Focusing on craniofacial bones, this study investigates morphological variation related to sexual dimorphism in order to deepen our understanding of human biological diversity and to provide new data from a contemporary reference sample. Accordingly, the research was guided by three objectives (i) identify the facial regions exhibiting the greatest sexual dimorphism using landmark-based geometric morphometric method; (ii) evaluate the reliability of discriminant models based on these dimorphic regions; and (iii) conduct exploratory analyses to assign sex classification probabilities to ancient subjects using the discriminant models derived from a contemporary reference sample. The reference sample comprised 44 skulls from subjects of known sex who died in 2024. The ancient sample included 4 skulls recovered from the Grotte de La Medecine (France), attributed to the chalcolithic period. Fourteen facial landmarks were digitized using 3DSlicer. Generalized Procrustes Analysis was performed to extract shape variables and standardized coordinates for statistical analysis. Thin-Plate Spline transformations quantified and visualized deformation amplitudes between the female and male shapes. Landmarks in the orbital showed the highest deformation amplitudes. Goodall F-test comparing male and female shapes across three facial regions revealed significant sexual dimorphism only in the orbital region and the global facial shape. Discriminant analysis demonstrated that the orbital region provided the highest classification accuracy (88.6%) compared to the global facial region (72.7%). The discriminant models yielded high probabilities of male and female sex classification for the ancient subjects. Using a reproducible method, comparable levels of accuracy to those reported in the scientific literature were achieved despite a relatively modest sample size. These findings further confirm the significant role of the orbital region in human craniofacial sexual dimorphism.
Accurate preoperative identification of extraprostatic extension (EPE) in prostate cancer (PCa) is important for treatment strategies. This retrospective study aimed to determine which MRI sequence provides the most accurate measurement of length of capsular contact (LCC) and maximum lesion radial distance (MaxRADD) for predicting EPE. We included 63 patients who underwent radical prostatectomy for biopsy-confirmed PCa and had preoperative multiparametric MRI (mpMRI) from 2018 to 2020. Two radiologists measured LCC and MaxRADD on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and dynamic contrast-enhanced (DCE) sequences. LCC was evaluated using 10 mm and 15 mm thresholds based on Prostate Imaging-Reporting and Data System (PI-RADS) and European Society of Urogenital Radiology (ESUR) guidelines. Histopathology was the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. 63 patients with 105 evaluable lesions were included. Significant differences were observed between the 10 mm and 15 mm LCC thresholds for predicting EPE. At 10 mm, DCE demonstrated the highest sensitivity (90.1%) and a 80.7% specificity. At 15 mm, DCE achieved higher specificity (94.7%) with 85% sensitivity. ROC analysis identified 14 mm on DCE as the optimal LCC threshold, reaching 90% sensitivity, 96.6% specificity (AUC:0.93). MaxRADD showed variable diagnostic performance, with the highest AUC on DCE (0.83), T2WI (0.80), DWI (0.78), and ADC (0.74), without significant differences. Combining LCC and MaxRADD slightly improved AUC (0.96 vs. 0.93 for LCC alone, p = 0.270). MaxRADD performed best on DCE at an 11 mm threshold (sensitivity 65%, specificity 88.5%). DCE provides the highest diagnostic performance for predicting EPE using LCC measurements, with a 14 mm LCC and 11 mm MaxRADD threshold yielding the best overall accuracy. Combining LCC and MaxRADD numerically increased AUC (0.96 vs. 0.93), however without significant differences in EPE prediction (p = 0.270).
Human papillomavirus (HPV) vaccine coverage (VC) remains suboptimal in many countries. The PrevHPV national research programme aimed to codevelop and evaluate a three-component intervention including: 'education and motivation' of adolescents, 'at-school vaccination', 'general practitioners (GPs)' training'. We assessed its impact on VC at one year through a cluster randomized trial (July 2021-April 2022) conducted in French municipalities (clusters) receiving 0, 1, 2, or 3 components. The outcomes (≥ 1-dose and full HPV VC at one year among 11-14-year-olds) were estimated using data from the national health reimbursement database and data collected during the trial. We performed intention-to-treat and post-hoc analysis adjusted for the dose of intervention using cluster-level linear models. Ninety-one municipalities were included. 'At-school vaccination' significantly increased ≥ 1-dose VC, in both intention-to-treat (+ 2.85 percentage points (pp), 95%CI = 0.62 to 5.09) and post-hoc analysis (+ 4.60 pp, 95%CI = 1.79 to 7.41). No significant effects were found for the other components. Results were similar for full VC. 'At-school vaccination' significantly increased VC only in municipalities with the lowest access to GPs. School-based vaccination was effective in increasing HPV VC in the medium term and may reduce VC healthcare access-driven territorial disparities. Challenges remain in parental engagement and consent for vaccination at school.Trial registration: Clinicaltrials.gov, NCT04945655. Registered 30 June 2021.
