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Objective: To assess the correlation of serum protein biomarkers with disease activity across different domains of psoriatic arthritis (PsA). Material and methods: A cross-sectional cohort of 45 adult patients with PsA fulfilling the classification for psoriatic arthritis (CASPAR) criteria was recruited from University of California San Diego (UCSD) Arthritis Clinics. Clinical data and serum samples were collected and serum was analyzed for protein biomarkers hypothesized to be relevant to disease activity in PsA. Correlations were evaluated for clinical disease activity measures across disease domains. Results: Biomarkers with the highest correlation to the composite indices and disease domains were SAA, IL-6, YKL-40, and ICAM-1. In addition, several biomarkers were moderately correlated with individual composite indices and/or disease domains. Low or no correlation was observed with some biomarkers, e.g. MMP-3, MMP-1, EGF, VEGF, and IL-6R. In contrast, the correlation of all biomarkers with certain disease domains was low; specifically, pain, percent body surface area of psoriasis, and patient global assessment. The multi-biomarker disease activity score (MBDA) developed for rheumatoid arthritis (RA) showed high correlations with most composite indices and some disease domains in PsA. Conclusions: These data suggest biomarker analysis can reflect disease activity across disease domains in PsA. Certain domains would likely benefit from the evaluation of additional biomarkers. [ABSTRACT FROM AUTHOR]

In this paper, we study some relevant properties of generic quantum Markov semigroups, in particular related to their asymptotic behavior. We can describe the structure of the set of fixed points and of the invariant states in terms of the Hamiltonian's spectrum and of the communication classes of the classical Markov process associated with the diagonal part of the semigroup. Moreover we study the decoherence-free algebra and we complete the characterization of environmental decoherence for a generic quantum Markov semigroup. [ABSTRACT FROM AUTHOR]

We consider the problem of expected power utility maximization from terminal wealth in diffusion market models under partial information. After obtaining novel neat expressions for the value-process and for the optimal strategy, the issue of information sufficiency is addressed. In particular, necessary and sufficient conditions that guarantee that the partial information optimal strategy is still optimal when having access to all market information, are provided. [ABSTRACT FROM PUBLISHER]

We study ergodicity and decoherence for generic quantum Markov semigroups: in particular, we highlight the strong relationships among these properties, the convergence in law of the classical Markov process associated with the diagonal part of the semigroup, and the structure of its communication classes. [ABSTRACT FROM AUTHOR]

1. The pharmacokinetics and metabolism of primidone at steady-state were studied in 10 elderly patients aged 70-81 years and eight control subjects aged 18-26 years. 2. Primidone half-lives and clearance values (mean +/− s.d.) were similar in the elderly and in the young (12.1 +/− 4.6 vs 14.7 +/− 3.5 h and 34.8 +/− 9.0 vs 33.2 +/− 7.2 ml h-1 kg-1 respectively. 3. The serum concentrations of the metabolites phenylethylmalonamide (PEMA) and phenobarbitone relative to those of parent drug were higher in the elderly than in the young, the difference being significant (P less than 0.01) in the case of PEMA. 4. The renal clearances of primidone, phenobarbitone and PEMA were moderately decreased in the elderly but this reduction was statistically significant only for PEMA. Elderly patients excreted a reduced proportion of unchanged primidone and an increased proportion of PEMA in urine. 5. Ageing is associated with a greater accumulation of PEMA, which is unlikely to have a major clinical significance. [ABSTRACT FROM AUTHOR]

