Risk of Developing Low-Level Viral Rebound Among People With HIV Receiving 2- or 3-Drug Regimens: A Case-Control Study Nested in the ICONA Cohort Alessandra Vergori, Adriana Cervo, Ashley Roen, Roberta Gagliardini, Tommaso Clemente, et al. Open Forum Infectious Diseases, 2026 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.
‘Leaving no stones unturned’: up to 10 years results on the effectiveness, tolerability and metabolic safety of dolutegravir+lamivudine (DTG+3TC) as a switch regimen in the ODOACRE cohort Arturo Ciccullo, Gianmaria Baldin, Adriana Cervo, Letizia Oreni, Maria Mazzitelli, et al. Journal of Antimicrobial Chemotherapy, 2026 Background Dolutegravir plus lamivudine (DTG+3TC) is widely used as a two-drug switch regimen for virologically suppressed PWH. We report long-term real-world data on effectiveness, tolerability, immunological recovery and metabolic/cardiovascular outcomes in a large, multicentre Italian cohort. Methods We performed a retrospective observational analysis of participants in the ODOACRE cohort who switched to DTG+3TC between January 2015 and January 2025 across eight Italian centres. Inclusion criteria were age ≥18, HIV-RNA <50 copies/mL for ≥6 months at switch, HBsAg negative. Primary outcomes were time to virological failure (VF) and time to treatment discontinuation (TD) for any cause. Kaplan–Meier survival analysis and Cox regression models were used to evaluate predictors. Changes in metabolic and immunological markers were assessed using linear mixed models and linear regression. Results A total of 2535 participants were included. Estimated probabilities of maintaining virological suppression were 99.5% at 48 weeks, 96.1% at 240 weeks and 90.4% at 480 weeks. In multivariate analysis, longer time since HIV diagnosis (per year aHR 1.038) and zenith HIV-RNA >500 000 copies/mL (aHR 2.205) predicted VF, whereas longer prior virological suppression was protective (per year aHR 0.869). During 9721.6 PYFU we observed 362 TDs (3.72 per 100 PYFU), with probabilities of regimen maintenance of 94.4%, 83.5% and 78.7% at weeks 48, 240 and 480, respectively. Conclusions In our real-world cohort with extended follow-up, DTG+3TC as a switch regimen was associated with durable virological suppression and favourable tolerability. Metabolic findings should be considered descriptive and exploratory, within the limits of an observational, uncontrolled study.
Impact of Vancomycin-Resistant Enterococci (VRE)–Active Perioperative Prophylaxis in Liver Transplant Patients Colonized by VRE Giulia Jole Burastero, Emmanuel Q Wey, Veronica Guidetti, Samuele Cantergiani, Valentina Menozzi, et al. Clinical Infectious Diseases, 2026 Background Data regarding the effectiveness of vancomycin-resistant Enterococci (VRE)–active prophylaxis for preventing early post–liver transplantation (LT) VRE infections in VRE-colonized patients are scarce. Methods 131 pre-LT VRE-colonized patients who underwent LT were enrolled in a retrospective, observational, multicenter study. The incidence of early-onset VRE infections was compared between patients who received active prophylaxis for VRE and those who did not. Results Sixty-nine (52.7%) and 62 (47.3%) patients were enrolled in the VRE-active and non–VRE-active prophylaxis group. Tigecycline was the most common drug prescribed as VRE-active for prophylaxis (55/69; 79.7%). There was no significant difference in the number of patients who developed early-onset VRE infections in the VRE-active versus non–VRE-active groups at 7 (0 [0.0%] vs 2 [3.2%]; P = .222), 14 (4 [5.7%] vs 4 [6.4%]; P = 1.000), and 30 (6 [8.7%] vs 8 [12.9%]; P = .621) days post-LT, respectively. Risk of early-onset VRE infection within 30 days was not lower in the VRE-active group (log-rank P = .16 with Kaplan-Meier analysis; odds ratio [OR]: .643; 95% CI: .210–1.969; P = .439 with univariate analysis). Conversely, early infections caused by any pathogen were significantly lower in the VRE-active prophylaxis group compared with the control group (11 [15.9%] vs 20 [32.2%]; P = .047). Tigecycline prophylaxis was associated with a lower risk of early-onset infections with multivariate analysis (OR: .106; 95% CI: .015–.745; P = .024) and after adjusting for propensity score (adjusted OR: .146; 95% CI: .031–.708; P = .017). Conclusions VRE-active prophylaxis at LT did not reduce the incidence of early post-LT VRE infections and should not be recommended.
All-Cause Mortality in People with Four-Class Drug-Resistant HIV: A Matched Cohort Analysis with Data from the PRESTIGIO Registry Andrea Giacomelli, Nicolò Capra, Riccardo Lolatto, Roberta Gagliardini, Tommaso Clemente, et al. Clinical Infectious Diseases, 2025 People with human immunodeficiency virus (HIV) (PWH) with 4-drug class resistance (4DR) had a higher risk of death than non-4DR PWH, primarily due to lower CD4 cell counts. The priority for this vulnerable population is achieving virological control to enable immune recovery.
