The investigators plan to conduct an R61/33 hybrid type 2 implementation-effectiveness trial that includes 1) a one-year exploratory R61 phase that will enable the development of the intervention protocol needed for the R33 trial phase including concrete R61 phase milestones; 2) a four-year R33 phase that will include a concurrent implementation evaluation and a randomized control trial.

开始日期2026-06-01

申办/合作机构

Duke University

[+3]

NCT07516548

/ Not yet recruitingN/AIIT

Pharmacokinetic Study of Long-acting Antiretrovirals and Contraceptive Options in HIV Prevention

This study is being done to understand how long-acting injectable cabotegravir (CAB-LA) used for HIV pre-exposure prophylaxis (PrEP) and hormonal contraceptive methods affect each other when used at the same time. Women who are already using CAB-LA or not using PrEP will choose to join one of several groups based on whether they use injectable contraceptive (IM DMPA), an etonogestrel implant, or no hormonal contraceptive. Participants will have study visits every 4 to 12 weeks for up to 12 or 24 weeks after starting a contraceptive method to collect blood samples and measure levels of CAB-LA and hormone concentrations. The study will compare these levels to see if taking CAB-LA changes hormone concentrations or if using hormonal contraception changes CAB-LA drug levels. Safety, side effects, satisfaction, and continuation of CAB-LA PrEP and contraceptive methods will also be evaluated.

开始日期2026-06-01

申办/合作机构

The University of Alabama at Birmingham

[+3]

NCT07346508

/ Not yet recruitingN/A

Project SPEED - Streamlined Protocol for Early Engagement and Delivery of HIV Prevention With Long-acting Injectable Cabotegravir: A Nurse-driven Protocol

Project SPEED (Streamlined Protocol for Early Engagement and Delivery of HIV Prevention) is a pragmatic, cluster randomized implementation study evaluating a nurse-driven model for delivering long-acting injectable cabotegravir (LAI-CAB) for HIV pre-exposure prophylaxis (PrEP) within local public health departments (LPHDs) in Missouri. Although LAI-CAB is a highly effective HIV prevention strategy, access remains limited in many rural and resource-constrained settings due to workforce shortages and barriers to specialty care.
In this study, LPHDs are randomized to either implement a structured nurse-led PrEP delivery protocol (SPEED intervention) or continue current standard practices. At intervention sites, trained registered nurses assess PrEP eligibility, provide HIV and sexually transmitted infection testing, administer LAI-CAB injections under standing orders, and support ongoing follow-up as part of routine public health services. Control sites continue their usual workflows without additional training or standardized PrEP delivery processes introduced by the study.
The study uses an effectiveness-implementation hybrid type III design and is guided by established implementation science frameworks to evaluate reach, adoption, implementation, and sustainability of the nurse-driven model. Participants receiving care at participating LPHDs are followed for up to 48 weeks.
Project SPEED aims to generate real-world evidence on whether a nurse-driven approach can expand access to long-acting HIV prevention in public health settings, particularly in rural and underserved communities, and to inform scalable strategies for broader implementation of LAI-CAB PrEP.

开始日期2026-04-01

申办/合作机构

KC CARE Clinic

100 项与卡替拉韦钠相关的临床结果

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100 项与卡替拉韦钠相关的转化医学

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100 项与卡替拉韦钠相关的专利（医药）

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1,322

项与卡替拉韦钠相关的文献（医药）

2026-12-31·JOURNAL OF DERMATOLOGICAL TREATMENT

Long-term efficacy and tolerability of clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel for acne: pooled results from two 6-month studies

Article

作者: Tanghetti, Emil A. ; Wroblewski, Karol ; Ghannoum, Mahmoud ; Harper, Julie C. ; Kircik, Leon H. ; Baldwin, Hilary ; Draelos, Zoe D. ; Gold, Linda Stein

AIM:

Given the chronic nature of acne, two 6-month studies were conducted to evaluate the long-term efficacy and tolerability of clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB)-the only approved triple-combination acne topical-and its effects on scarring/dyspigmentation in participants with moderate to severe acne.

MATERIALS AND METHODS:

Data were pooled from 2 identical, open-label, single-center studies conducted in participants (N = 50) aged ≥12 years with Investigator's Global Assessment (IGA) score of 3/4. Endpoints included change from baseline in IGA score, inflammatory/noninflammatory lesions, skin appearance (dryness, postinflammatory hyperpigmentation [PIH], postinflammatory erythema [PIE]), and scarring. Adverse events and tolerability (itching, burning, redness, swelling) were assessed.

RESULTS:

At week 24, 67% of participants achieved treatment success, and significant reductions from baseline in inflammatory (88%) and noninflammatory (68%) lesions were observed (p < 0.001, both). Significant reductions in scarring (33%), investigator- and participant-assessed PIH (71%; 78%, respectively), and PIE (77%; 77%, respectively) were demonstrated (p < 0.001, all). Most participants (>70%) reported no tolerability issues throughout the studies. Seven adverse events occurred; 4 were related to CAB, and 3 led to study discontinuation (BPO allergy [n = 2], irritant contact dermatitis to BPO [n = 1]).

CONCLUSIONS:

These findings suggest that CAB is an appropriate and effective topical option for the long-term treatment of acne vulgaris.

2026-12-31·HIV Research & Clinical Practice

Successful initiation of fully parenteral antiretroviral therapy in a treatment-naïve person with HIV-1 infection and intestinal failure

Article

作者: Sram, Krystof ; Lhotan, Jakub ; Jilich, David ; Sevela, Stanislav ; Rozsypal, Hanus

INTRODUCTION:

In patients with severe surgical and gastrointestinal complications, standard oral combination antiretroviral therapy (ARV) may be temporarily impossible. Long-acting cabotegravir/rilpivirine (CAB/RPV LA) is approved for virologically suppressed individuals pretreated with oral therapy, but data on its use in treatment-naïve, critically ill patients with absent enteral absorption are extremely limited.

CLINICAL PRESENTATION:

We report a 26-year-old male admitted with fulminant hypertriglyceridaemic necrotizing pancreatitis complicated by abdominal compartment syndrome, multiple laparotomies, open abdomen with enteric fistulae, short bowel syndrome type I, chronic intestinal failure requiring parenteral nutrition, portal vein thrombosis, and prolonged intensive care. HIV-1 infection was diagnosed early (HIV RNA 5,000 copies/mL; CD4+ 780 cells/µL). Within three months, HIV RNA rose to 320,000 copies/mL and CD4+ declined to 570 cells/µL. Given absent gastrointestinal passage, standard ARV was initially deferred, but rapid virological rebound necessitated urgent treatment. An off-label fully parenteral regimen was initiated: intravenous zidovudine (AZT) with intramuscular CAB/RPV LA. Therapy was well tolerated alongside surgery, parenteral nutrition, antimicrobials, and anticoagulation. HIV RNA decreased to <20 copies/mL within 65 days and remained suppressed, with CD4+ recovery. Intravenous AZT was discontinued after 35 days, and CAB/RPV LA continued as maintenance during recovery and home parenteral nutrition.

DISCUSSION:

Fully parenteral ARV, including CAB/RPV LA, may provide a safe and effective bridge to durable viral suppression in patients with absolute contraindications to oral therapy, warranting further evaluation.

2026-07-01·INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES

Virological outcomes of PWH who discontinued cabotegravir/rilpivirine long-acting therapy in a real-world context

Article

作者: Marchetti, Giulia ; Squillace, Nicola ; Gagliardini, Roberta ; Giacomelli, Andrea ; Monforte, Antonella d'Arminio ; Antinori, Andrea ; Raccagni, Angelo Roberto ; Bana, Nicholas Brian ; Muccini, Camilla ; Mazzotta, Valentina ; Tavelli, Alessandro ; Saracino, Annalisa

The aim of this study was to describe virological outcomes in people with HIV (PWH) after discontinuation of long-acting (LA) cabotegravir (CAB) plus rilpivirine (RPV). All PWH enrolled in the Icona Cohort who discontinued CAB/RPV LA and had at least one follow-up after discontinuation were included. A total of 84 out of 805 (10.4%) PWH discontinued CAB/RPV, mainly due to toxicity or adverse events (67.9%). Most individuals (72.6%) returned to the same oral antiretroviral regimen used prior LA therapy. The 12-month cumulative probability of discontinuing oral ART after CAB/RPV was 19.9% (95% confidence interval [CI] 11.9-32.2%). After switching back to oral ART all individuals except one maintained or achieved HIV RNA levels below 50 copies/mL. These findings suggest that PWH who discontinue LA CAB/RPV and resume oral ART maintain or achieve high rates of virologic suppression.