Feather analysis is an ethical and effective method for assessing the exposure of wild birds to environmental contamination due to trace elements and organic pollutants. We used feather to monitor the exposure to three toxic and non-essential metals (Hg, Cd, and Pb) and rare earth elements (REEs) of Kentish plover (Charadrius alexandrinus) breeding in different coastal areas (Veneto, Emilia-Romagna, Marche, Abruzzo, and Apulia) along the Italian coast of the Adriatic Sea. Feathers (n = 113) were collected from April to June. Feather concentrations evidenced a significant exposure to Hg (13.05 ± 1.71 mg kg -1 dw) and REEs (447.3 ± 52.8 ng g -1 dw) in the Kentish plover breeding in Veneto (n = 21) compared to the other coastal areas, with several individuals showing Hg concentrations above the adverse effect (5 mg kg -1 dw) and high-risk (9.14 mg kg -1 dw) thresholds reported for birds. Higher REE concentrations compared to Marche (n = 29), Abruzzo (n = 11) and Apulia (n = 13) were also reported for birds breeding in Emilia-Romagna (474.9 ± 41.9 ng g -1 dw; n = 29). The exposure to Cd and Pb was low in all the coastal areas, and only a few samples (n = 6 and n = 4 for Cd and Pb, respectively) exceeded the adverse effect thresholds (0.1 and 4 mg kg -1 for Cd and Pb, respectively). A significant sex-related difference was observed for REE-concentrations, with females showing higher concentration than males. These data highlight the need to monitor the exposure of the Kentish plover to Hg and REEs, especially in the northern basin of the Adriatic Sea, since these elements might negatively affect species' reproductive success and threaten its conservation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gulf War Illness (GWI) is a chronic condition characterized by multisystem symptoms that still affect up to one-third of veterans who engaged in combat in the Gulf War three decades ago. The aetiology of GWI is mainly explained by exposure to multiple toxic agents, vaccines, and medications. As there is a significant overlap in symptoms between GWI and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), the objective of this study was to investigate a biomarker widely reported in Natural Killer (NK) cells from ME/CFS patients, the Transient Receptor Potential Melastatin 3 (TRPM3) ion channel. NK cells from 6 healthy controls (HC) and 6 GWI participants were isolated, and TRPM3 function was assessed through whole-cell patch-clamp. As demonstrated by prior studies, NK cells from HC expressed typical TRPM3 function after pharmacomodulation. In contrast, this pilot investigation demonstrates a dysfunctional TRPM3 in NK cells from GWI participants through application of a TRPM3 agonist and confirmed by a TRPM3 antagonist. There was a significant reduction in TRPM3 function from GWI than results measured in HC. This study provides an unprecedented research field to investigate the involvement of TRP ion channels in the pathomechanism and potential medical interventions to improve GWI quality of life., Competing Interests: The authors would like to declare the following patent applications associated with this research: SM-G and NE-F declare Patent Cooperation Treaty (PCT) patent application no. WO2016176726A1 and SM-G, EMS and NE-F declare PCT provisional application no. 2022902253. There are no additional patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Marshall-Gradisnik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The National Park of Gran Sasso and Monti della Laga (PNGSL) is located in Central Italy and covers an area of 143.311 ha across three administrative regions (Abruzzo, Marche, and Lazio). It is the protected area hosting the highest number of vascular plants in both Europe and the Mediterranean basin. The plan of the park recognizes the need to establish a list of plants of conservation interest to prioritize for protection. The aim of this study is to identify plants (vascular and bryophytes) for inclusion on a protection list, taking into account their phytogeographic importance as well as the threat of extinction, and subsequently propose an original categorization (protection classes) suggesting specific conservation actions and measures. We used original criteria to select plants of conservation interest among the 2678 plant taxa listed in the national park. We identified 564 vascular plant species and subspecies (including nine hybrids) and one bryophyte to be included in the proposed protection list. The case study of the PNGSL could be a model for other protected areas.