The COVID-19 pandemic negatively affected residents of long-term care facilities (LTCFs). This situation highlighted the necessity to translate evidence-based policies and practices into this setting. However, implementing innovations represents a challenge for LTCFs. This study aims to identify the facilitators and barriers to the implementation of innovations in Canadian LTCFs. We conducted a longitudinal correlational study involving different LTCFs participants and the use of the Organizational Readiness for Knowledge Translation (OR4KT) measurement tool before and after the implementation of an innovation. Only data collected at T1 were considered in the analysis due to the low response rate obtained at T2. A mixed-model effect with a random effect for LTCFs was used to account for within organization dependency on responses. In total, 256 respondents from 55 (60.4%) LTCFs participated in the study of which 107 participants were high and middle-level managers, and 149 were non-managerial staff. Variations in OR4KT scores were explained by some organizational factors. The province of location of the LTCF emerged as a significant factor for five subscales of the OR4KT as well as for the total score. The presence of a medical director and belonging to a chain (an organization with multiple LTCFs) seemed to be associated with higher OR4KT scores. Successful LTCF innovation implementation may rely on the geographical administration of healthcare (e.g., the province), the presence of a medical director and the organizational contextual factors between the different actors of LTCFs and the health system.
To optimize the management of male urinary tract infections, it is essential to analyze the various pharmacokinetic and pharmacodynamic parameters in the different organs of the male urinary tract. In the literature, the quantity and quality of data vary considerably depending on the class of antibiotics and the methodological approaches used. Beta-lactams achieve effective concentrations in prostate tissue, the testes, and urine, but reach only limited levels in prostatic secretions. Fosfomycin reaches therapeutic concentrations in prostate tissue, prostatic secretions, seminal fluid, bladder tissue, and urine. Trimethoprim-sulfamethoxazole reaches effective concentrations in prostate tissue, the testes, and urine. Only trimethoprim reaches effective concentrations in prostatic secretions and seminal fluid. Fluoroquinolones have the most favorable pharmacokinetic and pharmacodynamic profile and achieve therapeutic concentrations in prostate tissue, prostate secretions, seminal fluid, the testes, bladder tissue, and urine, as well as excellent intracellular diffusion and significant antibiofilm activity. The pharmacokinetics of aminoglycosides in the prostate and testes remain poorly characterized, despite the high concentrations observed in the kidneys and urine. Nitrofurantoin achieves a low plasma concentration, indicating limited tissue distribution. Azithromycin and doxycycline exhibit significant concentrations in prostatic tissue. Further research is needed to enhance understanding of the pharmacokinetics and pharmacodynamics of antibiotics in the male urinary tract, particularly in the context of growing antibiotic resistance.
Fibroblast growth factor receptor (FGFR) alterations including mutations, fusions and amplifications, are known oncogenic drivers. FGFR tyrosine kinase inhibitors (FGFRi) have demonstrated clinical activity in patients with FGFR3-driven urothelial carcinoma and FGFR2-driven cholangiocarcinoma. This study aims to describe outcomes with FGFRi according to alteration and tumor type. We retrospectively assessed data from patients with FGFR alterations treated by an FGFRi in multiple clinical trials and in routine care at Gustave Roussy. Among 158 patients treated by an FGFRi from February 2011 to March 2025, 27 had FGFR amplifications, 76 FGFR fusions, and 55 FGFR mutations. FGFR fusions, most common in cholangiocarcinoma, were associated with the most favorable outcomes with an overall response rate (ORR) of 45.9%, median progression free survival (PFS) and overall survival (OS) of 7.3 and 19.7 months, respectively. FGFR amplifications, found predominantly in breast cancer, were associated with the poorest outcomes (ORR of 11.1%, median PFS and OS of 2.1 and 9.9 months, respectively). FGFR mutations, observed mainly in urothelial carcinoma, showed intermediate efficacy (ORR of 30.9%, median PFS and OS of 4.7 and 12.4 months, respectively). Among the 22 patients who received a second FGFRi, outcomes were inferior to firsts exposure (ORR of 13.6% vs 47.6% and median PFS of 3.8 vs 8.5 months). Clinical activity of FGFRi was heterogenous across FGFR alteration and tumor types. FGFR fusions and mutations were associated with greater benefit, whereas amplifications were not. Further investigation of resistance mechanisms and development of next-generation FGFRi are needed.