411

项与卡替拉韦钠相关的新闻（医药）

2026-05-13

·北京医学感染与传染研究

抗菌化疗杂志81卷 1-5期

Journal of Antimicrobial Chemotherapy Volume 81, Issue 1抗菌化疗杂志81卷 1期 https://academic.oup.com/jac/issue 50th Anniversary Collection（50周年纪念合集） Review（综述） 1 Artificial intelligence for improving decision-making in bacterial infection management: a narrative review 人工智能在改善细菌感染治疗决策中的应用：一项叙述性综述 Anisia Talianu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf470, https://doi.org/10.1093/jac/dkaf470 Reviews（综述） 2 Evolving landscape of methicillin-resistant Staphylococcus pseudintermedius: the emergence of new epidemic waves across Europe, Asia and North America 耐甲氧西林中间型葡萄球菌的演变格局：欧洲、亚洲和北美洲新流行浪潮的出现 Lillian Rose Giarratana and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf340, https://doi.org/10.1093/jac/dkaf340 3 Azithromycin resistance in non-typhoidal Salmonella: a review 非伤寒沙门氏菌对阿奇霉素的耐药性：综述 Zhe Zhu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf341, https://doi.org/10.1093/jac/dkaf341 4 Antibiotic pharmacodynamics: from MIC to advanced metrics and their applications 抗生素药效动力学：从最低抑菌浓度到高级指标及其应用 Malin Andersson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf374, https://doi.org/10.1093/jac/dkaf374 5 Progress in the study of drug resistance mechanism of Bacillus cereus 蜡样芽孢杆菌耐药机制研究进展 Yuhang Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf399, https://doi.org/10.1093/jac/dkaf399 6 The curious constraints on clofazimine 氯法齐明的奇特限制 Maple Goh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf430, https://doi.org/10.1093/jac/dkaf430 7 Antiplasmid systems: a novel strategy to combat antibiotic resistance 抗质粒系统：对抗抗生素耐药性的新策略 Mohd Asim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf472, https://doi.org/10.1093/jac/dkaf472 Systematic Review（系统综述） 8 Coccidioidomycosis in Europe: a systematic literature review of epidemiology, treatment and outcomes 欧洲球孢子菌病：流行病学、治疗和预后的系统文献综述 Priya Shastri and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf407, https://doi.org/10.1093/jac/dkaf407 9 Systematic review of antimicrobial pharmacokinetic/pharmacodynamic indices in murine thigh and hollow fibre dose fractionation studies analysed with a standard method 用标准方法分析小鼠大腿和空心纤维剂量分次研究中的抗菌药物药代动力学/药效动力学指数的系统综述 Najla Alabdulkarim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf446, https://doi.org/10.1093/jac/dkaf446 Virtual Roundtable（虚拟圆桌会议） 10 Procalcitonin in the management of lower respiratory tract infection and sepsis 降钙素原在下呼吸道感染和败血症治疗中的应用 Ramy H Elshaboury and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf298, https://doi.org/10.1093/jac/dkaf298 Original Research（论著） 11 Model-based assessment of letermovir pharmacokinetics in allogeneic haematopoietic stem cell transplant recipients 来特莫韦在异基因造血干细胞移植受者中药代动力学的基于模型的评估 Chrisoula Tahtsidou and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf427, https://doi.org/10.1093/jac/dkaf427 12 In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci strains isolated from patients with infective endocarditis 体外试验评估依拉环素（CF-301）对甲氧西林敏感或甲氧西林耐药金黄色葡萄球菌及凝固酶阴性葡萄球菌（从感染性心内膜炎患者中分离）的活性 María-Alexandra Cañas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf435, https://doi.org/10.1093/jac/dkaf435 13 Evaluation of subcutaneous amoxicillin/clavulanic acid pharmacokinetics as an alternative to the intravenous route in older patients—the PhASAge Study 评估皮下注射阿莫西林/克拉维酸药代动力学作为老年患者静脉给药替代方案——PhASAge研究 Nicolas Grégoire and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf381, https://doi.org/10.1093/jac/dkaf381 14 Real-life use of isavuconazole in Spanish children and adolescents 西班牙儿童和青少年中艾沙康唑的实际使用情况 Natalia Mendoza-Palomar and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf394, https://doi.org/10.1093/jac/dkaf394 15 No pharmacovigilance signal of intracranial hypertension associated with glycylcyclines: a FAERS-based disproportionality analysis 基于FAERS数据库的不成比例性分析：未发现甘氨酰环素类与颅内高压相关的药物警戒信号 Slobodan M Jankovic and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf395, https://doi.org/10.1093/jac/dkaf395 16 Posaconazole enteral tube administration in adults: pharmacokinetic target attainment of oral suspension compared with crushed delayed-release tablet 成人经肠内营养管给予泊沙康唑：口服混悬液与碾碎的缓释片的药代动力学目标达成情况比较 Nirjan Bhattarai and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf396, https://doi.org/10.1093/jac/dkaf396 17 Characterizing CYP3A4-mediated drug interactions: a fixed-sequence pharmacokinetic Chinese study of posaconazole and ruxolitinib in haematological malignancies CYP3A4介导的药物相互作用特征：一项关于泊沙康唑和鲁索替尼在血液系统恶性肿瘤中的固定序列药代动力学中国研究 Beibei Liang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf398, https://doi.org/10.1093/jac/dkaf398 18 Differences in prescription for impetigo and cellulitis across years in three European countries 三个欧洲国家不同年份脓疱病和蜂窝织炎的处方差异 Thomas Bettuzzi and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf400, https://doi.org/10.1093/jac/dkaf400 19 β-Lactam concentrations monitored in the early phase of community-acquired sepsis in the intensive care unit 重症监护室社区获得性脓毒症早期阶段监测的β-内酰胺浓度 Karolina Liljedahl Prytz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf401, https://doi.org/10.1093/jac/dkaf401 20 Enhanced antimycobacterial efficacy of simulated inhaled clofazimine versus oral clofazimine in combination with azithromycin and ethambutol in a hollow-fiber system 在空心纤维系统中，模拟吸入氯法齐明与口服氯法齐明联合阿奇霉素和乙胺丁醇的抗结核分枝杆菌疗效增强比较 Jelmer Raaijmakers and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf402, https://doi.org/10.1093/jac/dkaf402 21 Identification of antimicrobial resistance genes in Escherichia coli through network diffusion 通过网络扩散法鉴定大肠杆菌中的抗生素耐药基因 Anis Mansouri and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf404, https://doi.org/10.1093/jac/dkaf404 22 Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease 依培硼罗在脓肿分枝杆菌肺病空心纤维系统模型中的临床前评估 Sanjay Singh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf405, https://doi.org/10.1093/jac/dkaf405 23 The β-lactamase inhibitor concentration-dependent minimum inhibitory concentration (MICcBLI) as methodology to assess the pharmacokinetic/pharmacodynamic relationship of piperacillin/tazobactam for dosing optimization β-内酰胺酶抑制剂浓度依赖性最低抑菌浓度（MICcBLI）作为评估哌拉西林/他唑巴坦药代动力学/药效动力学关系以优化给药的方法 Malin Andersson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf406, https://doi.org/10.1093/jac/dkaf406 24 Unravelling the triad of penicillin-binding proteins, β-lactamase activity, and mRNA dynamics in Pseudomonas aeruginosa AmpC induction 解析铜绿假单胞菌AmpC诱导过程中青霉素结合蛋白、β-内酰胺酶活性和mRNA动态的三元关系 Maria Montaner and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf408, https://doi.org/10.1093/jac/dkaf408 25 Unnoticed spread of linear VanA-plasmids in vancomycin-variable Enterococcus faecium strains across different regions: a diagnostics challenge 不同地区万古霉素可变型粪肠球菌菌株中线性VanA质粒的未被察觉的传播：一项诊断挑战 Ana C Almeida-Santos and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf409, https://doi.org/10.1093/jac/dkaf409 26 Switching from etravirine to doravirine in virologically suppressed people with HIV: results from the French multicentre SWEED observational study 在病毒学抑制的HIV感染者中从依曲韦林切换至多拉韦林：法国多中心SWEED观察性研究的结果 Romain Palich and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf410, https://doi.org/10.1093/jac/dkaf410 27 HIV-1 drug resistance among pregnant and breastfeeding mothers and its association with paediatric HIV infections in the Dolutegravir era in Uganda 乌干达多替拉韦时代孕产妇及哺乳期母亲中HIV-1耐药情况及其与儿童HIV感染的关联 Anne Kapaata and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf411, https://doi.org/10.1093/jac/dkaf411 28 Outpatient antibiotic prescribing for medically attended respiratory syncytial virus, influenza, or human metapneumovirus illness among high-risk adults in rural Wisconsin, United States 美国威斯康星州农村地区高风险成人因呼吸道合胞病毒、流感或人偏肺病毒感染就诊时的门诊抗生素处方情况 Sarah C J Jorgensen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf412, https://doi.org/10.1093/jac/dkaf412 29 Omadacycline as a drug candidate for Mycobacterium avium infections: in vitro insights on single and combination therapies 奥马环素作为鸟分枝杆菌感染候选药物：单药及联合治疗的体外研究 Saskia E Mudde and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf413, https://doi.org/10.1093/jac/dkaf413 30 Post-pandemic trends in Streptococcus pneumoniae serotype epidemiology and antibiotic susceptibility in adults with invasive and non-invasive pneumococcal disease in the USA (2022–2023) 后疫情时代美国成人侵袭性与非侵袭性肺炎链球菌病血清型流行病学及抗生素敏感性趋势（2022-2023） Mekki F Bensaci and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf414, https://doi.org/10.1093/jac/dkaf414 31 Benznidazole pharmacokinetics in patients with chronic Chagas disease: association with demographic factors and adverse drug reactions 慢性恰加斯病患者苯芴醇药代动力学：与人口统计学因素及药物不良反应的关联 Gabriel P E Silveira and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf416, https://doi.org/10.1093/jac/dkaf416 32 Acquired antimicrobial resistance genes in Bordetella Species: a global genomic analysis 博德特氏菌属中获得的抗菌药物耐药基因：全球基因组分析 Biao Tang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf418, https://doi.org/10.1093/jac/dkaf418 33 Machine learning for personalized antimicrobial susceptibility breakpoints: (Adaptive clinical breakpoint interpretation) 基于机器学习的个性化抗菌药物敏感性折点制定（自适应临床折点解释） Yinzheng Zhong and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf419, https://doi.org/10.1093/jac/dkaf419 34 Multicentre investigation of Wickerhamomyces anomalus fungemia in India: emerging resistance and mechanistic insights 印度异常威克汉姆酵母菌血症的多中心研究：新发耐药性及机制洞察 Shristi Verma and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf420, https://doi.org/10.1093/jac/dkaf420 35 Reducing aztreonam/avibactam waste: insights from Monte Carlo simulations 减少氨曲南/阿维巴坦浪费：蒙特卡洛模拟的启示 Yeleen Fromage and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf421, https://doi.org/10.1093/jac/dkaf421 36 Nanoparticle-based co-delivery of ciprofloxacin and meropenem enhances synergistic activity against multidrug-resistant hypervirulent Klebsiella pneumoniae clinical isolates 基于纳米颗粒的环丙沙星与美罗培南共递送可增强对多重耐药高毒力肺炎克雷伯菌临床分离株的协同活性 Reham Mostafa and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf422, https://doi.org/10.1093/jac/dkaf422 37 Development of population pharmacokinetic models of total and free piperacillin in critically ill children and young adults for Monte Carlo simulations and model-informed precision dosing 危重症儿童及青年总游离哌拉西林群体药代动力学模型开发：用于蒙特卡洛模拟及模型引导的精准给药 Sonya Tang Girdwood and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf423, https://doi.org/10.1093/jac/dkaf423 38 Reaching the target: time and dose required to achieve target vancomycin plasma concentrations in admitted patients 达标分析：住院患者达到目标万古霉素血浆浓度所需的时间与剂量 W Töpfer and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf424, https://doi.org/10.1093/jac/dkaf424 39 Notable transmitted HIV drug resistance among people who inject drugs in Pakistan 巴基斯坦注射毒品人群中显著传播的HIV耐药性 Stephanie Melnychuk and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf425, https://doi.org/10.1093/jac/dkaf425 40 Synergistic but clinically unattainable: amoxicillin/ceftriaxone combination against ampicillin-susceptible Enterococcus faecium 协同但临床难以实现：阿莫西林/头孢曲松联合对氨苄西林敏感粪肠球菌的体外活性 Ahmed Ashrin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf426, https://doi.org/10.1093/jac/dkaf426 41 Pharmacodynamic studies of taniborbactam (VNRX-5133) combined with cefepime against β-lactamase–producing Gram-negative bacteria in a neutropenic murine thigh infection model 中性粒细胞减少小鼠大腿感染模型中他尼硼巴坦（VNRX-5133）联合头孢吡肟对产β-内酰胺酶革兰氏阴性菌的药效动力学研究 Panagiota-Christina Georgiou and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf431, https://doi.org/10.1093/jac/dkaf431 42 Epidemiology and treatment of endocarditis secondary to Enterobacterales other than Serratia spp. 