Evaluation of HIV-1 DNA resistance evolution in highly treatment-experienced and multi-resistant individuals under suppressive antiretroviral therapy: a longitudinal study from the PRESTIGIO Registry D Armenia, G Marchegiani, V Spagnuolo, M C Bellocchi, L Galli, et al. Journal of Antimicrobial Chemotherapy, 2025 Background This study aimed to clarify whether resistance detected in HIV-1 DNA might evolve in virologically suppressed highly treatment-experienced (HTE) individuals with multidrug resistance (MDR). Methods Twenty-three virologically suppressed HTE MDR individuals from the PRESTIGIO Registry with two longitudinal samples available under virological suppression at two different time points (T0−T1) were analysed. HIV-1 DNA levels were quantified using droplet digital PCR, and resistance was assessed through next-generation sequencing (NGS) set at 5%. Mutational load was also evaluated. Results At T0, individuals had been virologically suppressed for a median time of 3 years (IQR 3–5) under a salvage regimen, mostly containing dolutegravir (95.7%) and/or darunavir (69.6%). The median HIV-1 DNA level was 2588 copies/106 CD4+ cells at T0 and remained stable at T1 (2322 copies/106 CD4+ cells; P = 0.831). Individuals with at least ≥3-class resistance in HIV-1 DNA were 20 (87.0%) at T0 and 18 (78.2%) at T1 (P = 0.607). In those receiving NNRTI-sparing treatment (52.2%), the number of NNRTI major resistance mutation (MRM) significantly decreased over time (T0, 2 [1–3]; T1, 0 [0–1]; P = 0.027). No significant temporal differences in the number of PI, NRTI and integrase strand transfer inhibitor (INSTI) MRM were found. Specific MRM, such as M184V, decreased over time, particularly in individuals who were receiving a 3TC-/FTC-sparing salvage regimen or with a T0 mutational load of &lt;1000 copies/106 CD4+ cells. Conclusions Over a year, HIV-1 DNA MRM generally remained unchanged in suppressed HTE MDR people with HIV (PWH) except for a significant decline in M184V and a reduction of NNRTI resistance in the absence of NNRTI pressure.
Proactive antimicrobial stewardship with real-time microbiological alerts improves management of bloodstream infections Arianna Di Marcello, Antonella Santoro, Vera Todisco, Erica Franceschini, Gabriella Orlando, et al. Jac Antimicrobial Resistance, 2025 Introduction This study aims to assess the impact of proactive Infectious Disease Specialist (IDS) interventions, in addition to standard antimicrobial stewardship (AMS) practices, triggered by real-time microbiological alerts, on improving the appropriateness and timeliness of antimicrobial prescriptions in hospitalized patients with bloodstream infections (BSIs). Methods We conducted a prospective, single-center, pre-post interventional study at the University Hospital of Modena, Italy. Adult inpatients with monomicrobial BSIs between June 2022 and March 2023 were included. During the intervention phase (November 2022–March 2023), real-time microbiological alerts were automatically delivered to IDS consultants, who proactively reviewed therapy. Primary outcomes included the time to effective therapy (TTE) and the time to appropriate therapy (TTA). Secondary outcomes encompassed the duration of antimicrobial therapy, 14 and 30-day mortality from BSI, and hospital length of stay. Results A total of 446 BSI episodes were analyzed (211 pre-intervention, 235 post-intervention). Post-intervention, the rate of appropriate therapy significantly increased (97.4% versus 76.2%, P &lt; 0.001), and TTE was significantly shorter (0.63 versus 0.87 days, P = 0.022). No statistically significant reduction in TTA was observed (1.97 versus 2.37 days, P = 0.081). Early IDS intervention (&lt;48 h) was associated with the shortest TTE and TTA. No significant differences were observed in mortality or hospital stay. Kaplan–Meier analysis showed a higher probability of receiving effective and appropriate therapy earlier in the post-intervention phase (log-rank test P = 0.014; 0.072, respectively). Subgroup analysis showed TTE improvements across MDR pathogens. Conclusions A proactive intervention of IDS, based on automatic microbiological alert, in addition to routine AMS activities, is significantly associated with improved prescription appropriateness, reducing TTE.
Persistence of CXCR4-tropic virus in people living with four-class drug-resistant HIV and its clinical impact in the modern antiretroviral era Rebecka Papaioannu Borjesson, Sara Diotallevi, Riccardo Lolatto, Giovanni Cenderello, Laura Comi, et al. Journal of Antimicrobial Chemotherapy, 2025 Background CXCR4-tropic HIV seems to be associated with more clinical events than CCR5-tropic virus. Objectives This study aims to describe the effect of the persistence of CXCR4-tropic virus on the occurrence of clinical events in people with four-class drug-resistant HIV. Methods This is a retrospective study on people with four-class drug-resistant HIV from the PRESTIGIO Registry, with at least two HIV-tropism determinations during follow-up. Follow-up accrued from the date of the first four-class drug resistance evidence (baseline) until death, loss to follow-up or freezing date (31 December 2023). Univariable Poisson regression was used to estimate and compare incidence rates of clinical events. Predictors of clinical events were assessed by multivariable Poisson regression. Results A total of 144 people with four-class drug-resistant HIV [47 (33%) with persistent CXCR4-tropism, 39 (27%) with persistent CCR5-tropism and 58 (40%) with a tropism switch during follow-up] were included with a median follow-up of 7.80 years (IQR = 5.80–10.6). Overall, 117 (81.3%) 4DR-PLWH experienced at least one clinical event during follow-up [incidence rate = 32.5 (95% CI = 29.3–35.9)]. The persistence of CXCR4-tropic virus was associated with an increased risk of HIV-related events among people living with four-class drug-resistant HIV, even in modern ART era. After adjusting for age, sex at birth and CD4+/CD8+ at baseline, standardized viremia copy-years [adjusted-incidence rate ratio = 1.66 (95% CI = 1.24–2.26), P &lt; 0.001] and persistent CXCR4-tropism [adjusted-incidence rate ratio: 2.01 (95% CI = 1.04–3.91), P = 0.037] were associated with the occurrence of HIV-related events. Conclusions Our findings confirm CXCR4-tropism as a marker of HIV progression also in the four-class drug-resistant population, suggesting the need of further prioritization of viro-immunological control and studies of pathogenic mechanisms in presence of CXCR4-tropic multidrug-resistant viral strains.