Biallelic variants in the minor spliceosomal gene RNU4ATAC were successively identified in Taybi-Linder/MOPD1 (Microcephalic osteodysplastic primordial dwarfism type I), Roifman, and Lowry-Wood syndromes, characterized by variable microcephaly, short stature, neurodevelopmental impairment, skeletal dysplasia, and immunodeficiency. Two-thirds of the reported individuals present with Taybi-Linder syndrome, the first described and most severe form. We collected clinical and molecular data from individuals with biallelic RNU4ATAC variants through various French and European networks and clinics, to refine the phenotypic spectrum of RNU4ATAC-opathies. We enrolled 69 participants and identified 18 new pathogenic variants. We report a significant proportion of attenuated/atypical presentations, novel rare symptoms, and, unexpectedly, a broad spectrum of autoimmune/inflammatory manifestations, affecting nearly half of the participants. Integrating our data with the 109 published cases, we propose a novel classification based on the main manifestations, immunodeficiency and microcephalic primordial dwarfism. Using computer-assisted facial analysis, we also demonstrated the existence of a specific dysmorphic pattern in RNU4ATAC-opathies, distinct between some sub-syndromes. We present a large cohort of individuals with RNU4ATAC-opathies and expand the phenotypic spectrum to pauci-symptomatic forms, indicating that these diseases are likely to remain underdiagnosed.
LDB1 encodes transcriptional regulator protein LIM domain-binding protein 1, which plays an important role in neurogenesis. Few C-terminal likely gene-disrupting (LGD) variants have been reported in the literature in individuals with congenital ventriculomegaly. Through international collaboration, we now assembled a cohort of 16 individuals with de novo variants affecting various regions of LDB1. Eleven variants affect either the whole gene or the N-terminal dimerization domain (including gene deletions, as well as nonsense-mediated mRNA decay (NMD)-sensitive LGD and missense variants), and five variants (missense or NMD-escaping LGD variants) affect only the C terminus of LDB1 containing the LIM interaction domain. All individuals showed variable neurodevelopmental phenotypes, including developmental delay and behavioral anomalies. In line with literature reports, individuals harboring C-terminal variants additionally presented with ventriculomegaly, which suggests a potential genotype-phenotype correlation. In accordance, we found diverging pathomechanisms in vitro: N-terminal missense variants disrupt homodimerization of LDB1, likely leading to a loss of function, while C-terminal variants impair interaction with the essential partner LHX2 in a dominant-negative manner. These findings were confirmed in vivo in Drosophila melanogaster. Toxicity of overexpressed human LDB1 in Drosophila was not observed with N-terminal missense variants but was exacerbated by C-terminal variants. Similarly, phenotypes associated with LDB1/chi loss were rescued by overexpression of wild-type LDB1 but not by LDB1 harboring N-terminal missense variants or by C-terminal variants that even worsened phenotypes. In summary, our findings indicate that de novo variants in LDB1 are linked to two overlapping but distinct neurodevelopmental phenotypes based on variant location and propose two separate pathomechanisms underlying LDB1-related neurodevelopmental disorders.
Parity has been reached among French residents in the intensive care medicine (ICM) specialty; however, concerns about underrepresentation of women in leadership position and gender discriminations remain. We hypothesised that perception of gender inequity differs between female and male ICM residents and increases along the ICM training. This nationwide observational closed-survey investigated how ICM residents experienced their medical curriculum, how they perceived the ICM specialty, and the potential reasons for women to be underrepresented in leadership position. Among 113 residents who responded to the survey, 63 (55.6%) were females, and 85 (75.2%) were beginners. Twenty-nine (25.7%) answered to be always or often self-confident, and this number was lower in female than in male residents (14.3% versus 40.8%, p = 0.003). Women had less often than men the feeling to keep up with the situation along their medical training (39.7% versus 70.8%, p = 0.004). Societal injunctions to prioritise family over professional responsibilities were more often considered as barriers to leadership position by women than by men (75.8% versus 51.1%, p = 0.015). Fully trained residents agreed more frequently than beginners with the 2 following reasons associated with gender gap in ICM leadership position: men being more ambitious (31.1% versus 9.4%, p = 0.024) and professional environment discriminating against women (64% versus 46.2%, p = 0.017). Experience of non-physical sexual harassment was very common in female residents, with 74.6% of them reporting to have been directly subjected to jokes of a sexual nature (versus 28.6% of men, p = 0.001) and 49.2% of them to have been victims of allegations with humiliating connotation (versus 22.4% of men, p = 0.007). Female ICM residents reported more often the feeling of not coping with their medical training, the lack of self-confidence, and non-physical sexual harassment than men. Reported awareness of a less supportive institutional environment to women academic career and of difference in assertiveness between men and women increased along advancement in ICM training suggesting room for interventions.