Neoantigen (neoAg)-based cancer vaccines expand preexisting antitumor immunity and elicit novel cancer-specific T cells. However, at odds with prophylactic vaccines, therapeutic antitumor immunity must be induced when the tumor is present and has already established an immunosuppressive environment capable of rapidly impairing the function of anticancer neoAg T cells, thereby leading to lack of efficacy. To overcome tumor-induced immunosuppression, we first vaccinated mice bearing immune checkpoint inhibitor (CPI)-resistant tumors with an adenovirus vector encoding a set of potent cancer-exogenous CD8 and CD4 T cell epitopes (Ad-CAP1), and then "taught" cancer cells to express the same epitopes by using a tumor-retargeted herpesvirus vector (THV-CAP1). Potent CD8 effector T lymphocytes were elicited by Ad-CAP1, and subsequent THV-CAP1 delivery led to a significant delay in tumor growth and even cure., Competing Interests: E. Scarselli, A.F., and A.N. are co-founders of Nouscom. F.T., G.L., G.R., S.A., G.C., E. Scareselli, and A.M.D. are employees of Nouscom. All of the other authors declare no competing interests., (© 2024 The Authors.)

An unbalanced diet increases the risk of developing a variety of chronic diseases and cancers, leading to higher morbidity and mortality rates worldwide. Low-grade systemic chronic inflammation mediated by the activation of the innate immune system is common to all these pathologies. Inflammation is a biological response of the body and a normal part of host defense to combat the effects of bacteria, viruses, toxins and macronutrients. However, when the innate immune system is constantly activated, it can promote the development of low-grade systemic chronic inflammation, which could play an important role in the development of chronic diseases and cancer. Since most chronic inflammatory diseases are associated with diet, a balanced healthy diet high in anti-inflammatory food components could prevent chronic diseases and cancer. The cells of the body's immune system produce chemokines and cytokines which can have pro-inflammatory and tumor-promoting as well as anti-inflammatory and tumor-fighting functions. A challenge in the future will be to assess whether polymorphisms in immune-related genes may play a role in promoting pro-inflammatory activity. Thanks to this duality, future research on immune regulation could focus on how innate immune cells can be modified to convert a pro-inflammatory and tumor-friendly microenvironment into an anti-inflammatory and anti-tumor one. This review describes inflammatory responses mediated by the innate immune system in various diseases such as hyperglycemia and/or hyperlipemia, obesity, type II diabetes, cardiovascular disease and cancer.

Different innate immune pathways converge to Stimulator of interferon genes (STING) and trigger type I interferon responses after recognition of abnormal nucleic acids in the cells. This non-redundant function renders STING a major player in immunosurveillance, and an emerging target for cancer and infectious diseases therapeutics. Beyond somatic mutations that often occur in cancer, the human gene encoding STING protein, TMEM173 (STING1), holds great genetic heterogeneity; R232, HAQ (R71H-G230A-R293Q) and H232 are the most common alleles. Although some of these alleles are likely to be hypomorphic, their function is still debated, due to the available functional assessments, which have been performed in biased biological systems. Here, by using genetic background-matched models, we report on the functional evaluation of R232, HAQ and H232 variants on STING function, and on how these genotypes affect the susceptibility to clinically relevant viruses, thus supporting a potential contributing cause to differences in inter-individual responses to infections. Our findings also demonstrate a novel toll-like receptor-independent role of STING in modulating monocytic cell function and differentiation into macrophages. We further supported the interplay of STING1 variants and human biology by demonstrating how monocytes bearing the H232 allele were impaired in M1/M2 differentiation, interferon response and antigen presentation. Finally, we assessed the response to PD-1 inhibitor in a small cohort of melanoma patients stratified according to STING genotype. Given the contribution of the STING protein in sensing DNA viruses, bacterial pathogens and misplaced cancer DNA, these data may support the development of novel therapeutic options for infectious diseases and cancer., (© 2023. The Author(s).)

