR use was 25% in cases versus 29% in controls (P = .23). Two years after viral suppression, cumulative LLVR incidence was 2.7% (95% CI, 2.3%-3.1%) when considering single LLVR events and 1.8% (95% CI, 1.4%-2.1%) when limited to 2 consecutive values. After adjusting for confounding, evidence for an association with current regimen was inconclusive (adjusted odds ratio, 0.86 [95% CI, .57-1.29]). Conclusions:Despite the wide range of plausibility, we can exclude a risk of LLVR higher than 29% when using 2DR versus 3DR regimens.

Sex disparities in tuberculosis (TB) outcomes are not well characterized, especially in high-income countries where social vulnerability and migration influence access to care. Although men globally experience a higher TB burden, the interaction between sex, migration, and social determinants is complex and extends beyond biological factors. This study evaluated sex differences in clinical and programmatic TB outcomes in a high-income European country with a significant substantial migrant population. A retrospective multicentre cohort study was conducted across 16 Infectious Diseases Units in seven Italian regions from (January 2021 to September 2025). Outcomes included time to sputum conversion (in pulmonary TB), length of hospital stay (LOS), adverse events (AEs) and their severity, incomplete treatment (defined as failure, death, or loss to follow-up), and loss to follow-up (LTFU). Mixed-effects models were applied using two prespecified adjustment sets: sex, centre, and core confounders (Model A); and sex, centre, and clinically relevant baseline imbalances (Model B). Sub-analyses examined the impact of migration status. Of 982 TB patients, 229 (23.3

OBJECTIVES:This analysis aimed to evaluate the rate of failure of first-line lamivudine/dolutegravir in a real-world setting and assess the effectiveness among people with HIV (PWH) at higher risk of suboptimal response. METHODS:The study included PWH from the ICONA cohort who started first-line lamivudine/dolutegravir between 2016 and 2024. The primary endpoint was time to treatment failure (TF), defined as virological failure (VF, two consecutive HIV-RNA of >50 copies/mL >6 months after treatment initiation) or discontinuation due to toxicity/lack virological control/non-adherence or death for any cause. Secondary endpoints were time to treatment discontinuation for any reason (TD) and pure VF. Main exposures of interest were baseline CD4 and HIV-RNA, age, sex at birth and nation of birth. Standard survival analysis and Cox regression models were used. RESULTS:Among 446 participants, after a median follow-up of 22 months, 4.3% (n = 19) experienced TF, the 3 year cumulative probability was 5.8% (95% CI: 2.9%-8.7%). Baseline CD4 count was associated with a 3-fold higher risk of TF, which decreased after adjustments. Higher viral loads (>100 000 copies/mL), age >50 years and foreign-born status were also associated with an increased risk of TF. No differences in TF according to sex at birth were found. By 3 years the probabilities of TD and VF were 13.4% (95% CI: 9.1%-17.6%) and 2.3% (95% CI: 0.19%-4.4%), respectively. CONCLUSIONS:In our real-world setting, the TF probability for first-line lamivudine/dolutegravir was below 6% at 3 years, lower than in randomized trials. Our data suggest that, as shown with other regimens, PWH starting lamivudine/dolutegravir with CD4 count of ≤200 cells/mm3, HIV-RNA of >100 000 copies/mL, older age or foreign-born status may be at higher risk of TF, though larger studies are needed to qualify the magnitude of the effect.

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.

BACKGROUND:Tuberculosis (TB) remains a Global Health challenge, with diagnostic delays contributing significantly to its spread. This study investigates the differences in diagnostic delays between native and migrant TB patients in Italy, examining patient-related diagnostic delay (PDD), health system-related diagnostic delay (HDD), and total diagnostic delay (TDD). METHODS:We conducted a retrospective, multicenter, cross-sectional study of TB cases in 10 Italian hospitals from 2018 to 2023. We compared PDD, HDD, and TDD between native and migrant populations. Socio-demographic data and clinical histories were analyzed to identify factors contributing to diagnostic delays. RESULTS:We included 669 TB patients (390 migrants and 279 natives). Migrants experienced significantly longer PDD (median 90 vs 10 days, P < 0.0001) but shorter HDD (median 5 vs 40 days, P < 0.0001) compared to natives, resulting in a longer TDD (median 96 vs 65 days, P < 0.0001). Furthermore, migrants had higher Timika scores, longer sputum conversion times, and were more frequently lost to follow-up. CONCLUSION:Migrants face longer PDD, emphasizing substantial barriers to healthcare access. Natives experience longer HDD, reflecting neglect of TB in low-endemic regions. Future research should focus on the impact of social determinants and training for healthcare providers on TB diagnosis and develop strategies to reduce diagnostic delays.