The clinical and biological heterogeneity of major depressive disorder (MDD) may reflect the aggregation of different conditions with distinct pathologies under a single diagnostic label. Neuroanatomical heterogeneity in MDD was examined using a harmonized, age- and sex-matched sample from the ENIGMA MDD consortium (N = 5146; age range: 9-82 years; 64% female). Analyses of global neurostrucutral variability revealed greater cortical thickness heterogeneity in MDD compared with healthy controls (Cohen's d = -0.26). Regionally, increased variability in cortical thickness was most prominent in the cingulate (+6.1 to +6.6% more variation in MDD) and insular (+5.8%) cortices, as well as in the frontal (+5.7 to +6.8%) and temporal (+6.1 to +6.8%) lobes. Heterogeneity in cortical thickness was more pronounced among patients using antidepressant medication (Cohen's d = -0.39). Patient-specific analyses further showed that individuals with markedly increased cortical thickness variability (<5th percentile relative to the normative range) exhibited greater depressive symptom severity than those within the normative range (5th-95th percentile; Cohen's d = 0.19-0.36). Overall, the results indicate that neuroanatomical heterogeneity in MDD is primarily expressed in cortical thickness, offering refined insights into the neurobiological complexity of structural alterations associated with depression. These findings could guide future stratification efforts examining whether regionally confined changes in cortical thickness within areas of pronounced variability reflect clinically meaningful patient subgroups.
The combination of antiangiogenic therapy with immune checkpoint blockade has demonstrated significant clinical benefits in various cancers, however, the precise mechanisms of action on the immune system are not fully understood. In particular, the early intratumoral immune responses induced by angiogenesis inhibition remain unclear. Using preclinical models of colorectal cancer, we examined the immune changes elicited by combined vascular endothelial growth factor receptor-2 (VEGFR-2) and programmed cell death protein-1 (PD-1) blockade. Our findings reveal that CD8 T cells respond directly and early to VEGFR-2 inhibition, preceding the acquisition of overt cytotoxic function. Shortly after treatment, intratumoral CD8 T cells expanded and produced interleukin-10 (IL-10). Unexpectedly, this CD8 T cell-derived IL-10 promoted the recruitment of natural killer (NK) cells into tumors. Recruited NK cells subsequently gained effector activity and produced granulocyte-macrophage colony-stimulating factor, which supported macrophage maturation and the induction of CXCL11. This sequence of events enhanced secondary CD8 T-cell infiltration and sustained antitumor immune activity. Disruption of IL-10 signaling or NK-cell function eliminated the therapeutic benefit of combined VEGFR-2 and PD-1 blockade, whereas regulatory T-cell depletion further improved tumor control. Together, these findings identify an unanticipated role for CD8 T cell-derived IL-10 in coordinating early innate and adaptive immune responses following angiogenesis inhibition and define an immune program initiated by VEGFR-2 blockade that is required for therapeutic efficacy in two preclinical colorectal cancer models.