The human carbonic anhydrase IX (CA IX) is a hypoxia-induced transmembrane protein belonging to the α-CA enzyme family. It has a crucial role in pH regulation in hypoxic cells and acts by buffering intracellular acidosis induced by hypoxia. Indeed, it is frequently expressed in cancer cells, where it contributes to tumor progression. CA IX is also able to localize in the nucleus, where it contributes to 47S rRNA precursor genes transcription; however, the mechanisms assisting its nuclear translocation still remain unclear. The aim of our study was to deepen the understanding of the mechanisms involved in CA IX subcellular distribution. To this purpose, we implemented a site-directed mutagenesis approach targeting the C-terminal domain of CA IX and evaluated the subcellular distribution of the wild-type and mutant proteins in the SH-SY5Y cell line. The mutant proteins showed impaired binding ability and altered subcellular distribution in both normoxic and hypoxic conditions. Our data suggest that CA IX nuclear translocation depends on its transit through the secretory and the endocytic pathways., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The recent pandemic years have prompted the scientific community to increasingly search for and adopt new and more efficient therapeutic and diagnostic approaches to deal with a new infection. In addition to the development of vaccines, which has played a leading role in fighting the pandemic, the development of monoclonal antibodies has also represented a valid approach in the prevention and treatment of many cases of CoronaVirus Disease 2019 (COVID-19). Recently, we reported the development of a human antibody, named D3, showing neutralizing activity against different SARS-CoV-2 variants, wild-type, UK, Delta and Gamma variants. Here, we have further characterized with different methods D3's ability to bind the Omicron-derived recombinant RBD by comparing it with the antibodies Cilgavimab and Tixagevimab, recently approved for prophylactic use of COVID-19. We demonstrate here that D3 binds to a distinct epitope from that recognized by Cilgavimab and shows a different binding kinetic behavior. Furthermore, we report that the ability of D3 to bind the recombinant Omicron RBD domain in vitro results in a good ability to also neutralize Omicron-pseudotyped virus infection in ACE2-expressing cell cultures. We point out here that D3 mAb maintains a good ability to recognize both the wild-type and Omicron Spike proteins, either when used as recombinant purified proteins or when expressed on pseudoviral particles despite the different variants, making it particularly useful both from a therapeutic and diagnostic point of view. On the basis of these results, we propose to exploit this mAb for combinatorial treatments with other neutralizing mAbs to increase their therapeutic efficacy and for diagnostic use to measure the viral load in biological samples in the current and future pandemic waves of coronaviruses.

Introduction: Virus vectored genetic vaccines (Vvgv) represent a promising approach for eliciting immune protection against infectious diseases and cancer. However, at variance with classical vaccines to date, no adjuvant has been combined with clinically approved genetic vaccines, possibly due to the detrimental effect of the adjuvant-induced innate response on the expression driven by the genetic vaccine vector. We reasoned that a potential novel approach to develop adjuvants for genetic vaccines would be to "synchronize" in time and space the activity of the adjuvant with that of the vaccine., Methods: To this aim, we generated an Adenovirus vector encoding a murine anti-CTLA-4 monoclonal antibody (Ad-9D9) as a genetic adjuvant for Adenovirus based vaccines., Results: The co-delivery of Ad-9D9 with an Adeno-based COVID-19 vaccine encoding the Spike protein resulted in stronger cellular and humoral immune responses. In contrast, only a modest adjuvant effect was achieved when combining the vaccine with the same anti-CTLA-4 in its proteinaceous form. Importantly, the administration of the adjuvant vector at different sites of the vaccine vector abrogates the immunostimulatory effect. We showed that the adjuvant activity of Ad-α-CTLA-4 is independent from the vaccine antigen as it improved the immune response and efficacy of an Adenovirus based polyepitope vaccine encoding tumor neoantigens., Discussion: Our study demonstrated that the combination of Adenovirus Encoded Adjuvant (AdEnA) with an Adeno-encoded antigen vaccine enhances immune responses to viral and tumor antigens, representing a potent approach to develop more effective genetic vaccines., Competing Interests: ESc and AN are founders of Nouscom. Authors AMD’A, LN, IG, LS, LI, FT, GC, SA, GR, AL, and GL were employed by Nouscom. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 D’Alise, Nocchi, Garzia, Seclì, Infante, Troise, Cotugno, Allocca, Romano, Lahm, Leoni, Sasso, Scarselli and Nicosia.)

