原発性免疫不全症候群

BACKGROUND: Latent tuberculosis infection (LTBI) is more frequent among people living with human immunodeficiency virus (HIV) (PLHIV), in whom immunosuppression favors reactivation. However, data from sub-Saharan Africa remain limited. This study aimed to determine the prevalence of LTBI and identify its associated factors among adults living with HIV in Kinshasa. METHODS: An analytical cross-sectional study was conducted between May 2022 and October 2025 in nine HIV care centers in Kinshasa. Adult HIV-positive patients were consecutively recruited. LTBI was screened using the tuberculin skin test (TST) and/or interferon-gamma release assays (IGRAs). Socio-demographic, clinical, and immunological data, including CD4 cell counts, were collected. Associated factors were identified using multivariate logistic regression at a significance level of p < 0.05. RESULTS: Among 248 participants, 74.7% were women. The mean age was 45.5 ± 10.7 years, and the median CD4 count was 321 cells/µL (IQR: 281-390). Overall, 25.8% were IGRA-positive and 30.6% TST-positive, with 38.3% indeterminate IGRA results. The main factors associated with LTBI were CD4 count <200 cells/µL (IGRA: adjusted odds ratio [aOR] = 3.34; TST: aOR = 3.64), history of positive TST (IGRA: aOR = 2.50; TST: aOR = 2.78), and contact with an active TB case (IGRA: aOR = 2.94). CONCLUSIONS: The prevalence of LTBI among adults living with HIV in Kinshasa is high. Severe immunosuppression, prior exposure, and contact with active TB cases are key determinants. These findings highlight the importance of screening and preventive therapy to reduce progression to active tuberculosis.

BACKGROUND: Clinical trials in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS), an ultra-rare disease, have evaluated treatment response to the PI3Kδ inhibitor leniolisib using disease activity endpoints, including those measuring immunodeficiency and immune dysregulation. However, the relationship between disease activity endpoints and long-term clinical outcomes has not been quantified. METHODS: Data from a randomised controlled trial and its open-label extension (OLE) investigating leniolisib were used to evaluate associations between short-term disease activity endpoints and longer-term clinical outcomes. Both single time point and repeated measures analyses were conducted using linear regression modelling and random effects multilevel regression modelling, respectively. RESULTS: In total, 39 patients were included (≤6 years of follow-up). Improvements in multiple immunodeficiency and dysregulation disease activity endpoints were significantly associated with increases in the patient global assessment (PtGA) and the 36-item short form survey (SF-36) physical component score and mental component score (PCS/MCS). Increasing proportion of naïve B cells was associated with reduction in infection rates (2.3% fewer infections per 1% increase in naïve B cells). CONCLUSIONS: In this clinical trial setting, short-term improvements in immunodeficiency and dysregulation following treatment with leniolisib were associated with longer-term improvements in clinical outcomes, including infection rates and quality of life, for patients with APDS.

INTRODUCTION: The optimal duration of perioperative antibiotic prophylaxis for elective ostomy reversal in children remains unclear, and antibiotic regimens vary widely despite limited evidence supporting extended use. This study evaluated whether continuation of perioperative antibiotics beyond surgery completion reduces postoperative infectious complications in pediatric ostomy reversal. METHODS: A retrospective cohort study used the NSQIP Pediatric database and Surgical Antibiotic Prophylaxis files from 2021 to 2023. Children <18 years undergoing elective ostomy reversal were identified by CPT codes 44620, 44625, and 44626. Exclusion criteria included immunodeficiency, transplantation, malignancy, age <28 days, outpatient surgery, and missing antibiotic data. Patients were categorized as receiving antibiotics intraoperatively only versus postoperative continuation. The primary outcome was wound infection (superficial, deep, organ/space); secondary outcomes included pneumonia, UTI, length of stay, and days to discharge. RESULTS: Of 2064 patients (median age 331 days), 60.4% continued antibiotics postoperatively. On multivariate analysis, postoperative antibiotic continuation was not associated with reduced wound infection. Higher preoperative albumin was protective against wound infection. No differences were observed in infection subtypes, UTI, pneumonia, or length of stay. Among children <1-year, antibiotic continuation was not protective, while term birth was associated with increased wound infection risk (OR 2.63, 95% CI 1.24-5.65). CONCLUSION: Postoperative antibiotic continuation was not associated with reduced infectious complications following pediatric ostomy reversal. Preoperative nutritional optimization may play a greater role in reducing SSI than postoperative antibiotic continuation.