Urinary tract infections (UTIs) in men, though less frequent than in women, represent a significant clinical challenge due to their increasing incidence with age and distinct microbiological profiles. This expert review analyzed data of urine cultures in men with community-acquired UTIs, collected from emergency departments of 15 french hospitals, from the private laboratory group Atoutbio (21 sites in Meurthe-et-Moselle and the Vosges French departments, alongside primary care records from the AntibioClic tool and the PRIMO database, to characterize the bacterial epidemiology of community-acquired male UTIs in France. Escherichia coli (39-40%) dominated, followed by Enterococcus faecalis (13-15%), Klebsiella pneumoniae (6-8%), and Proteus mirabilis (5-6%). Resistance rates were as follows amoxicillin (47-53.5%), amoxicillin-clavulanate (24-35.7%), trimethoprim-sulfamethoxazole (25.4-31.5%), and fluoroquinolones (16.3-20.2%). Resistance to third-generation cephalosporins (6.6-9.3%) and mecillinam (6.8-8.9%) was lower, while fosfomycin (1.4-1.5%) and nitrofurantoin (0.4-0.7%) retained high susceptibility. Extended-spectrum β-lactamase (ESBL)-producing E. coli ranged from 2 to 8.4%, with carbapenemase producers remaining rare (0.1%). Resistance was higher in men >65 years, particularly in nursing homes, where 3GC resistance reached 15-18%. « Emerging uropathogens » (Aerococcus urinae 1-1.1%, Actinotignum schaalii 0.1-0.4%) were rare. This study highlights the greater microbial diversity in male UTIs compared to women and underscores the need for systematic urine culture, susceptibility testing, and empirical therapy tailored to resistance patterns, age, and risk factors.
Suppressive myeloid cells play a central role in cancer escape from anti-tumor immunity and exert multiple pro-tumoral activities, including the promotion of cancer cell survival, invasion, and metastasis. Recent evidence suggests that certain subsets may also influence tumor heterogeneity and cellular plasticity. However, their role in cancer stem cell promotion and plasticity and the underlying molecular mechanisms have yet to be deciphered. Here we demonstrate that human immunosuppressive myeloid cells, generated in vitro or isolated from patients with breast cancer, induce cancer stem-like cells exhibiting mesenchymal features. This cancer-stemness-inducing function was restricted to a CD52-expressing myeloid subset. Single cell transcriptomic- and surface proteome-based interactome analyses identify membrane-bound TGF-β1 as a potential mediator of this effect. Functional inhibition of the TGF-β1 pathway blocks stem-like feature induction by suppressive myeloid cells. These results provide insights into the cancer stemness-promoting capacity of suppressive myeloid cells and its associated molecular mechanisms in breast cancer.
Exercise-based heavy lifting has been suggested to challenge pelvic organ support, yet no study has investigated this in women at risk of pelvic organ prolapse. This study aimed to investigate the immediate impact of heavy weightlifting on pelvic floor morphometry in premenopausal, vaginally parous women trained in exercise-based heavy lifting. Participants without symptoms of vaginal bulge attended a heavy weightlifting session (heavy barbell back squats [5 × 5 repetitions at 80% one repetition maximum]). Pelvic floor morphometry was measured before and immediately after the session. Bladder neck and rectal ampulla positions, anorectal and levator plate angles, levator anteroposterior distance, and levator hiatal area were assessed using transperineal ultrasound at rest, during bearing down, and during pelvic floor muscle contraction, in supine and standing positions. The maximal vaginal descent was assessed using the Pelvic Organ Prolapse Quantification in supine. Thirty-seven women participated in the study. Compared to pre-lifting, immediately after lifting the anorectal angle at rest was larger in supine and standing (p ≤ 0.05); during pelvic floor muscle contraction the bladder neck was more caudal in supine (p < 0.001) and the levator hiatal area was larger in standing (p = 0.02); during bearing down the levator plate angle was smaller in standing (p = 0.002) and the levator hiatal area was larger in supine (p = 0.01). No other significant pre-post changes were found. In asymptomatic, trained, premenopausal, vaginally parous women, a single heavy lifting session may induce small immediate pelvic floor morphometric changes, with minor impact on organ support, as shown by stable bladder neck, rectal ampulla, and vaginal wall measures.
Heart cancer or metastasis is very rare, yet the heart is highly vascularized and mechanically pumps blood flow through our body. Recent findings from Ciucci et al. show that mechanical load in the beating heart suppresses cancer growth via Nesprin-2-dependent mechanotransduction, which changes histone methylation and chromatin compaction to keep proliferation genes less active in cardiac tumor cells.