非塞拉蒂亚属肠杆菌目细菌所致心内膜炎的流行病学及治疗 Clayton F Hausberger and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf432, https://doi.org/10.1093/jac/dkaf432 43 Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus 阿普拉霉素及其组合对脓肿分枝杆菌的增强活性 Yanqin Huang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf433, https://doi.org/10.1093/jac/dkaf433 44 Efflux-mediated multidrug resistance mechanism in Trichophyton indotineae and Trichophyton rubrum; role of ABC transporters and MFS gene 印度毛癣菌与红色毛癣菌中由ABC转运蛋白和MFS基因介导的流出泵型多重耐药机制 Dipika Shaw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf434, https://doi.org/10.1093/jac/dkaf434 45 Sphingobacterium spp. as intrinsic producers of SPI Ambler class B metallo-β-lactamases 鞘氨醇杆菌属作为SPI Ambler B类金属β-内酰胺酶的固有产生者 Delphine Girlich and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf436, https://doi.org/10.1093/jac/dkaf436 46 Global phylogeography and genomic characterization of blaNDM-1-positive carbapenem-resistant Acinetobacter soli blaNDM-1阳性碳青霉烯耐药溶胶阿卡净菌的全球系统发育地理学及基因组特征 Pengpeng Min and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf437, https://doi.org/10.1093/jac/dkaf437 47 Pharmacokinetics and tolerability of one-month daily rifapentine for latent tuberculosis treatment in haemodialysis patients 血液透析患者潜伏性结核治疗中每月一次每日利福喷丁的药代动力学及耐受性 Thornthun Ueaphongsukkit and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf439, https://doi.org/10.1093/jac/dkaf439 48 In vitro susceptibility of cefepime-enmetazobactam, cefepime-taniborbactam and cefepime-zidebactam towards carbapenemase-producing Enterobacterales 头孢吡肟-恩美他唑巴坦、头孢吡肟-他尼硼巴坦及头孢吡肟-齐德巴坦对产碳青霉烯酶肠杆菌目的体外敏感性 Marion Dutkiewicz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf440, https://doi.org/10.1093/jac/dkaf440 49 In vitro efficacy of sulbactam/durlobactam combined with β-lactam antibiotics in Australian Mycobacterium abscessus isolates 舒巴坦/杜洛巴坦联合β-内酰胺类抗生素对澳大利亚脓肿分枝杆菌分离株的体外疗效 Kirby Patterson-Fahy and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf441, https://doi.org/10.1093/jac/dkaf441 50 Harnessing CRISPR–Cas9 and CRISPRi systems to reverse antibiotic resistance in a clinical multidrug-resistant Escherichia coli isolate 利用CRISPR-Cas9及CRISPRi系统逆转临床多重耐药大肠杆菌分离株的抗生素耐药性 Ruonan Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf442, https://doi.org/10.1093/jac/dkaf442 51 Cotrimoxazole in the intensive care unit: an impossible task for the fixed association in real life? 重症监护室中复方磺胺甲噁唑的应用：固定组合在现实中的不可行性？ Manon Launay and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf443, https://doi.org/10.1093/jac/dkaf443 52 National representative survey of pretreatment HIV drug resistance in Colombia: analysis of antiretroviral resistance-associated mutations using next-generation sequencing 哥伦比亚全国代表性调查：基于下一代测序的抗逆转录病毒耐药相关突变分析 Ernesto Martínez-Buitrago and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf444, https://doi.org/10.1093/jac/dkaf444 53 A model-based comparison of dose reduction strategies for fixed-dose dolutegravir-containing regimens 基于模型的含固定剂量多替拉韦方案减量策略比较 Laura Dickinson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf445, https://doi.org/10.1093/jac/dkaf445 54 Therapeutic drug monitoring and target attainment of unbound flucloxacillin in hospitalized patients with measured MICs (FLUTE) 住院患者中游离氟氯西林的治疗药物监测及目标达成情况（基于实测最低抑菌浓度的FLUTE研究） Pjotr P Temme and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf447, https://doi.org/10.1093/jac/dkaf447 55 Nirmatrelvir-ritonavir addition to acute care formulary: a retrospective, multi-centre evaluation of quantitative economic and qualitative clinical outcomes 奈玛特韦/利托那韦纳入急症治疗目录：一项多中心回顾性评估定量经济与定性临床结果的研究 Jose Valdes Ledesma and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf448, https://doi.org/10.1093/jac/dkaf448 56 Local antibiotic resistance surveillance in nursing homes using lot quality assurance sampling: a feasibility study 采用批量质量保证抽样法对养老院进行本地抗生素耐药性监测的可行性研究 Sacha Kuil and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf451, https://doi.org/10.1093/jac/dkaf451 57 High in vitro activity of the novel antimicrobial gepotidacin against Neisseria gonorrhoeae isolates in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme countries in three WHO regions, 2021–24 2021-2024年，在世卫组织三个区域的八个世卫组织增强淋球菌抗菌药物监测计划国家中，新型抗菌药物吉皮达星对淋病奈瑟菌分离株的体外活性较高 Josefine Ahlstrand and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf452, https://doi.org/10.1093/jac/dkaf452 58 Despite increasing use of integrase inhibitors to treat HIV infection, resistance to this class remains stable 尽管整合酶抑制剂用于治疗HIV感染的使用量不断增加，但此类药物的耐药性仍保持稳定 Cathia Soulie and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf454, https://doi.org/10.1093/jac/dkaf454 59 Fine-needle aspiration in infected necrotizing pancreatitis in the delayed intervention era: a post hoc analysis of safety, microbiological yield and therapeutic implications 延迟干预时代感染性坏死性胰腺炎的细针穿刺抽吸术：安全性、微生物学检出率及治疗意义的事后分析 Hannah S Pauw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf455, https://doi.org/10.1093/jac/dkaf455 60 β-Lactam dosing in critically ill children: predictors for target non-attainment 危重症儿童β-内酰胺类药物给药：未达目标浓度的预测因素 Stef Schouwenburg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf457, https://doi.org/10.1093/jac/dkaf457 61 Co-administration of triazoles with calcineurin or mammalian target of rapamycin inhibitors in solid organ transplant patients hospitalized with invasive aspergillosis 实体器官移植患者合并侵袭性曲霉病住院时三唑类药物与钙调磷酸酶抑制剂或哺乳动物雷帕霉素靶蛋白抑制剂的联合用药情况 Barbara Alexander and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf461, https://doi.org/10.1093/jac/dkaf461 62 In vitro selection of cefiderocol-resistant mutants in Acinetobacter baumannii harbouring the most common carbapenemase genes 携带最常见碳青霉烯酶基因的鲍曼不动杆菌中头孢地尔耐药突变体的体外筛选 Otávio Hallal Ferreira Raro and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf462, https://doi.org/10.1093/jac/dkaf462 63 Preventing resistance development in infections by OXA β-lactamase-producing Pseudomonas aeruginosa: correlating clinical outcomes with hollow-fibre model input 预防产OXA β-内酰胺酶铜绿假单胞菌感染耐药性的产生：将临床结局与中空纤维模型输入相关联 María M Montero and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf464, https://doi.org/10.1093/jac/dkaf464 64 A national pilot community pharmacy–led urinary tract infection service: clinical and patient-reported outcomes from 9077 consultations 全国社区药房主导的尿路感染服务试点项目：9077次咨询的临床结局和患者报告结局 Efi Mantzourani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf466, https://doi.org/10.1093/jac/dkaf466 65 Towards enhanced translational value: preclinical drug activity testing against actively multiplying, nutrient-starved and pellicle biofilm-embedded Mycobacterium abscessus 提高转化价值：针对活跃增殖、营养匮乏和生物膜包裹的脓肿分枝杆菌进行临床前药物活性测试 Henriëtte M Meliefste and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf468, https://doi.org/10.1093/jac/dkaf468 Research Letters（研究快报） 66 Novel multiresistance transposon Tn7731 in bovine Pasteurella multocida from Germany 德国牛源多杀性巴氏杆菌中新型多重耐药转座子Tn7731 Henrike Krüger-Haker and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf336, https://doi.org/10.1093/jac/dkaf336 67 Efficacy of eravacycline in difficult-to-treat (DTR) Acinetobacter baumannii bacteraemia in ICU: a case report 厄他培南治疗重症监护病房难治性鲍曼不动杆菌菌血症的疗效：一例病例报告 Monica Melchio and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf347, https://doi.org/10.1093/jac/dkaf347 68 Possible increased risk of Epstein–Barr virus (EBV) infection and post-transplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients 来特莫韦暴露的造血细胞移植受者中EB病毒感染和移植后淋巴增殖性疾病风险可能增加 Jose F Camargo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf348, https://doi.org/10.1093/jac/dkaf348 69 Dalbavancin dosing in a severely underweight woman with prosthetic valve endocarditis: the critical role of proactive therapeutic drug monitoring 达巴万星在严重体重不足人工瓣膜心内膜炎女性患者中的给药：主动治疗药物监测的关键作用 Ambra Barco and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf365, https://doi.org/10.1093/jac/dkaf365 70 Cefazolin-induced seizures in a haemodialysis patient with elevated serum and cerebrospinal fluid concentrations: a case report 血液透析患者头孢唑林血清和脑脊液浓度升高诱发癫痫：一例病例报告 Kohei Hasegawa and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf373, https://doi.org/10.1093/jac/dkaf373 71 Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes 使用聚丙烯腈膜进行连续性肾脏替代治疗的患者中卡泊芬净药代动力学治疗监测的回顾性分析 Antoine Hérault and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf390, https://doi.org/10.1093/jac/dkaf390 72 Diffusion of OXA-48- and NDM-5-producing Klebsiella pneumoniae ST383 clone in Central Italy 产OXA-48和NDM-5的肺炎克雷伯菌ST383克隆在意大利中部的传播 Gloria D’Achille and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf397, https://doi.org/10.1093/jac/dkaf397 73 Durability of lenacapavir in viremic heavily treatment-experienced people with HIV: real-world data from the PRESTIGIO Registry 来那卡帕韦在病毒载量阳性且接受过大量抗逆转录病毒治疗的HIV感染者中的持久性：来自PRESTIGIO登记处的现实数据 Tommaso Clemente and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf415, https://doi.org/10.1093/jac/dkaf415 74 Co-carriage of the oxazolidinone resistance genes cfr and optrA in a linezolid-resistant Staphylococcus rostri isolate from a pig-farm worker 猪场工人利奈唑胺耐药猪鼻支原体分离株中噁唑烷酮类耐药基因cfr和optrA的共携带情况 Gi Yong Lee and Soo-Jin Yang Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf428, https://doi.org/10.1093/jac/dkaf428 75 Importance of reviewing the package insert from gradient strip manufacturers 梯度扩散法药敏纸片生产商说明书审阅的重要性 Mandy Wootton and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf429, https://doi.org/10.1093/jac/dkaf429 76 One resistance gene, many transposons: repeated formation of compound and pseudo-compound transposons carrying the aphA1 kanamycin and neomycin resistance gene 一个耐药基因，多个转座子：携带aphA1卡那霉素和新霉素耐药基因的复合及假复合转座子的重复形成 Christopher J Harmer and Ruth M Hall Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf450, https://doi.org/10.1093/jac/dkaf450 77 Absence of lymphogranuloma venereum among men who have sex with men on PrEP receiving doxycycline postexposure prophylaxis 接受暴露后多西环素预防性治疗的暴露前预防用药男男性行为者中未发现性病淋巴肉芽肿 Cristina Gómez-Ayerbe and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf456, https://doi.org/10.1093/jac/dkaf456 78 In vitro activity of gepotidacin against Chlamydia trachomatis 吉皮达星对沙眼衣原体的体外活性 Arabella Touati and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 1, January 2026, dkaf460, https://doi.org/10.1093/jac/dkaf460 Journal of Antimicrobial Chemotherapy Volume 81, Issue 2抗菌化疗杂志 81卷 2期 https://academic.oup.com/jac/issue Viewpoints（观点） 1 Long-acting glycopeptides: what are the barriers to access in patients who need them most, and how can they be overcome? 长效糖肽类：最需要它们的患者获取药物的障碍有哪些，如何克服？ Aleece MacPhail and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf471, https://doi.org/10.1093/jac/dkaf471 2 Redefining antifungal prophylaxis in acute leukaemia in the era of targeted therapies 靶向治疗时代急性白血病抗真菌预防的重新定义 Marcio Nucci and Johan Maertens Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag010, https://doi.org/10.1093/jac/dkag010 Reviews（综述） 3 Research progress on resistance mechanisms and clinical efficacy of tigecycline against Klebsiella pneumoniae 替加环素对肺炎克雷伯菌的耐药机制及临床疗效研究进展 Meilin Wu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf504, https://doi.org/10.1093/jac/dkaf504 4 Liposomal amphotericin B and renal safety: review of the evidence and clinical considerations 两性霉素B脂质体与肾脏安全性：证据回顾及临床考量 Johan Maertens and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf473, https://doi.org/10.1093/jac/dkaf473 5 Strategies for mitigating severe COVID-19 in patients with haematological malignancy during the omicron era 奥密克戎时代减轻血液系统恶性肿瘤患者严重新冠肺炎的策略 Keiji Okinaka and Joshua T Schiffer Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf489, https://doi.org/10.1093/jac/dkaf489 Systematic Reviews（系统综述） 6 Safety and efficacy of gepotidacin in urinary tract infection: a GRADE-assessed systematic review and meta-analysis 吉泊替达辛治疗尿路感染的安全性和有效性：一项基于GRADE评估的系统综述和荟萃分析 Taha Ibrahim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf469, https://doi.org/10.1093/jac/dkaf469 7 The emerging clinical relevance and antimicrobial resistance of Pluralibacter gergoviae: a systematic review 产吲哚金黄杆菌日益凸显的临床相关性和抗菌药物耐药性：一项系统综述 Bruna Abdul Ahad Saad and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf476, https://doi.org/10.1093/jac/dkaf476 8 A comprehensive analysis of the mutational landscape determining polymyxin resistance in Klebsiella pneumoniae 决定肺炎克雷伯菌多粘菌素耐药性的突变谱综合分析 Sambit Kumar Dwibedy and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf503, https://doi.org/10.1093/jac/dkaf503 9 Factors promoting or hindering self-administered outpatient parenteral antimicrobial therapy: a systematic literature review 促进或阻碍自我给药门诊静脉注射抗菌药物治疗的因素：一项系统文献综述 Hester H Stoorvogel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf490, https://doi.org/10.1093/jac/dkaf490 Original Research（论著） 10 Cefepime/enmetazobactam for Gram-negative periprosthetic joint infections? A randomized porcine study on target tissue pharmacokinetics 头孢吡肟/恩美唑巴坦治疗革兰氏阴性假体周围关节感染？