Objectives: This study investigated the role of low-frequency integrase strand transfer inhibitor (INSTI) resistance mutations, detectable by next-generation sequencing (NGS), at predicting virological rebound (VR) among people with HIV (PWH) starting second-generation INSTI-based first-line regimens. Methods: This case-control study compared PWH (retrieved from the ICONA cohort; www.icona.org) who experienced VR (cases) with those who maintained virological control (controls) under first-line regimens based on dolutegravir or bictegravir. NGS data obtained through the Illumina platform were interpreted using the HIVdb algorithm version 9.7. Major (MRM), accessory (ARM), and other (ORM) INSTI resistance mutations were analysed at 5%, 10%, and 20% NGS cut-offs, respectively. Conditional logistic regression was used to evaluate the association between INSTI resistance and risk of VR. Results: Among 266 PWH (90 cases, 176 controls), cases experienced VR with a median (interquartile range) viremia of 317 (93–6060) copies/mL after 15 (8–28) months from antiretroviral therapy start. The prevalence of MRM was low (NGS cut-off 5%, 10%, 20%: 1.9%, 0.8%, 0.4%, respectively), while it was moderate for ARM (7.5%, 7.1%, 6.4%) and high for ORM (50.0%, 44.7%, 42.1%). There was no evidence of a difference in prevalence of ≥1 MRM, ARM, or ORM between cases and controls. At 5% NGS cut-off, the prevalence of ≥2 ORM was higher in cases compared with controls. After adjusting for confounders, including HIV-1 subtype, ≥2 ORM detected as minority variants remained associated with VR risk. Conclusion: Our findings suggest that combinations of low-frequency ORM may increase the risk of VR in individuals starting dolutegravir or bictegravir-based regimens. Further studies are needed to better understand these findings.

OBJECTIVES:Tuberculosis (TB) continues to pose challenges in high-income countries, among migrant and socioeconomically vulnerable populations. Treatment discontinuity and loss to follow up (LTFU) remain critical barriers to TB control. This study evaluated the impact of three organizational models of TB care on clinical and programmatic outcomes in Italy. METHODS:We conducted a multicentre study including all TB patients diagnosed between 2021 and 2024 in 11 hospitals in five regions. Centres were categorized into three care models: (i) TB team (structured care with trained staff, dedicated outpatient clinics, and proactive follow-up); (ii) hybrid centre (HC); and (iii) standard-of-care (SOC). Primary outcomes included hospital length of stay, incidence and severity of adverse events, treatment completion, and LTFU. Mixed-effect regression models adjusted for confounders. RESULTS:Of 717 pansusceptible and monoresistant TB patients, 375 (52.3%) were treated in TB team centres, 175 (24.4%) in HC, and 167 (23.3%) in SOC centres. Treatment completion was higher in TB team (327/375, 87.2%) vs. HC (116/162, 71.6%) and SOC centres (89/158, 56.3%) (p < 0.0001), whereas LTFU was lowest in TB team (35/375, 9.3%) vs. HC (44/162 27.2%) and SOC (63/158, 39.9%) (p < 0.0001). Hospital stay was shorter in the TB team (median 26 days, interquartile range (IQR), 15-55) and HC (35 days, IQR, 22-62) compared with SOC (50 days, IQR, 22-82) (p < 0.0001). The occurrence of adverse events was similar (p 0.54), with lower severity in the TB team and HC. Adjusted analyses confirmed lower risk of incomplete treatment (OR, 0.10; 95% CI, 0.03-0.30), LTFU (OR, 0.09; 95% CI, 0.04-0.23), and severe adverse events (OR, 0.40; 95% CI, 0.17-0.95) in the TB team vs. SOC. DISCUSSION:The TB-dedicated care model was associated with improved outcomes, fewer severe adverse events, higher treatment completion rates, and lower LTFU. Although hybrid models conferred intermediate benefit, implementation of TB care ensured consistent gains. These findings support scaling up TB team-based models to strengthen TB control and align with elimination targets.

Background Major adverse cardiovascular events (MACEs) may contribute to the high morbidity in people with four-class drug-resistant HIV (4DR-PWH). Objectives To explore the probability of MACEs in 4DR-PWH compared with non-4DR controls. Methods This was a retrospective, propensity score-matched cohort study on 4DR-PWH (cases) and non-4DR-PWH (controls), on ART, without previous MACEs. Controls were matched with cases in a 4:1 ratio for age, sex-assigned-at-birth and ART duration. Incidence rates (IRs) and incidence rate ratio (IRR) of MACEs with 95% CIs were modelled by Poisson regression. Cumulative probabilities of the first incident MACE were estimated by Kaplan-Meier curves. A multivariable stepwise Cox proportional hazards model estimated predictors of incident MACEs among covariates with univariable P < 0.100. Results Overall, 223 4DR-PWH and 797 non-4DR-PWH were evaluated. During a median (IQR) follow-up of 8.2 (5.4-11.1) years [1833 person-years of follow-up (PY)], 23/223 (10.3%) 4DR-PWH developed 29 MACEs, IR = 1.6 (95% CI = 1.1-2.3)/100 PY. During a median follow-up of 8.4 (5.2-11.0) years (6450 PY), 42/797 (5.3%) non-4DR controls had 45 MACEs, IR = 0.7 (95% CI = 0.5-0.9)/100 PY, IRR (4DR/non-4DR) = 2.3 (95% CI = 1.4-3.6). The cumulative probabilities of the first MACE were more than doubled in 4DR-PWH (P = 0.006). At multivariable analysis, an increased risk of MACEs was associated with 4DR status [adjusted hazard ratio (aHR) = 1.9; 95% CI = 1.0-3.4], after adjusting for age, sex-assigned-at-birth, HIV load, CD4(+) nadir, total cholesterol, HDL cholesterol, diabetes mellitus, statin use and baseline HCV serostatus. Conclusions In PWH, MDR is significantly associated with a higher risk of cardiovascular events. Prompt implementation of prevention strategies is mandatory in this fragile population.