Severe burns lead to intense and prolonged systemic inflammation and high rates of organ failure and major complications such as acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and mortality. Although corticosteroids have shown benefits in various critical care settings, no adequately powered randomized controlled trial has yet evaluated their effect in burn patients. The DEXA-BURN trial aims to assess whether early administration of dexamethasone reduces the incidence of major complications (moderate-to-severe ARDS or stage 2-3 AKI) and all-cause mortality in adults with severe burns. DEXA-BURN is a multicenter, randomized, placebo-controlled, double-blind trial conducted in 10 French intensive care units. Adult patients with ≥ 20% total body surface area (TBSA) burns, admitted within 24 h of injury and requiring mechanical ventilation, will be randomized (1:1) to receive either dexamethasone (0.2 mg/kg/day IV for 5 days) or placebo. Two endpoints are pre-specified and evaluated using a hierarchical testing strategy: (1) major complications within 28 days (moderate-to-severe ARDS or AKI KDIGO stages ≥ 2); and, if statistically significant, (2) all-cause mortality at day 90. Secondary endpoints include nosocomial infections, ventilator-free days, intensive care unit /hospital stay, CRP trajectory, and steroid-related adverse events. A total of 478 patients will be enrolled. Analyses will follow the intention-to-treat and modified intention-to-treat principle. This trial will provide high-quality evidence on the effectiveness and safety of corticosteroid therapy in the acute management of severely burned patients. Findings may inform future guidelines and improve critical care practices for this understudied population with a high risk of mortality. EudraCT: 2024-517708-12-00; ClinicalTrials.gov: NCT06968559. Registered on April 22, 2025.
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SSc is associated with increased malignancy risk, a growing cause of mortality in SSc. However, standardised incidence ratios (SIR) vary widely across studies and different malignancy subtypes. This meta-analysis aimed to determine the SIR of different malignancy subtypes and the temporal relationship with SSc diagnosis. A systematic review and meta-analysis were conducted by searching Embase, MEDLINE and Cochrane Library databases from inception to 7 December 2024. Cohort studies reporting SIRs of malignancies in SSc patients were included. Studies where SIR was not reported were excluded. Random-effects models were used to calculate pooled estimates, while study quality was assessed using the Newcastle-Ottawa Scale. This review is registered on PROSPERO (CRD42023445876). Thirty-one cohort studies comprising at least 32,134 SSc patients were included. Overall malignancy risk was significantly increased (SIR 1.66; 95% CI 1.32 - 2.08). Highest risks were observed for esophageal, liver, cervical, lung, and haematological malignancies (SIR 3.35 - 13.95), while breast malignancy showed modest increased risk (SIR 1.34, 95% CI 1.00 - 1.80) that was not statistically significant. High-quality studies confirmed these associations except for esophageal malignancy, with only one high quality study for liver malignancy. There was a mean interval of 7.4 years (95% CI 5.3 - 9.5) between SSc and malignancy diagnosis. Our findings confirm an increased malignancy risk, particularly lung, haematological and cervical malignancies, and an approximate 7-year interval between SSc diagnosis and malignancy development. Further studies are needed to clarify the risk factors for different malignancy subtypes to develop cancer screening strategies. NIL.
Lenacapavir (LEN) with an optimized background regimen (OBR) was evaluated in a French cohort of participants with multidrug-resistant human immunodeficiency virus (HIV) via compassionate use. Adults (n = 42) with HIV-1 (PLWH1, n = 33) or HIV-2 (PLWH2, n = 9), receiving at least 1 dose of LEN plus OBR, were prospectively followed between January 2021 and December 2023. The primary endpoint was virological suppression (plasma HIV-1 RNA [VL] <50 copies/mL at week 26 (W26)) or maintenance, using the US Food and Drug Administration Snapshot algorithm. Secondary endpoints included long-term VL, resistance emergence, LEN plasma concentration, and drug safety. At baseline, PLWH1 presented with a median VL of 4.0 log10 copies/mL with 14 of 33 (42%) having VL <50 copies/mL, while PLWH2 had 3.0 log10 copies/mL (with baseline VL <50 copies/mL for 3). By W26, virological suppression was achieved or maintained in 67.0% (95% CI, 48.2%-82.0%) of PLWH1, with a mean CD4+ increase of +86 cells/μL. In PLWH2, virological suppression occurred in only 22.0% (95% CI, 2.8%-60.0%), with CD4+ counts rising by +27 cells/μL. Emergence of LEN resistance was documented in 1 PLWH1 (Q67H) and 3 PLWH2 (all N73D). The median (IQR) LEN plasma concentration was 43 (31&ndashng/mL after 26 weeks of subcutaneous injections. Tolerance was acceptable with 31% reported injection site reactions leading to discontinuation in 2 patients, and no grade 3/4 treatment-related adverse events occurred (2 deaths unrelated to treatment). LEN plus OBR showed robust efficacy and safety in PLWH1 but limited antiviral activity in PLWH2 due to limited OBR. These findings support LEN as an effective option in highly treatment-experienced PLWH1, while underscoring challenges for PLWH2.