Oncolytic virus (OV)-based immunotherapy is mainly dependent on establishing an efficient cell-mediated antitumor immunity. OV-mediated antitumor immunity elicits a renewed antitumor reactivity, stimulating a T-cell response against tumor-associated antigens (TAAs) and recruiting natural killer cells within the tumor microenvironment (TME). Despite the fact that OVs are unspecific cancer vaccine platforms, to further enhance antitumor immunity, it is crucial to identify the potentially immunogenic T-cell restricted TAAs, the main key orchestrators in evoking a specific and durable cytotoxic T-cell response. Today, innovative approaches derived from systems biology are exploited to improve target discovery in several types of cancer and to identify the MHC-I and II restricted peptide repertoire recognized by T-cells. Using specific computation pipelines, it is possible to select the best tumor peptide candidates that can be efficiently vectorized and delivered by numerous OV-based platforms, in order to reinforce anticancer immune responses. Beyond the identification of TAAs, system biology can also support the engineering of OVs with improved oncotropism to reduce toxicity and maintain a sufficient portion of the wild-type virus virulence. Finally, these technologies can also pave the way towards a more rational design of armed OVs where a transgene of interest can be delivered to TME to develop an intratumoral gene therapy to enhance specific immune stimuli.

Spiraea hypericifolia is a Eurasiatic species, distributed from SW Europe to C and SW Asia. In Italy, only the alien S. hypericifolia subsp. obovata was recorded, as naturalized in the Central Apennines. Spiraea flabellata was described from Abruzzo (Central Apennines, Italy) by Gussone in 1826 and is currently regarded as a synonym of S. hypericifolia subsp. obovata . Based on the study of living plants from locus classicus and the analysis of the original material traced in BOLO and NAP, S. flabellata should be referred instead to S. hypericifolia subsp. hypericifolia , a taxon reported here for the first time in Italy. The name S. flabellata is lectotypified with a specimen kept in NAP. Based on our study, S. hypericifolia subsp. obovata should be excluded from Italian flora. Spiraea hypericifolia subsp. hypericifolia should be considered native to Italy and added to the contingent of steppe plants of phytogeographic and conservation interest recorded in the Central Apennines. Finally, the conservation status assessment of S. hypericifolia subsp. hypericifolia according to IUCN categories and criteria, is proposed and discussed.

Background: The number of single ventricle patients undergoing Fontan palliation and surviving to adulthood worldwide has steadily increased in recent years. Nevertheless, the Fontan circulation is destined to fail. Ultimately, heart transplantation (HTx) remains the definitive treatment option. Due a shortage of organs, mechanical circulatory support in the form of ventricular assist devices (VADs) is widely used to bridge heart failure patients to HTx, but these devices have been mainly developed to address the needs of normal anatomies. A novel venous cannula has been developed as part of the EXCOR® VAD to provide subpulmonary support in these patients. Its clinical application is investigated in the "Registry to Assess the Safety and Feasibility of the Subpulmonary Support with the Novel Venous Cannula in Patients with Failing/Absence of the Right Heart" (RegiVe study, NCT04782232)., Methods: RegiVe is a multicenter, international, observational, prospective, non-randomized registry aiming to collect the routine clinical data of up to 20 patients. The primary endpoints address device performance and safety, while the secondary endpoints target organ status and overall safety (according to the Interagency Registry for Mechanically Assisted Circulatory Support - INTERMACS - definitions). Data analysis will be performed by means of descriptive statistics., Results: RegiVe has received the favorable opinion of an independent ethics committee and enrollment has recently started., Conclusion: RegiVe is the first study evaluating the use of a medical device specifically developed for subpulmonary support of failing Fontan patients. The study will provide important insight and further information on this cohort and help to improve a dedicated VAD strategy., Competing Interests: E. D. S., T. S., K.-J. S., and A. K. M. are employees of Berlin Heart GmbH. O. M. and F. D. R. received fees as EEPIG chairs. F. D. R. is proctor of Berlin Heart GmbH., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Ranuculus gracilis is endemic to the SE Euro-Mediterranean area and its presence in Italy is controversial. Based on analysis of the relevant literature, field surveys and examination of herbarium specimens, a revised distribution of this species in Italy is presented and its conservation status is assessed. Ranunculus agerii , described by Antonio Bertoloni from Bologna (Emilia-Romagna, Northern Italy), and R. schowii, described by Vincenzo Tineo from Vittoria and Terranova (Sicily), usually regarded as synonyms of R. gracilis , are here lectotypified and their taxonomic status discussed. Thanks to our study, the presence of R. gracilis in Italy is confirmed and, now, it is reported in a national conservation framework.