一项关于猪的靶组织药代动力学的随机研究 M B D Nielsen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf487, https://doi.org/10.1093/jac/dkaf487 11 Impact of extracorporeal membrane oxygenation modes on voriconazole exposure in critically ill patients 体外膜肺氧合模式对危重患者伏立康唑暴露的影响 Xinrui Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf501, https://doi.org/10.1093/jac/dkaf501 12 Model-based assessment of VRC07-523LS dosing in infants through population pharmacokinetic -pharmacodynamic modelling in adults and infants 基于模型通过成人和婴儿群体药代动力学-药效学模型评估VRC07-523LS在婴儿中的给药方案 Dustin Huynh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf449, https://doi.org/10.1093/jac/dkaf449 13 Antibiotic resistance of Pseudomonas aeruginosa strains—intracellular metabolomics analysis 铜绿假单胞菌菌株的抗生素耐药性——细胞内代谢组学分析 Karolina Anna Mielko-Niziałek and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf453, https://doi.org/10.1093/jac/dkaf453 14 In vitro activity of cefepime/zidebactam against sulbactam/durlobactam-susceptible and -resistant Acinetobacter baumannii clinical isolates 头孢吡肟/齐多巴坦对舒巴坦/杜洛巴坦敏感和耐药鲍曼不动杆菌临床分离株的体外活性 Carlo Tascini and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf467, https://doi.org/10.1093/jac/dkaf467 15 Prevalence of macrolide resistance in Mycoplasma pneumoniae in The Netherlands 荷兰肺炎支原体大环内酯类抗生素耐药性的流行情况 Patrick D J Sturm and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf475, https://doi.org/10.1093/jac/dkaf475 16 Simulated lung exposure in pneumonia patients to evaluate the antibacterial capacity and resistance suppression of clinical tigecycline regimens against carbapenem-resistant Acinetobacter baumannii 模拟肺炎患者肺部暴露情况以评估临床替加环素方案对碳青霉烯类耐药鲍曼不动杆菌的抗菌能力和耐药抑制作用 Xiaonan Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf477, https://doi.org/10.1093/jac/dkaf477 17 Enterococcus faecium harbouring vanA, optrA and cfr(D) on a linear plasmid in Canada: a CANWARD surveillance case 加拿大发现携带vanA、optrA和cfr(D)的粪肠球菌线性质粒：一项CANWARD监测病例 Melissa McCracken and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf478, https://doi.org/10.1093/jac/dkaf478 18 The effect of intrauterine exposure to aminoglycosides on neonatal hearing 宫内暴露于氨基糖苷类抗生素对新生儿听力的影响 Daniel Leshin-Carmel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf483, https://doi.org/10.1093/jac/dkaf483 19 Ceftazidime/avibactam: a potent arsenal against multidrug-resistant Pseudomonas aeruginosa-unveiling in vitro and in vivo strategies 头孢他啶/阿维巴坦：对抗多重耐药铜绿假单胞菌的有力武器——揭示体内外策略 Jiaju Zhuo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf495, https://doi.org/10.1093/jac/dkaf495 20 Comparison of disk diffusion, MIC test strip and broth microdilution for eravacycline susceptibility testing of 422 Staphylococcus aureus isolates using ChinaCAST breakpoints 采用中国CAST折点，比较422株金黄色葡萄球菌对依拉环素的纸片扩散法、最低抑菌浓度测试条法和肉汤微量稀释法的敏感性测试结果 Xinying Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf502, https://doi.org/10.1093/jac/dkaf502 21 Penetration of daptomycin in cerebrospinal fluid during pneumococcal meningitis 肺炎链球菌性脑膜炎期间达托霉素在脑脊液中的渗透情况 Pascal Chavanet and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf474, https://doi.org/10.1093/jac/dkaf474 22 Rapid molecular diagnostics for detection of extensively drug-resistant Salmonella Typhi 用于检测广泛耐药伤寒沙门菌的快速分子诊断技术 Emma L Sweeney and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf481, https://doi.org/10.1093/jac/dkaf481 23 Gender inequality and antibiotic consumption: analysis of pharmaceutical sales data from 70 countries, 2000–22 性别不平等与抗生素消费：基于2000 - 2022年70个国家药品销售数据的分析 Deepshikha Batheja and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag002, https://doi.org/10.1093/jac/dkag002 24 Real-world evaluation of isavuconazole in children with cancer 伊沙康唑在儿童癌症患者中的现实应用评估 Janine Nijhuis and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf485, https://doi.org/10.1093/jac/dkaf485 25 Assessing antimicrobial susceptibility testing guideline adherence by laboratories providing bacteriology services in Ghana: a pilot study 加纳提供细菌学服务的实验室对抗菌药物敏感性试验指南依从性的评估：一项试点研究 Joseph Elikem Efui Acolatse and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag003, https://doi.org/10.1093/jac/dkag003 26 Resistance to second-generation integrase inhibitors in people with HIV following treatment failure on dolutegravir- or bictegravir-based ART in Taiwan 台湾地区基于多替拉韦或比克替拉韦的抗逆转录病毒治疗失败后，HIV感染者对第二代整合酶抑制剂的耐药性 Guan-Jhou Chen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf488, https://doi.org/10.1093/jac/dkaf488 27 In vitro activity of gepotidacin against a challenging panel of multidrug-resistant Neisseria gonorrhoeae isolates 吉泊西汀对一组具有挑战性的多重耐药淋病奈瑟菌分离株的体外活性 Michelle Jayne Cole and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag001, https://doi.org/10.1093/jac/dkag001 28 A disproportionality analysis of adverse events associated with omadacycline based on the FDA adverse event reporting system database 基于美国食品药品监督管理局（FDA）不良事件报告系统数据库的奥马环素相关不良事件比例失衡分析 Ye-Lei Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag006, https://doi.org/10.1093/jac/dkag006 29 Weight-band-based simplification of oral allometric miltefosine dosing in paediatric patients with visceral leishmaniasis 基于体重范围的口服异速缩放米替福新给药方案在儿童内脏利什曼病患者中的简化应用 Andres Mazariegos Herrera and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag014, https://doi.org/10.1093/jac/dkag014 30 evelopment of a capability framework for antimicrobial stewardship specialist health professionals working in the NHS in England: utilizing Delphi methodology 运用德尔菲法为在英国国家医疗服务体系（NHS）中工作的抗菌药物管理专业人员制定能力框架 Ryan A Hamilton and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf438, https://doi.org/10.1093/jac/dkaf438 31 First characterization of insertions in the HIV-1 integrase-coding region from people with HIV 首次对来自艾滋病病毒感染者的HIV-1整合酶编码区插入情况进行特征分析 Nhat Quang Tu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf491, https://doi.org/10.1093/jac/dkaf491 32 Development of an impedance-based fast antimicrobial susceptibility test for Neisseria gonorrhoeae 开发一种基于阻抗的淋病奈瑟菌快速抗菌药物敏感性检测方法 Caitlin N Daniels and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf493, https://doi.org/10.1093/jac/dkaf493 33 Juvenile toxicity and developmental safety of Zintrodiazine, a novel antimalarial candidate, in Wistar rats 新型抗疟候选药物Zintrodiazine在Wistar大鼠中的幼年毒性和发育安全性研究 Hitesh A Kadu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag008, https://doi.org/10.1093/jac/dkag008 34 Do the redefined EUCAST susceptibility categories warrant adjustment of paediatric antibiotic dosages? Pragmatic physiologically based pharmacokinetic modelling of four commonly used agents 欧洲抗微生物药物敏感性试验委员会（EUCAST）重新定义的敏感性分类是否需要调整儿童抗生素剂量？——对四种常用药物的实用生理药代动力学建模研究 Marika A de Hoop-Sommen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf463, https://doi.org/10.1093/jac/dkaf463 35 Exploring the opportunity for therapeutic drug monitoring (TDM) and precision dose antimicrobials in an outpatient antimicrobial therapy (OPAT) service: a prospective observational study 门诊抗菌治疗（OPAT）服务中开展治疗药物监测（TDM）和精准剂量抗菌治疗的机遇：一项前瞻性观察研究 R C Wilson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf484, https://doi.org/10.1093/jac/dkaf484 36 Impact of sex, age and body composition on rilpivirine and cabotegravir trough concentrations in people with HIV receiving long-acting injectable antiretroviral therapy 性别、年龄和身体成分对接受长效注射用抗逆转录病毒治疗的HIV感染者利匹韦林和卡博特韦谷浓度的影响 Maria Vittoria Cossu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag024, https://doi.org/10.1093/jac/dkag024 37 Pharmacokinetics of cefiderocol during prolonged intermittent kidney replacement therapy in two patients with septic shock 头孢地尔在两例感染性休克患者长时间间歇性肾脏替代治疗期间的药代动力学 Julius J Schmidt and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf496, https://doi.org/10.1093/jac/dkaf496 38 Understanding mechanisms of reduced cefiderocol susceptibility in pvdS and fecI mutants of Pseudomonas aeruginosa 了解铜绿假单胞菌pvdS和fecI突变体对头孢地尔敏感性降低的机制 Yoshinori Yamano and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag004, https://doi.org/10.1093/jac/dkag004 39 Biomarker-informed PBPK modelling of meropenem in paediatric severe pneumonia: implications for target-site PK/PD 基于生物标志物的美罗培南在儿童重症肺炎中的生理药动学模型构建：对靶部位药代动力学/药效学的影响 Yao Liu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf500, https://doi.org/10.1093/jac/dkaf500 40 Evaluating hypoalbuminaemia thresholds associated with delayed blood sterilization among patients receiving cefazolin or antistaphylococcal penicillins for MSSA bacteraemia 评估接受头孢唑林或抗葡萄球菌青霉素治疗甲氧西林敏感金黄色葡萄球菌（MSSA）菌血症患者中，与血液延迟灭菌相关的低白蛋白血症阈值 Sunish Shah and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf498, https://doi.org/10.1093/jac/dkaf498 Research Letters（研究快讯） 41 False-negative result in fourth-generation HIV screening tests after weak detection of p24 antigen in the context of inappropriate post-exposure prophylaxis use: a case report 不当使用暴露后预防用药导致第四代HIV筛查试验p24抗原弱检出后出现假阴性结果：一例病例报告 J Kimmerlin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf459, https://doi.org/10.1093/jac/dkaf459 42 Proposal for the nomenclature of tmexCD-toprJ-like gene clusters 关于tmexCD-toprJ样基因簇命名的建议 Chengzhen Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf482, https://doi.org/10.1093/jac/dkaf482 43 IS26-mediated chromosomal integration of virulence plasmid fragments in ST2237 carbapenem-resistant Klebsiella pneumoniae IS26介导的毒力质粒片段在ST2237型碳青霉烯耐药肺炎克雷伯菌染色体中的整合 Yan Li and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag018, https://doi.org/10.1093/jac/dkag018 Letter to the Editor（致编辑的信） 44 Comment on: Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes 对“采用聚丙烯腈膜对接受连续性肾脏替代治疗的患者进行卡泊芬净药代动力学监测的回顾性分析”的评论 Gwénola Marais and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf465, https://doi.org/10.1093/jac/dkaf465 45 Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy-right-to-reply 意大利米兰地区使用多西环素暴露后预防（DoxyPEP）人群中，用于治疗细菌性传播感染的抗菌药物使用情况——回应说明 Angelo Roberto Raccagni and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkag027, https://doi.org/10.1093/jac/dkag027 ACKNOWLEDGEMENT OF REFEREES（鸣谢审稿专家） 46 Acknowledgement of Referees 鸣谢审稿专家 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf417, https://doi.org/10.1093/jac/dkaf417 CORRECTION（更正） 47 Correction to: Comment on: Antiviral effect of Evusheld in COVID-19 hospitalized patients infected with pre-Omicron or Omicron variants: a modelling analysis of the randomized DisCoVeRy trial 更正：关于Evusheld在感染奥密克戎变异株前或奥密克戎变异株的新冠住院患者中的抗病毒效果：对随机DisCoVeRy试验的建模分析的评论 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 2, February 2026, dkaf492, https://doi.org/10.1093/jac/dkaf492 Journal of Antimicrobial Chemotherapy Volume 81, Issue 3抗菌化疗杂志 81卷 3期 https://academic.oup.com/jac/issue REVIEW（综述） 1 Closing the PrEP access gap in Europe: a strategic framework for equity and innovation among difficult-to-reach populations 缩小欧洲暴露前预防获取差距：面向难以触及（PrEP）人群的公平与创新战略框架 Josep M Llibre and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag052, https://doi.org/10.1093/jac/dkag052 2 Precision dosing of systemic antifungals in adults: therapeutic drug monitoring, empiric dose optimization and barriers to implementation 成人全身性抗真菌药物的精准给药：治疗药物监测、经验性剂量优化及实施障碍 Daniel B Chastain and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag055, https://doi.org/10.1093/jac/dkag055 3 Bacterial DNA topoisomerase IV and DNA gyrase inhibitors: history of the quinolones, their clinical usage and potential alternatives for the future 细菌DNA拓扑异构酶IV和DNA旋转酶抑制剂：喹诺酮类药物的历史、临床应用及未来潜在替代方案 Daisuke Fukuda and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag054, https://doi.org/10.1093/jac/dkag054 4 Combating multidrug-resistant Klebsiella pneumoniae: current therapeutic regimens and future directions 应对多重耐药肺炎克雷伯菌：当前治疗方案与未来方向 Robiul Islam and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag064, https://doi.org/10.1093/jac/dkag064 SYSTEMATIC REVIEW（系统综述） 5 Global and regional prevalence of metallo-β-lactamases in carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis 耐碳青霉烯类鲍曼不动杆菌中金属β-内酰胺酶的全球和区域流行情况：一项系统综述和荟萃分析 Stamatis Karakonstantis and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag037, https://doi.org/10.1093/jac/dkag037 Original Research（论著） 6 The effect of oral ciprofloxacin at conventional doses on the QT interval in a tertiary outpatient setting 三级门诊常规剂量口服环丙沙星对患者QT间期的影响 Weber Liu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag020, https://doi.org/10.1093/jac/dkag020 7 Bictegravir concentrations in breastmilk of healthy, lactating women without HIV 未感染人类免疫缺陷病毒（HIV）的健康哺乳期女性乳汁中的比克替拉韦浓度 L C van der Wekken-Pas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag022, https://doi.org/10.1093/jac/dkag022 8 Management and outcomes of Stenotrophomonas maltophilia recovered from deep-site clinical specimens: a bicentric retrospective cohort study 从深部部位临床标本中分离出的嗜麦芽窄食单胞菌的治疗及转归：一项双中心回顾性队列研究 Anastasia Saade and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag021, https://doi.org/10.1093/jac/dkag021 9 Development of a risk prediction model for vancomycin-associated acute kidney injury: a multicentre retrospective study 万古霉素相关急性肾损伤风险预测模型的建立：一项多中心回顾性研究 Tomoyuki Ishigo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag012, https://doi.org/10.1093/jac/dkag012 10 Cooperation between HIV-1 integrase natural polymorphism K156N and 3′PPT mutations in dolutegravir monotherapy failure HIV-1 整合酶天然多态性 K156N 与 3′PPT 突变在多替拉韦单药治疗失败中的协同作用 Jolieke A T van Osch and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag033, https://doi.org/10.1093/jac/dkag033 11 Impact of body mass index and serum albumin levels on isavuconazole plasma concentrations in patients with haematological malignancies 体重指数和血清白蛋白水平对血液系统恶性肿瘤患者艾沙康唑血浆浓度的影响 Jie Gao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag032, https://doi.org/10.1093/jac/dkag032 12 