INTRODUCTION: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) among adults aged 50 and older presents an emerging challenge in China, hindered by reasons like insufficient health checks and low self-perceived HIV risk. To overcome these barriers and assist decision-makers in prioritizing interventions, it is critical to investigate HIV testing preferences in this population and identify which service characteristics are the preferred aspects, especially within the primary care setting. METHODS: From July 1 to October 30, 2025, a face-to-face, case 1 best-worst scaling (BWS) survey was performed to quantify older men's preferences for HIV testing across five cities in eastern, central and western Guizhou. Guided by the Consolidated Framework for Implementation Research, attributes were selected through prior literature review and qualitative study. We calculated the BWS scores, estimated the relative importance of each attribute and used the coefficients derived from the mixed logit models to calculate share of preference (SP) to interpret final results. Regression analyses were used to explore the heterogeneity of HIV testing preferences across the sample. RESULTS: A total of seven core attributes were identified in this BWS design. Among 338 respondents (mean age 61.2 ± 7.8 years), 71.3% resided in rural areas. The overall responses demonstrated 'comprehensive care' (SP 22.2%) and 'confidentiality' (SP 18.1%) were the most highly prioritized, followed by 'anxiety alleviation' (SP 14.6%), 'consultation context' (SP 13.5%) and 'clear explanation' (SP 13.1%). The least prioritized attributes were 'incentive' (SP 10.2%) and 'appointment' (SP 8.3%) for HIV testing services. Notably, significant heterogeneity in preferences was observed across subgroups, with demographic and socioeconomic characteristics identified as key sources of variation. Among the sample population, additional testing incentives were perceived as a more important attribute for older participants and those who had never tested before. CONCLUSION: Supplementing conventional clinic-based testing with comprehensive service delivery is a promising approach to potentially increase HIV testing uptake among men aged 50 and older in China. People also strongly prioritized the confidentiality of HIV test results in the primary care setting. Our findings provided implications for service providers and policymakers to develop client-centered, differentiated HIV testing strategies in China.

RIO is an ongoing phase 2 double-blind randomized placebo-controlled human trial. Sixty-eight adult men living with human immunodeficiency virus (HIV), who were predominantly white and initiated antiretroviral therapy (ART) during primary or early-stage infection, underwent treatment interruption and were randomly assigned to a group receiving one or two doses of two long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS and 10-1074-LS (arm A, n = 34) or saline (arm B, n = 34). The primary clinical study met its primary endpoint and was published elsewhere, demonstrating significantly delayed viral rebound and prolonged ART-free control in participants receiving bNAbs compared with placebo. The infusions were generally safe and well tolerated, with no study-related serious adverse events reported. The most common reported treatment-related adverse events were fatigue, lethargy and somnolence. Here we report on prespecified secondary analyses examining viral rebound, antibody sensitivity and reservoir dynamics, as well as prespecified exploratory analyses of rebound virus evolution and autologous antibody activity. Preinfusion reservoir measurements showed low levels of intact proviral HIV-1 DNA in circulating CD4+ T cells in both arms. The rebounding viruses in participants who received the antibodies showed significant selection for resistance to 10-1074-LS but not to 3BNC117-LS. Notably, there was a significant correlation between greater initial reservoir sensitivity to autologous antibodies and 10-1074 and time to rebound. Finally, comparison of preinfusion and prerebound HIV-1 proviral reservoir showed a decrease in intact but not defective proviruses in arm A but not in arm B. Together, these findings suggest that baseline humoral immunity and prolonged exposure to LS-bNAbs jointly shape post-treatment viral rebound dynamics in individuals who initiate ART during primary infection. ClinicalTrials.gov identifier: NCT04319367 .