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Antibody-based cancer immunotherapy includes monoclonals against immune checkpoints (ICs), to modulate specific T cell responses against cancer. NK cells are a newly emerging target for immune checkpoint receptor inhibition in cancer immunotherapy, as ICs are also expressed on NK cells in various cancers. The latter cells are becoming attractive targets for cancer immunotherapy, as they are effector cells similar to CTLs, exerting natural cytotoxicity against primary tumor cells and metastasis, and they are able to distinguish tumor cells from healthy ones, leading to more specific anti-tumor cytotoxicity and reduced off-target effects. Thus, we decided to test the effects on isolated NK cells and T cell subpopulations of novel immunomodulatory mAbs, recently generated in our lab, in comparison with those in clinical use, such as ipilimumab and atezolizumab. Interestingly, we found that the novel anti-CTLA-4 (ID-1) and anti-PD-L1 (PD-L1&#95;1) antibodies are able to induce NK cell activation and exert anti-tumor effects on TNBC cells co-cultured with NK cells more efficiently than the clinically validated ones, either when used as single agents or in combinatorial treatments. On the other hand, ipilimumab was found to be more effective in activating T cells with respect to ID-1. These findings indicate that antibodies targeting different epitopes can have differential effects on different lymphocytes subpopulations and that novel combinations of mAbs could be suitable for therapeutic approaches aimed at activating not only T cells but also NK cells, especially for tumors lacking MHC.

Data on the long-term durability of rilpivirine (RPV) are still scarce. A two-center retrospective study was performed, including all people living with HIV (PLWH) treated with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)/RPV or tenofovir alafenamide (TAF)/FTC/RPV in the period January 2013-December 2019. Aims of the study were to assess the rate of discontinuation of the RPV single-tablet regimen (STR) and identify factors associated with the risk of discontinuation according to Cox's regression analysis. A total of 684 PLWH were enrolled. Mean duration of RPV-STR treatment was 192.5 (±99.5) weeks for 123 antiretroviral therapy (ART)-naïve participants (18%) and 173.3 (± 85.6) weeks for 561 ART-experienced study participants (82%). During the study period, the incidence of discontinuation was 7.7 per 100 person-years. The estimated proportions of discontinuation after 48 and 96 weeks were 5.6% and 13.4%, respectively. Causes of discontinuation were loss to follow-up (30%), side effects (15%), ART optimization (14%), virological failure (VF) (12%), death or transfer to another center (9%), low adherence (7%), drug interactions (6%), simplification to dual therapy (3%), and unknown (3%). No differences were observed in cumulative probability of discontinuation between ART-naïve and -experienced PLWH. Heterosexual (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.4-6.8) and mother-to-child (HR 5.3, 95% CI 1.8-15.3) transmission of HIV infection and history of previous VF (HR 1.7, 95% CI 1.2-2.5) were associated with higher risk of discontinuation. High RPV-STR effectiveness and durability were confirmed in our real-life population of PLWH. Given these data, RPV has the potential to be a drug for life in patients selected according to current guidelines.