Pharmacokinetics of cefotaxime and its metabolite desacetyl-cefotaxime to optimize dosing in critically ill children and children with sickle cell disease 用以优化危重症儿童和镰状细胞病儿童给药剂量的头孢噻肟及其代谢产物去乙酰头孢噻肟的药代动力学研究 Seef Abdalla and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag019, https://doi.org/10.1093/jac/dkag019 13 Summary of ceftriaxone-resistant Neisseria gonorrhoeae in Canada, 2017–24 2017 - 2024年加拿大头孢曲松耐药淋病奈瑟菌情况汇总 Robyn Thorington and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag007, https://doi.org/10.1093/jac/dkag007 14 Improving perioperative prophylactic antibiotic prescribing using a novel decision-support tool 使用新型决策支持工具改进围手术期预防性抗生素处方 Mark Mcintyre and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag015, https://doi.org/10.1093/jac/dkag015 15 Comparative activity of established versus new-generation β-lactams against AmpC-hyperproducing clinical isolates of Enterobacter cloacae complex and Klebsiella aerogenes: a multicentre study 针对产超广谱AmpC酶的阴沟肠杆菌复合群和产气克雷伯菌临床分离株，比较已上市与新一代β-内酰胺类抗生素的抗菌活性：一项多中心研究 Ángel Rodríguez-Villodres and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag034, https://doi.org/10.1093/jac/dkag034 16 Impact of eravacycline on fibrinogen 依拉环素对纤维蛋白原的影响 Emily Stevenson and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag030, https://doi.org/10.1093/jac/dkag030 17 Biliary pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime–avibactam in a case series of orthotopic liver transplant recipients 原位肝移植受者连续输注头孢他啶-阿维巴坦的药代动力学/药效学胆系分析：一项病例系列研究 Milo Gatti and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag009, https://doi.org/10.1093/jac/dkag009 18 Autoaggregation-associated carbapenem tolerance mediated by mrkH inactivation identified from a cohort of Klebsiella pneumoniae species complex clinical isolates 从肺炎克雷伯菌复合群临床分离株队列中鉴定出由mrkH失活介导的与自动聚集相关的碳青霉烯耐受性 Natsuki Yamanaka and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag017, https://doi.org/10.1093/jac/dkag017 19 In vitro activity of double and triple antimicrobial combinations against carbapenem-resistant Pseudomonas aeruginosa biofilm 双联和三联抗菌药物组合对碳青霉烯耐药铜绿假单胞菌生物膜的体外活性研究 Si-Ho Kim and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag031, https://doi.org/10.1093/jac/dkag031 20 LYSC98 as a novel vancomycin-derived agent effective against antibiotic-resistant pathogens in tolerant state LYSC98作为一种新型万古霉素衍生物，对耐受状态下的耐药病原体有效 Xing Xia and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag036, https://doi.org/10.1093/jac/dkag036 21 HBV status modulates transaminase decrease after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people with HIV HIV感染者从富马酸替诺福韦二吡呋酯切换为丙酚替诺福韦后，HBV状态对转氨酶下降的调节作用 Giuseppe Lapadula and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag045, https://doi.org/10.1093/jac/dkag045 22 Pharmacokinetics of colistin in adult critically ill patients in South Africa 南非成人危重症患者中多黏菌素的药代动力学研究 Veshni Pillay-Fuentes Lorente and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag011, https://doi.org/10.1093/jac/dkag011 23 Antifungal susceptibility surveillance of clinical moulds to olorofim, manogepix, amphotericin B, triazoles and echinocandins at 10 tertiary hospitals in China (2019–24) 2019 - 2024年中国10家三级医院临床霉菌对奥罗芬净、马诺盖匹克斯、两性霉素B、三唑类和棘白菌素类抗真菌药的敏感性监测 Su Chen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag016, https://doi.org/10.1093/jac/dkag016 24 Short-cycle three-day-per-week efavirenz/emtricitabine/tenofovir disoproxil fumarate therapy: a seven-year extension study 短周期每周三日依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯疗法：一项为期七年的延长研究 Beatriz Borjabad and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag040, https://doi.org/10.1093/jac/dkag040 25 Risk of hypertension in people with HIV in the USA initiating modern antiretroviral regimens: pooled analysis of blood pressure data from five clinical trials 美国感染HIV者启动现代抗逆转录病毒治疗方案后患高血压的风险：五项临床试验血压数据汇总分析 Priscilla Y Hsue and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag005, https://doi.org/10.1093/jac/dkag005 26 Real-world drug monitoring of dalbavancin using a three-dose regimen of 1500mg at days 1, 15 and 43 in bone and joint or cardiovascular infection 采用第1、15和43天各1500毫克的三剂量方案对达巴万星（Dalbavancin）在骨关节或心血管感染治疗中的实际药物监测研究 Thomas Lin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag039, https://doi.org/10.1093/jac/dkag039 27 Nationwide patterns of HIV drug resistance and high viral load in Sub-Saharan African countries 撒哈拉以南非洲国家全国范围内的HIV耐药及高病毒载量模式 Abubaker Ibrahim Elbur and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkaf497, https://doi.org/10.1093/jac/dkaf497 28 Risk factors for suboptimal target attainment of commonly used ß-lactam antibiotics in older adults: a prospective cohort study 老年人常用β-内酰胺类抗生素未达最佳治疗目标的风险因素：一项前瞻性队列研究 Arnaud De Clercq and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag048, https://doi.org/10.1093/jac/dkag048 29 Physiologically based pharmacokinetic modelling to optimize dosing regimen of biapenem in renal impairment and elderly populations 基于生理的药代动力学模型优化肾功能不全及老年人群比阿培南给药方案 Wenyan Li and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkaf499, https://doi.org/10.1093/jac/dkaf499 30 Early targeted therapy guided by rapid phenotypic antimicrobial susceptibility testing in critically ill patients with Gram-negative bacterial bloodstream infections: a retrospective cohort study 快速表型抗菌药物敏感性试验指导下的早期目标性治疗对革兰氏阴性菌血流感染危重患者的效果：一项回顾性队列研究 Salvatore Rotundo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag056, https://doi.org/10.1093/jac/dkag056 31 Impact of COVID-19-related healthcare changes on antibiotic resistance in clinical Escherichia coli isolates: interrupted time series analyses in Scotland, UK 与新冠肺炎相关的医疗变化对英国苏格兰地区临床大肠杆菌分离株抗生素耐药性的影响：中断时间序列分析 Laura Ciaccio and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag049, https://doi.org/10.1093/jac/dkag049 32 Multicentre evaluation of teicoplanin prescribing and monitoring in the UK and Ireland: the TUcK–SHOP study 英国和爱尔兰替考拉宁处方与监测的多中心评估：TUcK–SHOP研究 Stephen Hughes and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag038, https://doi.org/10.1093/jac/dkag038 33 Diabetes and risk of significant fibrosis in adults with HIV and metabolic dysfunction-associated steatotic liver disease: a prospective cohort study 糖尿病与HIV合并代谢功能障碍相关脂肪性肝病成人患者发生显著肝纤维化的风险：一项前瞻性队列研究 Win Min Han and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag053, https://doi.org/10.1093/jac/dkag053 34 A pharmacovigilance analysis of carbapenem-related utilizing the FDA adverse event reporting system (FAERS) database from 2013 to 2025 基于美国食品药品监督管理局不良事件报告系统（FAERS）数据库2013 - 2025年数据的碳青霉烯类相关药物警戒分析 Connor Frey and Parham Elmi Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag060, https://doi.org/10.1093/jac/dkag060 35 Effects of extracorporeal membrane oxygenation on the pharmacokinetics and tissue penetration rates of vancomycin and linezolid: data from Landrace pigs 体外膜肺氧合对万古霉素和利奈唑胺药代动力学及组织穿透率的影响：来自长白猪的数据 Huifang Zhang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag063, https://doi.org/10.1093/jac/dkag063 36 Switching to bictegravir/emtricitabine/tenofovir alafenamide in people with HIV and prior resistance mutations. Data from the Italian ARCA cohort: the BIC-BARRIER study. B/F/TAF switch: mutations and outcomes 在既往存在耐药突变的人类免疫缺陷病毒（HIV）感染者中换用比克替拉韦/恩曲他滨/丙酚替诺福韦治疗。来自意大利ARCA队列的数据：BIC-BARRIER研究。比克替拉韦/恩曲他滨/丙酚替诺福韦（B/F/TAF）换药方案：耐药突变与治疗结果 Laura Pezzati and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag035, https://doi.org/10.1093/jac/dkag035 37 A two-stage diagnostic model for discriminating and assessing risk of meropenem heteroresistance in Pseudomonas aeruginosa 用于鉴别和评估铜绿假单胞菌对美罗培南异质性耐药风险的二阶段诊断模型 Yali Fan and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag061, https://doi.org/10.1093/jac/dkag061 38 Microdialysis assessment of gentamicin for second-line antimicrobial prophylaxis in abdominal surgery 微透析评估庆大霉素在腹部手术中作为二线抗菌预防药物的效果 Quentin Saint-Genis and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag071, https://doi.org/10.1093/jac/dkag071 39 Genetic and clinical predictors of voriconazole pharmacokinetics and hepatotoxicity: focused on CYP2C19 normal and intermediate metabolizers 伏立康唑药代动力学及肝毒性的遗传和临床预测因素：聚焦于CYP2C19正常代谢型和中间代谢型 Hui Li and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag065, https://doi.org/10.1093/jac/dkag065 40 Stakeholder perspectives on the offer and acceptance of self-administration of outpatient parenteral antimicrobial therapy: a qualitative study 利益相关者对提供和接受门诊患者自行注射抗菌药物治疗的看法：一项定性研究 Hester H Stoorvogel and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag068, https://doi.org/10.1093/jac/dkag068 41 Is current guidance for cloxacillin prophylaxis dosages in hip and knee arthroplasty adequate? Evidence from a prospective Swedish cohort 当前髋关节和膝关节置换术中氯唑西林预防性用药剂量指南是否充分？来自一项前瞻性瑞典队列研究的证据 Katja Wallander and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag067, https://doi.org/10.1093/jac/dkag067 42 Effect of pretreatment HIV drug resistance on mortality, attrition and viral suppression in patients initiating antiretroviral therapy and genetic transmission network: an observational cohort study in Southwest China 治疗前HIV药物耐药性对开始接受抗逆转录病毒治疗患者的死亡率、失访率和病毒抑制率的影响以及遗传传播网络：中国西南地区一项观察性队列研究 Litai Qin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag073, https://doi.org/10.1093/jac/dkag073 RESEARCH LETTER（研究快讯） 43 Varicella and varicella zoster virus meningoencephalitis in a diffuse large B-cell lymphoma patient after chimeric antigen receptor-T-cell therapy 嵌合抗原受体T细胞疗法后，弥漫性大B细胞淋巴瘤患者发生水痘及水痘-带状疱疹病毒脑膜脑炎 Yan Feng and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag041, https://doi.org/10.1093/jac/dkag041 44 The ‘double hit’ on dalbavancin pharmacokinetics: hypertriglyceridaemia and augmented renal clearance in a child with glycogen storage disease type Ib 糖原累积病Ib型患儿中，高甘油三酯血症和肾清除率增加对达巴万星药代动力学的“双重打击” Bianca Monti and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag028, https://doi.org/10.1093/jac/dkag028 45 Tn7860, a novel chromosomal pseudo-compound transposon carrying the OptrA gene in Enterococcus faecalis Tn7860，粪肠球菌中携带OptrA基因的一种新型染色体假复合转座子 Francesca Romana Massacci and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag046, https://doi.org/10.1093/jac/dkag046 46 HBV reactivation after switching to cabotegravir plus rilpivirine therapy among people living with HIV: do not forget the reservoir HIV感染者换用卡博特韦（cabotegravir）联合利匹韦林（rilpivirine）治疗后乙肝病毒再激活：切勿忽视病毒储存库 Rémi Rouget and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag050, https://doi.org/10.1093/jac/dkag050 47 An inoperable mediastinal infection involving vascular graft treated with weekly oritavancin as chronic suppressive therapy. A case report with pharmacokinetic data 一例涉及血管移植物的无法手术的纵隔感染，采用每周一次的奥利万星作为慢性抑制疗法。附药代动力学数据的病例报告 Pierangelo Chinello and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag013, https://doi.org/10.1093/jac/dkag013 48 Evaluation of the Carbapenemase Detection Kit (Colloidal Gold; Macro & Micro Test): a new immunochromatographic assay for rapid detection of carbapenemases in Enterobacterales 碳青霉烯酶检测试剂盒（胶体金法；宏基因与微基因检测法）评估：一种用于快速检测肠杆菌目细菌中碳青霉烯酶的新型免疫层析法 Hippolyte De Swardt and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag066, https://doi.org/10.1093/jac/dkag066 49 Cefalexin use in UK acute pyelonephritis practice: unaddressed challenges in dosing, breakpoints and clinical evidence 头孢氨苄在英国急性肾盂肾炎治疗中的应用：给药、断点和临床证据方面尚未解决的挑战 Stephen Hughes and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag051, https://doi.org/10.1093/jac/dkag051 LETTERS TO THE EDITOR（致编辑的信） 50 Comment on: Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy 评论：意大利米兰多西环素暴露后预防（DoxyPEP）使用者中用于治疗细菌性性传播感染的抗菌药物使用情况 Chris Kenyon Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag025, https://doi.org/10.1093/jac/dkag025 51 Possible increased risk of Epstein–Barr virus (EBV) infection and post-transplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients: right-to-reply 来特莫韦暴露的造血细胞移植受者发生EB病毒（EBV）感染和移植后淋巴增殖性疾病（PTLD）的风险可能增加：答复权 Jose F Camargo and Anthony D Anderson Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag043, https://doi.org/10.1093/jac/dkag043 52 Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis (DoxyPEP) users in Milan, Italy—right-to-reply 意大利米兰市使用多西环素暴露后预防（DoxyPEP）人群中，用于治疗细菌性性传播感染的抗菌药物使用情况——答复权声明 Angelo Roberto Raccagni and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag026, https://doi.org/10.1093/jac/dkag026 53 Comment on: Artificial intelligence for improving decision-making in bacterial infection management 述评：人工智能在细菌感染管理决策中的优化作用 Daniele Roberto Giacobbe Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag078, https://doi.org/10.1093/jac/dkag078 CORRECTION（更正） 54 Correction to: Bayesian estimation of the prevalence of antimicrobial resistance: a mathematical modelling study 更正：抗菌药物耐药性流行率的贝叶斯估计：一项数学建模研究 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkaf494, https://doi.org/10.1093/jac/dkaf494 55 Correction to: National representative survey of pretreatment HIV drug resistance in Colombia: analysis of antiretroviral resistance-associated mutations using next-generation sequencing 更正：哥伦比亚具有全国代表性的治疗前HIV耐药性调查：使用下一代测序技术分析抗逆转录病毒耐药相关突变 Journal of Antimicrobial Chemotherapy, Volume 81, Issue 3, March 2026, dkag057, https://doi.org/10.1093/jac/dkag057 Journal of Antimicrobial Chemotherapy Volume 81, Issue 4抗菌化疗杂志81卷 4期 https://academic.oup.com/jac/issue 50TH ANNIVERSARY COLLECTION（50周年纪念合集） GARROD LECTURE（加罗德讲座） 1 Garrod lecture: achieving the UNGA AMR mortality reduction goals 加罗德讲座：实现联合国大会抗菌药物耐药性死亡率降低目标 Ramanan Laxminarayan Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag082, https://doi.org/10.1093/jac/dkag082 REVIEW（综述） 2 25 years of improvement in mortality in invasive aspergillosis in haematology patients: will it be sustained or is it under threat? 侵袭性曲霉病血液病患者25年死亡率改善情况：这种改善能否持续，还是正受到威胁？ Johan A Maertens and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag077, https://doi.org/10.1093/jac/dkag077 3 A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 2: from molecule to confirmed hit 针对锥虫病的从高质量潜在客户和药物开发候选者出发的战略发现路线图。第二部分：从分子到确证活性分子 Sarah Hendrickx and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag110, https://doi.org/10.1093/jac/dkag110 VIRTUAL ROUNDTABLE（虚拟圆桌会议） 4 Diagnosis and risk factors for invasive mould disease—a round table discussion on directing antifungal therapy according to the available evidence 侵袭性霉菌病的诊断与危险因素——根据现有证据指导抗真菌治疗的圆桌讨论 Ana Alastruey-Izqueirdo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag062, https://doi.org/10.1093/jac/dkag062 EDITORIALS, MESSAGES FROM THE OUTGOING AND INCOMING EDITORS-IN-CHIEF（社论、离任与就任主编寄语） 5 Message from the incoming Editor-in-Chief of JAC 《抗菌化疗杂志》就任主编寄语 Monica A Slavin Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf479, https://doi.org/10.1093/jac/dkaf479 6 Message from the outgoing Editor-in-Chief 离任主编寄语 J Peter Donnelly Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf480, https://doi.org/10.1093/jac/dkaf480 REVIEW（综述） 7 Experimental biofilm models for pharmacokinetic and pharmacodynamic investigations: bridging in vitro, ex vivo and in vivo systems 用于药代动力学和药效学研究的实验性生物膜模型：连接体外、离体和体内系统 Stephanie Supparitsch and Markus Zeitlinger Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag091, https://doi.org/10.1093/jac/dkag091 8 Antimicrobial therapy for infected necrotizing pancreatitis: microbiology, antimicrobial resistance and pharmacokinetics 感染性坏死性胰腺炎的抗菌治疗：微生物学、抗菌药物耐药性及药代动力学 Hannah S Pauw and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag092, https://doi.org/10.1093/jac/dkag092 9 Continuous linezolid infusion: the new way to dose, the old risks to fear 持续输注利奈唑胺：新的给药方式，仍需警惕旧有风险 Daniel Muñoz-Pichuante and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag100, https://doi.org/10.1093/jac/dkag100 10 Alignment of national standard treatment guidelines with WHO AWaRe recommendations for adult primary care infectious diseases: implications for antimicrobial stewardship 将国家标准治疗指南与世卫组织（WHO）针对成人初级保健传染病的“慎用、监测、备用”（AWaRe）推荐意见相统一：对抗菌药物管理的影响 Huda Arooj and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag099, https://doi.org/10.1093/jac/dkag099 SYSTEMATIC REVIEW（系统综述） 11 Healthcare providers’ experiences in caring for MDRO carriers with a focus on the moral dimensions of care: a systematic review 医疗服务提供者护理多重耐药菌（MDRO）携带者的经历——聚焦护理中的道德维度：一项系统综述 Carlijn Damsté and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag059, https://doi.org/10.1093/jac/dkag059 12 Extrapolation of oritavancin PK/PD targets to inform therapeutic drug monitoring: a systematic review 奥利他万星药代动力学/药效学目标的外推用以指导治疗药物监测：一项系统综述 Giammarco Baiardi and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag117, https://doi.org/10.1093/jac/dkag117 ORIGINAL RESEARCH（论著） 13 Beyond plasma: defining the translation value of epithelial lining fluid exposure profiles for the treatment of pneumonia 超越血浆：明确上皮衬里液暴露谱对肺炎治疗的转化价值 Yakun Fu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf458, https://doi.org/10.1093/jac/dkaf458 14 Impact of loading dose β-lactam therapy on outcomes of KPC-producing Klebsiella pneumoniae bloodstream infections in non-ICU patients: a real world study 负荷剂量β-内酰胺类药物治疗非重症监护病房患者产KPC肺炎克雷伯菌血流感染的疗效影响：一项现实研究 Luisa Frallonardo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag087, https://doi.org/10.1093/jac/dkag087 15 Rezafungin exhibits anti-biofilm properties against fungal biofilms in vitro 雷扎芬净在体外对真菌生物膜表现出抗生物膜特性 Hafsa Abduljalil and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag058, https://doi.org/10.1093/jac/dkag058 16 Vancomycin resistance predicts increased mortality in patients with Enterococcus faecium bloodstream infections: a six-year experience at a large tertiary care Italian hospital 万古霉素耐药性可预测屎肠球菌血流感染患者死亡率增加：意大利一家大型三级医院六年来的经验 Lucia Graziani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag069, https://doi.org/10.1093/jac/dkag069 17 Fluoroquinolones and the risk of panic attacks: a systematic review and disproportionality analysis using individual case safety reports from the FDA Adverse Event Reporting System (FAERS) database 氟喹诺酮类药物与惊恐发作风险：基于美国食品药品监督管理局不良事件报告系统（FAERS）数据库中个体病例安全报告的系统综述和比例失衡分析 Keeirah Hiertika Raguram and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag083, https://doi.org/10.1093/jac/dkag083 18 Cefuroxime concentrations in facial artery musculomucosal flap, buccal submucosa, subcutaneous tissue, and plasma following bolus or continuous infusion in patients undergoing oral cancer resection: a randomized clinical microdialysis study 在接受口腔癌切除术的患者中，采用随机临床微透析研究，探究头孢呋辛在面动脉肌黏膜瓣、颊黏膜下层、皮下组织和血浆中的浓度（团注或持续输注后） Johanne Ravn Hansen and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag085, https://doi.org/10.1093/jac/dkag085 19 Infection point of care tests bridge the experience gap of antibiotic STOP decisions: clinicians versus students 感染即时检测可弥补抗生素停药决策方面的经验差距：临床医生与学生对比 Archit Singhal and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkaf486, https://doi.org/10.1093/jac/dkaf486 20 Functional analysis of a novel macrolide–lincosamide resistance gene erm(57) in Cutibacterium avidum 痤疮丙酸杆菌中一种新型大环内酯 - 林可酰胺类耐药基因erm(57)的功能分析 Juri Koizumi and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag029, https://doi.org/10.1093/jac/dkag029 21 HIV drug resistance amongst children and adolescents with viraemia in Lesotho and Tanzania: a nested analysis in the GIVE MOVE trial 莱索托和坦桑尼亚病毒血症儿童及青少年中的HIV耐药性：GIVE MOVE试验的嵌套分析 Christof Manuel Schönenberger and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag070, https://doi.org/10.1093/jac/dkag070 22 Identification and assessment of paediatric cefepime-induced neurotoxicity in a retrospective cohort of paediatric intensive care patients 在儿科重症监护患者回顾性队列中识别和评估儿科头孢吡肟诱导的神经毒性 Kathryn Pavia and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag075, https://doi.org/10.1093/jac/dkag075 23 Prioritization of adverse events related to integrase inhibitors and NNRTIs: a disproportionality analysis using data from the FAERS database 整合酶抑制剂和非核苷类逆转录酶抑制剂相关不良事件的优先级排序：基于FAERS数据库数据的比例失衡分析 Gao-yang Wang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag074, https://doi.org/10.1093/jac/dkag074 24 Clinical and immunovirological status in children, adolescents and young adults with early-life-acquired HIV: a Spanish multi-cohort analysis since 2020 自2020年以来西班牙多队列分析中，儿童、青少年及青年时期感染HIV者的临床及免疫病毒学状态 Laura Tarancon-Diez and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag079, https://doi.org/10.1093/jac/dkag079 25 Population pharmacokinetics of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation—an ASAP ECMO study 接受体外膜肺氧合治疗的危重成年患者美罗培南的群体药代动力学——一项ASAP ECMO研究 Mohd H Abdul–Aziz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag090, https://doi.org/10.1093/jac/dkag090 26 Evaluation of HIV-1 transmitted drug-resistance among subtypes circulating from 2022 to 2024 in Italy: a refined analysis through next-generation sequencing 2022年至2024年意大利流行HIV-1亚型间传播耐药性的评估：通过下一代测序技术进行的精细分析 Daniele Armenia and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag084, https://doi.org/10.1093/jac/dkag084 27 Characterization of efflux pump channel of florfenicol for resistance-enhancing variant RE-CmeABC in Campylobacter 耐药增强型变异体RE-CmeABC中氟苯尼考外排泵通道在弯曲菌中的特性研究 Hong Yao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag047, https://doi.org/10.1093/jac/dkag047 28 Genomic characterization of colistin heteroresistance in Acinetobacter baumannii: Evidence for lpxD deletion and collateral sensitivity 鲍曼不动杆菌中黏菌素异质性耐药的基因组特征：lpxD缺失及附带敏感性的证据 Banu Sancak and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag076, https://doi.org/10.1093/jac/dkag076 29 Sustaining stewardship: longitudinal evaluation of an integrated antimicrobial programme in the ICU 持续管理：重症监护室（ICU）综合抗菌药物管理项目的纵向评估 Ashmitha Thomas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag086, https://doi.org/10.1093/jac/dkag086 30 Global dissemination of optrA-mediated linezolid resistance in enterococci 利奈唑胺耐药性基因optrA介导的肠球菌在全球的传播 Jia Qi Beh and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag089, https://doi.org/10.1093/jac/dkag089 31 Predicting oral cephalosporin susceptibility in Escherichia coli blood isolates using parenteral cephalosporin susceptibility testing 利用肠外头孢菌素敏感性试验预测大肠杆菌血培养分离株对口服头孢菌素的敏感性 Tho H Pham and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag093, https://doi.org/10.1093/jac/dkag093 32 The pharmacodynamics of polymyxin B in Acinetobacter baumannii in murine thigh and lung infection models 在小鼠大腿和肺部感染模型中多粘菌素B对鲍曼不动杆菌的药效动力学研究 Sanne van den Berg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag097, https://doi.org/10.1093/jac/dkag097 33 Genomic insights into the tmexCD-toprJ: plasmid-mediated evolution, dissemination and diversity in bacterial populations 关于tmexCD-toprJ的基因组见解：质粒介导的细菌群体进化、传播与多样性 Lilan Wan and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag107, https://doi.org/10.1093/jac/dkag107 34 Baseline resistance mutations and virological response to dolutegravir in treatment-naïve patients: a multicentre NGS study 初治患者基线耐药突变与多替拉韦病毒学应答：一项多中心下一代测序（NGS）研究 Alexy Inciarte and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag080, https://doi.org/10.1093/jac/dkag080 35 Novel integrase mutations linked to genotypic DTG resistance in African non-B HIV-1 strains: the DTG RESIST study 非洲非B型HIV-1毒株中与多替拉韦（DTG）基因型耐药相关的新型整合酶突变：DTG耐药研究 Nuri Han and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag088, https://doi.org/10.1093/jac/dkag088 36 Pharmacological evaluation of an ex vivo cervicovaginal HIV prevention model 体外宫颈阴道HIV预防模型的药理学评估 Lindsey B Collins and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag103, https://doi.org/10.1093/jac/dkag103 37 The magnitude of the pharmacodynamic index for NOSO-502: pathogen clearance, emergence of resistance and human dose predictions NOSO-502药效学指数的幅度：病原体清除、耐药性出现和人体剂量预测 Sanne van den Berg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag106, https://doi.org/10.1093/jac/dkag106 38 Temocillin: a therapeutic alternative in bone and joint infections due to third generation cephalosporin-resistant Enterobacterales? 替莫西林：治疗第三代头孢菌素耐药肠杆菌目引起的骨关节感染的一种替代疗法？ Louise Piquart and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag105, https://doi.org/10.1093/jac/dkag105 39 Metallo-β-lactamase–producing Enterobacterales: cyanide-containing efflux pump inhibitors as potential dual-activity inhibitors 产金属β-内酰胺酶的肠杆菌科细菌：含氰化物的外排泵抑制剂作为潜在的双活性抑制剂 Otávio Hallal Ferreira Raro and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag122, https://doi.org/10.1093/jac/dkag122 40 Outer membrane vesicles transmit blaNDM-5 and package metallo-β-lactamases to promote antibiotic resistance in Escherichia coli 外膜囊泡传递blaNDM-5并包装金属β-内酰胺酶以促进大肠杆菌的抗生素耐药性 Ting-Yin Lu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag123, https://doi.org/10.1093/jac/dkag123 41 Characterization of a ST412-K57 colistin-resistant hypervirulent Klebsiella pneumoniae strain of chicken origin 一株鸡源ST412-K57多粘菌素耐药高毒力肺炎克雷伯菌的特征分析 Qiu Xu and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag114, https://doi.org/10.1093/jac/dkag114 42 Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study 奥罗芬明与唑类抗真菌药联合使用：2期挽救治疗研究结果 Johan Maertens and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag118, https://doi.org/10.1093/jac/dkag118 RESEARCH LETTER（研究快讯） 43 Infant HIV transmission despite maternal viral suppression: a case of post-weaning seroconversion 母体病毒得到抑制，婴儿仍发生HIV传播：一例断奶后血清转阳病例 Shadia Nakalema and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag072, https://doi.org/10.1093/jac/dkag072 44 Urinary antigen–negative Legionella pneumonia in critically ill patients: value of systematic molecular testing for optimal antimicrobial therapy 危重患者中尿抗原阴性军团菌肺炎：系统分子检测在优化抗菌治疗中的价值 Livia Foglia Manzillo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag101, https://doi.org/10.1093/jac/dkag101 45 Contribution of SHV-1 overexpression to carbapenem resistance in a Klebsiella pneumoniae clinical isolate SHV-1过表达对某株肺炎克雷伯菌临床分离株碳青霉烯类抗生素耐药性的影响 Céline Plainvert and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag108, https://doi.org/10.1093/jac/dkag108 LETTER TO THE EDITOR（致编辑的信） 46 Comment on: Possible increased risk of Epstein–Barr virus (EBV) infection and posttransplant lymphoproliferative disease (PTLD) in letermovir-exposed haematopoietic cell transplantation recipients 评论：接受莱特莫韦治疗的造血细胞移植受者中，EB病毒（EBV）感染和移植后淋巴增殖性疾病（PTLD）的风险可能增加 Jan Styczynski Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag042, https://doi.org/10.1093/jac/dkag042 47 Comment on: Antimicrobial use for the treatment of bacterial sexually transmitted infections among doxycycline post-exposure prophylaxis users in Milan, Italy 评论：意大利米兰地区使用多西环素暴露后预防措施人群中针对细菌性性传播感染的抗菌药物使用情况 Luca Bortolani and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag023, https://doi.org/10.1093/jac/dkag023 48 Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes—right to reply 使用聚丙烯腈膜进行连续肾脏替代治疗的患者中卡泊芬净药物治疗监测的回顾性分析——答复权 Antoine Hérault and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag095, https://doi.org/10.1093/jac/dkag095 49 Comment on: Temocillin versus other intravenous beta-lactams for urinary tract infections caused by third-generation cephalosporin-resistant Enterobacterales: a multicentre retrospective matched-cohort study 评论：替莫西林与其他静脉注射β-内酰胺类抗生素治疗第三代头孢菌素耐药肠杆菌目引起的尿路感染：一项多中心回顾性匹配队列研究 Shanshan Ru and Yingzhe Zhang Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag096, https://doi.org/10.1093/jac/dkag096 50 Comment on: Long-acting glycopeptides: what are the barriers to access in patients who need them most, and how can they be overcome? 评论：长效糖肽类抗生素：对于最需要它们的患者，获取的障碍是什么，如何克服？ Marco Bongiovanni Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag102, https://doi.org/10.1093/jac/dkag102 51 Comment on ‘Retrospective analysis of pharmacological therapeutic monitoring of caspofungin in patients undergoing continuous renal replacement therapy using polyacrylonitrile membranes’ 评论：“对使用聚丙烯腈膜进行连续肾脏替代治疗的患者中卡泊芬净的药理学治疗监测的回顾性分析” Julien Massol and Frédéric Baud Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag094, https://doi.org/10.1093/jac/dkag094 52 Comment on: ‘Epidemiology and treatment of endocarditis secondary to Enterobacterales other than Serratia spp’ 对“除塞拉蒂亚属（Serratia spp）外肠杆菌目所致心内膜炎的流行病学和治疗”的评论 Gianpiero Tebano and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag098, https://doi.org/10.1093/jac/dkag098 53 ‘Comparing serotype coverage of pneumococcal vaccines with PCV21 (V116), a new 21-valent conjugate pneumococcal vaccine, and the epidemiology of its eight unique Streptococcus pneumoniae serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) causing invasive pneumococcal disease in adult patients in Canada: SAVE study, 2018–2021-right-to-reply’ “比较肺炎球菌疫苗的血清型覆盖率——PCV21（V116，一种新型21价结合肺炎球菌疫苗）与加拿大成人患者中导致侵袭性肺炎球菌疾病的其8种独特肺炎链球菌血清型（15A、15C、16F、23A、23B、24F、31和35B）的流行病学：SAVE研究，2018 - 2021年——回应” John J Schellenberg and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag126, https://doi.org/10.1093/jac/dkag126 54 Comment on: Antagonistic in vitro interaction between olorofim and voriconazole against Aspergillus fumigatus 评论：奥罗芬明与伏立康唑对烟曲霉的体外拮抗作用 Corinne Pinder and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag119, https://doi.org/10.1093/jac/dkag119 55 Epidemiology and treatment of endocarditis secondary to Enterobacterales other than Serratia spp.: right-to-reply 除塞氏杆菌属外肠杆菌科细菌所致心内膜炎的流行病学和治疗：回应 Sunish Shah and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 4, April 2026, dkag121, https://doi.org/10.1093/jac/dkag121 Journal of Antimicrobial Chemotherapy Volume 81, Issue 5抗菌化疗杂志81卷 5期 https://academic.oup.com/jac/issue 50TH ANNIVERSARY COLLECTION（50周年纪念合集） REVIEW（综述） 1 A strategic discovery roadmap towards high-quality leads and drug development candidates for kinetoplastid diseases. Part 1: setting the stage 针对动基体病的高质量先导化合物及药物开发候选物的战略发现路线图。第一部分：背景介绍 Sarah Hendrickx and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag109, https://doi.org/10.1093/jac/dkag109 REVIEW（综述） 2 Pathophysiology, risk factors and clinical management for polymyxin-associated acute kidney injury 多粘菌素相关急性肾损伤的病理生理学、危险因素及临床治疗 Simiao Zhao and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag132, https://doi.org/10.1093/jac/dkag132 SYSTEMATIC REVIEW（系统综述） 3 Definitions and rates of treatment failure in females with uncomplicated urinary tract infection: a systematic literature review 女性单纯性尿路感染治疗失败的定义及发生率：一项系统文献综述 Meghan E Luck and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag112, https://doi.org/10.1093/jac/dkag112 4 Therapeutic drug monitoring and the role of pharmacokinetics/pharmacodynamics in optimizing beta-lactam antibiotic dosing for deep-seated infections: a systematic review 在针对深部感染的β-内酰胺类抗生素优化给药方案中治疗药物监测以及药代动力学/药效学的作用：一项系统综述 Cassandra Vale and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag142, https://doi.org/10.1093/jac/dkag142 ORIGINAL RESEARCH（论著） 5 Optimizing cloxacillin prophylaxis in hip and knee arthroplasty based on population pharmacokinetics of unbound plasma concentrations 基于游离血浆浓度群体药代动力学优化髋关节和膝关节置换术中的氯唑西林预防用药方案 Gustaf Beijer and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag116, https://doi.org/10.1093/jac/dkag116 6 The tissue distribution and pharmacokinetics of [14C]-olorofim following intravenous dosing in the rat 大鼠静脉注射[14C]奥洛罗芬后的组织分布及药代动力学研究 Derek Law and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag120, https://doi.org/10.1093/jac/dkag120 7 Insights from the WHO Tricycle-aligned Fleming Fund EQASIA External Quality Assessment (EQA) programme detecting ESBL-, AmpC- and carbapenemase-producing Escherichia coli in South and South-East Asia 世界卫生组织三轮车项目（Tricycle）协同的弗莱明基金南亚和东南亚地区外部质量评估（EQASIA EQA）计划在检测南亚和东南亚地区产超广谱β-内酰胺酶（ESBL）、AmpC酶和碳青霉烯酶的大肠埃希菌方面的见解 Hiba Al-Mir and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag129, https://doi.org/10.1093/jac/dkag129 8 The plasma and intracellular exposure of intramuscularly administered long-acting cabotegravir and rilpivirine in people with HIV HIV感染者肌内注射长效卡博特韦和利匹韦林后的血浆及细胞内暴露情况 Micol Ferrara and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag113, https://doi.org/10.1093/jac/dkag113 9 In vitro synergistic activity of minocycline and biapenem against cefiderocol-resistant New Delhi metallo-β-lactamase-producing Enterobacterales 米诺环素与比阿培南在体外对产新德里金属β-内酰胺酶且对头孢地尔耐药的肠杆菌科细菌的协同作用 Takashi Okanda and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag128, https://doi.org/10.1093/jac/dkag128 10 Mortality risk of ESBL producers in Escherichia coli bacteraemia: a comprehensive analysis using the PROBAC cohort 产超广谱β-内酰胺酶大肠埃希菌菌血症的死亡风险：基于PROBAC队列的综合分析 Paula Olivares-Navarro and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag130, https://doi.org/10.1093/jac/dkag130 11 Molecular mechanism of envZ regulating β-lactam antibiotic resistance and virulence in Escherichia coli EnvZ调控大肠埃希菌β-内酰胺类抗生素耐药性及毒力的分子机制 Kun Yang and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag104, https://doi.org/10.1093/jac/dkag104 12 In vitro activity of amoxicillin combined with oral cephalosporins against endocarditis-associated E. faecalis clinical isolates 阿莫西林联合口服头孢菌素针对心内膜炎相关粪肠球菌临床分离株的体外活性 David Luque Paz and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag127, https://doi.org/10.1093/jac/dkag127 13 Genome-wide association studies builds a predictive model and reveals novel resistance features for macrolide-resistant Bordetella pertussis 全基因组关联研究构建预测模型并揭示大环内酯类耐药百日咳鲍特菌的新耐药特征 Jialiang Chen and Guowei Liang Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag131, https://doi.org/10.1093/jac/dkag131 14 Real-world validation of a reduced-dose continuous infusion cefepime regimen: pharmacodynamic target attainment, efficacy and neurotoxicity 减量持续静脉输注头孢吡肟方案的实际应用验证：药效学目标达成情况、疗效及神经毒性 Kieffer Korvin and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag138, https://doi.org/10.1093/jac/dkag138 15 Cross-species and cross-border spread of aph(3′)-ia-mediated neomycin resistance in Escherichia coli from animals: a genomic perspective 从基因组角度研究动物源大肠杆菌中aph(3′)-ia介导的新霉素耐药性的跨物种和跨国传播 Mattia Pirolo and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag143, https://doi.org/10.1093/jac/dkag143 16 Prevalence of cyp51A variants in a US collection of Aspergillus fumigatus clinical isolates and comparative analysis of their contribution to triazole antifungal resistance 美国烟曲霉临床分离株集合中cyp51A变异体的流行情况及其对三唑类抗真菌药物耐药性作用的比较分析 Luisa Fernanda Gómez Londoño and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag124, https://doi.org/10.1093/jac/dkag124 17 In vitro and in vivo activity of daptomycin plus ceftaroline for the treatment of experimental endocarditis due to Enterococcus faecalis with and without high-level aminoglycoside resistance 达托霉素联合头孢洛林对高水平氨基糖苷类耐药及非耐药粪肠球菌所致实验性心内膜炎的体内外疗效研究 María-Alexandra Cañas and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag136, https://doi.org/10.1093/jac/dkag136 18 Pharmacokinetics of a three-dose regimen of intramuscular benzathine penicillin G in pregnant women with syphilis 三剂苄星青霉素G肌内注射方案在妊娠期梅毒患者中的药代动力学研究 Eshetie Melese Birru and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag145, https://doi.org/10.1093/jac/dkag145 19 Cefiderocol resistance mediated by mutation of the miniconductance mechanosensitive channel MscM in Klebsiella oxytoca 由产气克雷伯菌中微小电导机械敏感通道MscM发生突变所介导的头孢地尔耐药性 Pia Turowski and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag147, https://doi.org/10.1093/jac/dkag147 20 The veterinary clinic backyard lawn used for relief walks of hospitalized dogs is a hotspot for OXA-type carbapenemases in multiple Enterobacterales 兽医诊所后院供住院犬只散步的草坪是多种肠杆菌科细菌中OXA型碳青霉烯酶的传播热点区域 Yvonne Spahr and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag144, https://doi.org/10.1093/jac/dkag144 21 Pharmacokinetics of cefazolin in bariatric surgery patients: a preoperative perspective 头孢唑林在减肥手术患者中的药代动力学：术前视角 Alexandra Porlier and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag150, https://doi.org/10.1093/jac/dkag150 RESEARCH LETTERS（研究快讯） 22 Plasmid-encoded FRI-10 carbapenemase harboured by non-Enterobacter species isolated from a wastewater sample in Tokyo, Japan 从日本东京废水样本中分离出的非肠杆菌科物种携带质粒编码的FRI-10碳青霉烯酶 Kou Murakami and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag133, https://doi.org/10.1093/jac/dkag133 23 Synergistic activity of cefepime/enmetazobactam with meropenem, piperacillin, piperacillin/tazobactam, cefiderocol and fosfomycin against Klebsiella pneumoniae carrying blaKPC allelic variants 头孢吡肟/恩美唑巴坦与美罗培南、哌拉西林、哌拉西林/他唑巴坦、西他沙星和磷霉素针对携带blaKPC等位基因变体的肺炎克雷伯菌的协同作用 Alice Crema and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag141, https://doi.org/10.1093/jac/dkag141 24 MRSA and carbapenem-resistant Acinetobacter baumannii on the fall: successful infection prevention and control in Chilean ICUs 耐甲氧西林金黄色葡萄球菌和耐碳青霉烯类鲍曼不动杆菌数量下降：智利重症监护病房感染预防与控制的成功案例 Patricio Ross and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag146, https://doi.org/10.1093/jac/dkag146 LETTER TO THE EDITOR（致编辑的信） 25 Comment on: Model-based assessment of VRC07-523LS dosing in infants through population pharmacokinetic–pharmacodynamic modelling in adults and infants 评论：基于模型的评估VRC07-523LS在婴儿中的给药剂量——基于成人和婴儿群体药代动力学-药效学模型 Wanhua Qiu Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag139, https://doi.org/10.1093/jac/dkag139 26 Comment on: Comparing serotype coverage of pneumococcal vaccines with PCV21 (V116), a new 21-valent conjugate pneumococcal vaccine, and the epidemiology of its eight unique Streptococcus pneumoniae serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) causing invasive pneumococcal disease in adult patients in Canada: SAVE study, 2018–21 评论：比较含21种血清型的肺炎球菌疫苗PCV21（V116）（一种新型21价结合肺炎球菌疫苗）的血清型覆盖范围，以及2018 - 2021年SAVE研究中导致加拿大成年患者侵袭性肺炎球菌疾病的8种独特肺炎链球菌血清型（15A、15C、16F、23A、23B、24F、31和35B）的流行病学情况 Gokul Raj Pullagura and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag125, https://doi.org/10.1093/jac/dkag125 27 Comment on: Distinct population structure and genomic context of NarAB between broiler and human clinical Enterococcus isolates 评论：肉鸡源和人临床来源肠球菌分离株中NarAB的不同种群结构和基因组背景 Alex Wong Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag134, https://doi.org/10.1093/jac/dkag134 28 Distinct population structure and genomic context of narAB between broiler and human clinical Enterococcus isolates—authors’ response 肉鸡源和人临床来源肠球菌分离株中narAB的不同种群结构和基因组背景——作者回复 Jayanth Balakuntla and others Journal of Antimicrobial Chemotherapy, Volume 81, Issue 5, May 2026, dkag135, https://doi.org/10.1093/jac/dkag135

2026-05-12

·生物通

综述：替诺福韦、干扰素通路与黏膜免疫：对HIV感染者的影响

**摘要****背景** 抗逆转录病毒治疗（ART）能够抑制HIV的复制，保护HIV感染者（PLWH）免于发展成艾滋病。然而，尽管接受了ART治疗，许多PLWH仍会经历慢性免疫激活，这会导致过早衰老和非艾滋病相关的并发症。慢性免疫激活（CIA）的一个原因是HIV及其潜伏库的存在。然而，越来越多的证据表明，另一类药物——核苷/核苷酸逆转录酶抑制剂（NRTIs），特别是替诺福韦，可能会独立地在黏膜组织中诱导干扰素（IFN）信号通路。替诺福韦及其他NRTIs的这种驱动CIA的作用值得进一步研究，因为这些药物需要终身服用，而PLWH更容易受到炎症相关并发症的影响。**目的** 本综述综合了证据，表明替诺福韦会在多个黏膜部位（直肠、十二指肠和阴道）中促进CIA的发生，无论个体是否感染HIV。我们详细阐述了NRTIs诱导CIA的已知机制：（1）通过抑制蛋白激酶AKT来抑制白细胞介素10（IL-10）并诱导白细胞介素12（IL-12）和干扰素刺激基因（ISGs）；（2）与内源性逆转录元件的相互作用增强干扰素反应。替诺福韦还会增加肠道中具有高ISG表达的上皮细胞数量。此外，我们还讨论了NRTIs引起的慢性干扰素信号通路可能加剧HIV潜伏库的持续存在和T细胞耗竭的假设。最后，我们提出了新的治疗策略，包括减少NRTI使用的抗逆转录病毒方案和靶向免疫调节治疗，以减轻CIA并改善PLWH的临床结局。**1 HIV感染者中的慢性免疫激活** **1.1 尽管接受ART治疗仍存在持续的免疫激活** 尽管抗逆转录病毒治疗（ART）能够完全抑制病毒复制，慢性免疫激活（CIA）和炎症仍然是HIV-1感染的典型临床特征[1-5]。无论是未经治疗的还是接受ART治疗的PLWH，其免疫激活的生物标志物都持续升高，包括白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）等炎症细胞因子的水平升高，以及T细胞上的CD38和HLA-DR表达增加，还有可溶性标志物如sCD14、sCD163、C反应蛋白（CRP）和D-二聚体[2, 6-9]。值得注意的是，即使在病毒被抑制的情况下，许多PLWH的CD4+ T细胞恢复不足，免疫重建也不完全[10]。免疫激活的持续存在具有重要的临床意义，它与严重的非艾滋病事件（如神经认知障碍、冠状动脉疾病、慢性肝肾功能障碍、代谢综合征、骨质疏松症和非HIV相关癌症）的加速发生有关[1, 2, 11]。这些并发症反映了所谓的“炎症老化”现象，即PLWH在较年轻时就会出现与年龄相关的健康问题[12-15]，从而缩短了他们的健康寿命[16, 17]。在本节中，我们将简要讨论PLWH中CIA的可能原因。**1.2 慢性免疫激活的潜在机制** **1.2.1 HIV潜伏库和残留病毒的产生** HIV-1潜伏库的持续存在是CIA的一个原因[18]。潜伏感染的细胞携带整合的病毒DNA[19]。这些潜伏细胞会偶尔产生病毒核酸、蛋白质和完整的病毒颗粒，为免疫系统提供抗原刺激。HIV蛋白p17、p24和gp41可以刺激Toll样受体（TLR）-2[20]，而HIV RNA则刺激TLR-7和TLR-9[21]。糖蛋白120与CCR5结合，诱导炎症细胞因子IL-1β的产生[22]。逆转录的HIV-1 DNA被IFI16识别，进一步刺激炎症细胞因子的产生[23]。 **1.2.2 微生物移位和肠道屏障功能障碍** 治疗期间，微生物通过胃肠道移位也会导致CIA[24]。HIV会杀死肠道中的CCR5+ CD4+ T细胞，尤其是TH17细胞[26]。这些细胞的减少，加上HIV引起的炎症，会增加肠道通透性，使微生物及其成分（如脂多糖（LPS）、鞭毛蛋白和肽聚糖）进入血液，从而引发免疫激活和炎症[27-29]。慢性HIV感染者体内的LPS水平升高，并且即使在接受ART治疗后也无法完全恢复正常[24]。HIV-1感染还会改变肠道微生物群，这种变化本身也与肠道炎症、微生物移位和周围T细胞激活增加有关[30]。 **1.2.3 共感染** 与其他病原体的共感染也会加剧PLWH的CIA[31-33]。尽管接受了ART治疗，PLWH仍可能更频繁地出现潜伏病毒的再激活，如巨细胞病毒（CMV）、单纯疱疹病毒（HSV）和Epstein–Barr病毒，这些病毒反过来又会促进CIA[31-33]。同时感染丙型肝炎病毒（HCV）和HIV-1的女性表现出更高的T细胞激活水平，而HCV的治疗可以减少这种T细胞激活[34]。 **1.2.4 免疫失调** 未经治疗的HIV感染会导致多种免疫紊乱，不仅仅是CD4+ T淋巴细胞的逐渐减少。其中许多问题在开始ART治疗后也无法完全解决，尤其是在初次感染后很长时间才开始治疗的情况下。调节性T细胞（Tregs）对于平衡免疫激活至关重要[35]，但HIV感染会使其数量减少[36-40]。ART可以在一定程度上恢复Tregs的数量，但PLWH的Tregs仍保留较高的抑制性受体（如PD-1和CTLA-4）水平[40]。T细胞衰老（表现为端粒缩短、CD57上调以及共刺激分子CD28和CD27下调[41]）在HIV感染下会加速，并且即使病毒被持续抑制也会持续存在[42, 43]。此外，感染还会增加色氨酸（Trp）降解酶吲哚胺2,3-双加氧酶（IDO）的活性，这种活性在ART治疗期间可能持续存在，导致Trp代谢物犬尿氨酸（Kyn）的积累[44]。Kyn/Trp比值的升高与炎症和虚弱有关[44]。HIV感染还会导致淋巴组织纤维化，一旦形成这种变化通常是不可逆的，从而加剧免疫功能障碍[45, 46]。 **1.2.5 遗传和宿主因素** 遗传因素会影响慢性HIV感染期间的免疫激活程度[47]。例如，IL-10基因的多态性与PLWH的死亡率降低和CD4+ T细胞损失减缓有关[48, 49]。干扰素调节因子7（IRF7）基因的多态性会降低浆细胞样树突状细胞对HIV-1的IFN-α反应[50]。某些KIR-HLA基因型即使在接受有效降低病毒载量的ART治疗后也无法实现免疫恢复[51]。 **1.3 性别差异对慢性免疫激活的影响** 虽然上述机制普遍适用于PLWH，但大量文献表明生物学性别对免疫反应有影响[52]。女性通常比男性产生更强的免疫反应，基线CD4+ T细胞水平更高，抗体反应也更强烈。这些差异可能导致HIV感染中的免疫激活和临床结果存在差异[53, 54]。多项研究表明，接受抑制性ART治疗的HIV女性表现出比男性更严重的CIA[55-57]。尽管病毒被长期抑制，这些差异仍然存在，但其程度可能因人群和使用的CIA测量方法而异。例如，一项研究发现，在长期抑制性治疗下，两性之间的免疫激活差异很小[58]。了解PLWH中的性别特异性免疫差异很重要，因为免疫激活可能影响妇科健康和妊娠结果。**2 本综述的背景** 上述PLWH中CIA的机制在文献中已有详细描述。相对缺乏的是对抗逆转录病毒药物本身是否可能导致CIA的考虑。虽然ART显著减少了HIV复制和相关的免疫激活，但越来越多的证据表明，核苷/核苷酸逆转录酶抑制剂（NRTIs），如替诺福韦，可能在黏膜组织中刺激先天免疫反应，尤其是I/III型干扰素系统。以下部分将探讨NRTIs诱导的免疫激活的证据。**2.1 替诺福韦及其基于替诺福韦的PrEP在临床研究中的免疫和促炎效应** 替诺福韦是一种常用的抗逆转录病毒药物，用于治疗PLWH和预防HIV感染[59-66]。特别是，它是最常见的口服暴露前预防（PrEP）方案Truvada的组成部分，该方案包含两种NRTIs：替诺福韦二丙氧基富马酸盐（TDF）和恩曲他滨（FTC）。它也被研究作为阴道和直肠应用的局部预防剂。作为PrEP使用时，可以研究其对无HIV状态下的免疫激活的影响。在这里，我们描述了替诺福韦在黏膜中的免疫激活效应：（1）局部给药后引起的炎症和上皮屏障破坏；（2）局部和口服给药后在黏膜部位诱导的干扰素刺激基因；（3）抑制抗炎细胞因子IL-10并相应地刺激促炎细胞因子IL-12。 **2.2 阴道中的炎症和上皮屏障破坏** 两项关于局部应用替诺福韦的研究表明，该药物对阴道黏膜具有促炎和破坏屏障的作用。一项TDF阴道环的I期试验发现了意外的炎症反应。该试验将TDF阴道环与安慰剂进行比较，在分配到TDF阴道环的12名女性中有8名（67%）在8天后出现了1级阴道溃疡[67]。安慰剂组没有出现溃疡。在第14天和第28天，多种炎症细胞因子和趋化因子显著升高，IL-1α、IL-1β、TNF-α、IL-6、CXCL9、CXCL10等介质增加了5到15倍。外宫颈组织的RNA测序显示炎症通路、干扰素反应和T淋巴细胞激活增强。类似药物的局部应用也导致了阴道溃疡：一项使用1% cidofovir乳膏的临床试验中，33名PLWH中有13人出现了轻度至中度溃疡[68]。TDF阴道环导致阴道溃疡的具体机制尚不清楚。聚合物本身不太可能具有毒性，因为相同的安慰剂环没有引起溃疡。TDF在体内代谢为替诺福韦和甲醛，这些物质可能引起局部刺激[69]。毒性效应与阴道微生物群的变化无关，因为没有观察到一致的微生物群改变[67]。然而，在另一项针对相同数量参与者的研究中，虽然也使用了TDF阴道环，但没有观察到溃疡[70]。不过，那项研究仅进行了14天的测试，而实际溃疡是在平均32天后出现的，这表明黏膜损伤是逐渐累积的，可能在2周内不会引起临床可见的症状。另一个值得注意的差异是，长期研究的参与者有性活动[67]，而之前的研究是在禁欲的女性中进行的[70]。已有研究表明，性活动本身会增加青少年和年轻人的宫颈阴道免疫激活[71]，性活动引起的微损伤可能会增强药物的毒性。体外研究表明，暴露于替诺福韦或替诺福韦艾拉芬胺的初级生殖上皮细胞和成纤维细胞的伤口愈合能力受损[72]。值得注意的是，在六只无性活动的猕猴中使用该阴道环6个月后没有出现溃疡[73]，这也表明性活动可能是导致阴道环毒性的一个因素。另一种研究（MTN-014）发现局部应用替诺福韦后阴道出现免疫激活。该研究的独特交叉设计允许在同一组个体中直接比较1%替诺福韦凝胶的直肠和阴道应用效果[59]。在筛查和每次使用产品后，从阴道和直肠黏膜采集了组织样本。值得注意的是，直肠凝胶的应用不仅影响了直肠组织，还诱导了阴道组织中类似的基因表达[74]，尤其是I/III型干扰素基因的激活和与上皮-间充质转化（EMT）相关的基因上调[74]。EMT是上皮细胞获得运动性和侵袭性特征的过程，这与间充质细胞的特性相似[75]。EMT可能参与癌干细胞的生成和恶性疾病的发展[75]。虽然没有关于替诺福韦的直接研究，但在小鼠中使用NRTI阿扎硫苷进行阴道治疗时，生殖器官癌症的发生率为约25%[76]。EMT对人类皮肤的愈合也很重要：重新上皮化和伤口闭合与伤口边缘角质形成细胞中EMT相关基因的诱导有关[77, 78]。虽然没有关于阴道伤口愈合的数据，但阴道的分层鳞状上皮与表皮非常相似，只是缺乏表面角质化。因此，从推测的角度来看，替诺福韦诱导的EMT（上皮细胞迁移）过程可能是对阴道屏障破坏的反应，而不是其原因。然而，某些类型的EMT诱导与炎症有关[78, 79]，这反过来可能损害上皮细胞的完整性。2.2 I型/III型干扰素通路刺激：最一致和持久的黏膜反应I型/III型干扰素（IFN-I/III）相关基因的诱导是对替诺福韦最一致和持久的黏膜反应，无论是口服还是局部使用，在多个解剖部位都会发生，并且至少持续2个月[74, 80]。Hughes等人（2020年）证明，与每个个体的治疗前基线相比，口服TDF/FTC会在HIV未感染个体的直肠和十二指肠活检中诱导IFN刺激基因（ISGs）[80]。在直肠组织中有13个基因显著上调，其中11个属于I型干扰素通路成员：DDX60、HERC6、IFI6、IFI27、IFI27L1、IFIT1、ISG15、MX1、OAS1、RSAD2和SAMD9。Truvada诱导ISGs的现象在两个独立的直肠队列中得到了证实（Spearman r = 0.91），以及在肠道的两个部位（直肠和十二指肠，r = 0.81）。值得注意的是，TDF/FTC增加了肠道中ISG15阳性上皮细胞的数量（直肠中增加了2.76倍，p = 0.0023；十二指肠中增加了1.37倍，p = 0.06）。这些细胞中的许多同时表达了GP2，这是一种标记微褶（M）细胞的分子，这种细胞具有增强的免疫活性[81]。与治疗前相比，这些细胞频率的增加可能有助于黏膜ISG的产生[80, 82]。口服TDF/FTC诱导的相同ISGs在每天使用直肠替诺福韦凝胶7天、14天和56天后也显著富集，且随着使用时间的延长，这种富集现象更加明显[74, 80]。在每天局部使用替诺福韦14天后，阴道中也观察到了ISG基因集的富集。值得注意的是，即使参与者平均每周只使用凝胶2.9次，ISG的诱导也发生了。2.2 I型/III型干扰素通路刺激：最一致和持久的黏膜反应I型/III型干扰素（IFN-I/III）相关基因的诱导是对替诺福韦最一致和持久的黏膜反应，无论是口服还是局部使用，在多个解剖部位都会发生，并且至少持续2个月[74, 80]。Hughes等人（2020年）证明，与每个个体的治疗前基线相比，口服TDF/FTC会在HIV未感染个体的直肠和十二指肠活检中诱导IFN刺激基因（ISGs）[80]。在直肠组织中有13个基因显著上调，其中11个属于I型干扰素通路成员：DDX60、HERC6、IFI6、IFI27、IFI27L1、IFIT1、ISG15、MX1、OAS1、RSAD2和SAMD9。Truvada诱导ISGs的现象在两个独立的直肠队列中得到了证实（Spearman r = 0.91），以及在肠道的两个部位（直肠和十二指肠，r = 0.81）。值得注意的是，TDF/FTC增加了肠道中ISG15阳性上皮细胞的数量（直肠中增加了2.76倍，p = 0.0023；十二指肠中增加了1.37倍，p = 0.06）。这些细胞中的许多同时表达了GP2，这是一种标记微褶（M）细胞的分子，这种细胞具有增强的免疫活性[81]。与治疗前相比，这些细胞频率的增加可能有助于黏膜ISG的产生[80, 82]。口服TDF/FTC诱导的相同ISGs在每天使用直肠替诺福韦凝胶7天、14天和56天后也显著富集，且随着使用时间的延长，这种富集现象更加明显[74, 80]。在每天局部使用替诺福韦14天后，阴道中也观察到了ISG基因集的富集。值得注意的是，即使参与者平均每周只使用凝胶2.9次，ISG的诱导也发生了。总之，无论替诺福韦的剂型、给药途径或与FTC的联合使用方式如何，它都能一致地激活黏膜干扰素通路，这可能有助于增强黏膜的免疫反应。2.3 抑制抗炎细胞因子IL-10以及其他促炎和免疫调节效应通过人类单核细胞系和PBMC的体外研究，已经阐明了替诺福韦对细胞因子网络的影响[86-89]。Melchjorsen等人（2011年）和Murata等人（2019年）发现，替诺福韦显著降低了IL-10的产生，但增加了IL-12p70的水平，使IL-10/IL-12的平衡向更促炎的方向倾斜[86, 87]。这一体外结果在MTN-007试验中得到了体内验证，即每天在直肠应用1%的替诺福韦凝胶7天后[90]。该凝胶显著抑制了直肠黏膜中的IL-10表达，以及参与IL-10产生的两个转录因子CREB1和CREBBP的表达[91]。这种抗炎通路的抑制伴随着趋化因子CCL2、CCL19、CCL21、CXCL9和CXCL13的诱导，以及淋巴细胞标记物CD2、CD3D、CD7、CD8A和CD19水平的升高。免疫组化染色显示，直肠黏膜中浸润的T淋巴细胞（CD3+和CD7+）增加了2到5倍[91]。同样，Biswas等人证明，替诺福韦在体外处理可以刺激血液来源的巨噬细胞、树突状细胞和活化的CD4+ T细胞分泌CXCL8和CCL20[88]。在不同程度上，替诺福韦还增加了从女性生殖道分离出的CD4+ T细胞、巨噬细胞和上皮细胞分泌CXCL8、CCL20和TNF-α[89]。在体外测试小鼠细胞时，替诺福韦和一系列相关的核苷类似物刺激了促炎介质的分泌，包括CCL5、CCL3、TNF-α、IL-1β、IL-6和一氧化氮，这些介质来自分离的肝细胞、腹膜巨噬细胞和脾脏来源的淋巴细胞[92-94]。然而，一项体内小鼠研究表明，相反的结果：四种腹腔内给药的NRTIs（替诺福韦和阿德福韦）显著提高了血清中的IFN-λ3（IL-28B；一种III型干扰素）水平（中位数27.2 pg/mL），而接受核苷类似物拉米夫定或恩替卡韦的组中这一水平较低（中位数1.4 pg/mL，p < 0.001）[83]。表1列出了所有具有历史和临床重要性的核苷和核苷类似物，但作者仅测试了上述四种药物。后续的体外筛选显示，替诺福韦仅在结肠来源的上皮细胞系中诱导了IFN-λ3的表达，在肝细胞、成纤维细胞、淋巴细胞或外周血单核细胞（PBMC）中没有诱导。其他研究表明，IFN-λ受体（IFNLR1/IL-10Rβ）主要存在于上皮细胞中[84, 85]。这种组织选择性表明，口服替诺福韦特异性地在肠道上皮细胞中诱导IFN-λ3，然后从那里全身分布[83]。总之，无论替诺福韦的剂型、给药途径或与FTC的联合使用方式如何，它都能一致地激活黏膜干扰素通路，这可能有助于增强黏膜的免疫反应。2.3 抑制抗炎细胞因子IL-10及其他促炎和免疫调节效应体外研究使用人类单核细胞系和PBMC揭示了替诺福韦对细胞因子网络的影响[86-89]。Melchjorsen等人（2011年）和Murata等人（2019年）发现，替诺福韦显著降低了IL-10的产生，但增加了IL-12p70的水平，使IL-10/IL-12的平衡向更促炎的方向倾斜[86, 87]。这一体外结果在MTN-007试验中得到了体内验证，即每天在直肠应用1%的替诺福韦凝胶7天后[90]。该凝胶显著抑制了直肠黏膜中的IL-10表达，以及参与IL-10产生的两个转录因子CREB1和CREBBP的表达[91]。这种抗炎通路的抑制伴随着趋化因子CCL2、CCL19、CCL21、CXCL9和CXCL13的诱导，以及淋巴细胞标记物CD2、CD3D、CD7、CD8A和CD19水平的升高。免疫组化染色显示，直肠黏膜中浸润的T淋巴细胞（CD3+和CD7+）增加了2到5倍[91]。同样，Biswas等人证明，替诺福韦在体外处理可以刺激血液来源的巨噬细胞、树突状细胞和活化的CD4+ T细胞分泌CXCL8和CCL20[88]。在不同程度上，替诺福韦还增加了从女性生殖道分离出的CD4+ T细胞、巨噬细胞和上皮细胞分泌CXCL8、CCL20和TNF-α[89]。在体外测试小鼠细胞时，替诺福韦和一系列相关的核苷类似物刺激了促炎介质的分泌，包括CCL5、CCL3、TNF-α、IL-1β、IL-6和一氧化氮，这些介质来自分离的肝细胞、腹膜巨噬细胞和脾脏来源的淋巴细胞[92-94]。然而，一项体内小鼠研究表明，相反的结果：四种腹腔内给药的NRTIs（替诺福韦、拉米夫定和阿德福韦）减少了细菌感染引起的肝脏和全身的促炎反应，从而防止了致命的LPS休克[95]。在人体内，替诺福韦在黏膜组织中具有明显的免疫激活作用[74, 80, 91]，但在血液中的研究结果则更为矛盾[96, 97]。Castillo-Mancilla等人（2015年）记录，在健康HIV阴性成人中，使用Truvada 30天后，全身T细胞的激活显著减少，活化（CD38/HLA-DR共表达）的CD8+ T细胞从3.97%下降到2.71%（p = 0.03），并在停药30天后仍保持在2.41%[96]。相比之下，Richert-Spuhler等人（2019年）在长期使用Truvada（24-36个月）的HSV-2血清阳性女性中观察到了不同的模式[97]：外周血中的激活标志物增加，循环T细胞上的CCR5、CXCR4、CD38、Ki-67和PD-1水平升高；然而，在宫颈外观察到HIV靶细胞的可用性和免疫静息状态降低，CCR5+CD4+靶细胞的频率显著降低（PrEP期间为4%，PrEP后为8%，p = 0.0035），调节性T细胞和CD68+巨噬细胞也减少。另一方面，最近的一项研究发现，口服Truvada PrEP增加了肠道脂肪酸结合蛋白（I-FABP）的血清浓度，这是一种上皮损伤的标志物[98]。I-FABP水平与系统给药的HIV-1中和单克隆抗体的清除率呈正相关，表明黏膜损伤增加。这种对肠道黏膜的损伤可能随着时间的推移导致CIA（慢性炎症综合征）并降低同时进行的基于抗体的免疫疗法的效果。2.4 含义总之，替诺福韦无论是局部还是口服使用，都对黏膜免疫有复杂、持续时间依赖性和部位特异性的影响。I型/III型干扰素通路的刺激是替诺福韦最一致和持久的免疫学特征，无论是在所有剂型（口服TDF/FTC、局部凝胶）、给药方案（每日、宫颈周围）、黏膜部位（直肠、十二指肠、阴道）还是使用持续时间（7至56天以上）中都存在。干扰素通路的激活，结合IL-10的抑制和IL-12的诱导，是替诺福韦/Truvada使用的定义性免疫学后果。这些效应特别发生在黏膜表面，这是HIV首次侵入的地方[99-101]，可能通过增强先天免疫来提高抗病毒效果。然而，持续数月到数年的干扰素刺激可能会产生不利后果，包括促进CIA、炎症老化以及增加PLWH（艾滋病患者）的非艾滋病共病[74]。值得注意的是，大多数显示干扰素表达增加的研究是在HIV未感染个体中进行的，由于没有HIV的存在，这些个体的背景干扰素表达水平可能较低。未来的研究需要确定替诺福韦是否在PLWH中刺激I型/III型干扰素通路。此外，一致的免疫学效应仅在直接暴露于替诺福韦的黏膜部位（口服后的十二指肠和直肠，局部使用后的直肠和阴道）观察到。虽然这些变化至少可以在体外使用细胞系和PBMC中部分再现，但在体内的全身效应并不一致，或者当观察到时，可以追溯到暴露黏膜中的事件（如IFN-λ3、I-FABP）[83, 98]。这表明，全身治疗可能不会在未直接暴露于替诺福韦的组织部位（例如呼吸道或皮肤）引起类似的效果。确定次要部位是否受到影响对于评估人体免疫系统对替诺福韦和其他NRTI类药物的反应范围非常重要。3 替诺福韦和NRTIs调节干扰素系统的潜在机制替诺福韦的免疫调节作用的分子机制最近才开始被阐明。已经发现了两个关键过程：（1）AKT激酶抑制和mTOR通路调节，导致IL-10的强烈抑制[87, 102]；（2）内源性逆转录元件的抑制，导致干扰素通路激活的DNA:RNA杂合物在细胞质中的积累[103]。下面我们将更详细地描述这些过程；图1中展示了一个示意图。图1：替诺福韦对慢性免疫激活的贡献模型。步骤1：细胞摄取和代谢。口服给药后，酯前体替诺福韦二丙氧基富马酸酯（TDF）通过肠道黏膜吸收，并被上皮和血浆酯酶水解为替诺福韦（TFV）。循环中的TFV被多种细胞类型摄取，并被细胞内激酶磷酸化为活性替诺福韦二磷酸盐（TFV-DP）。TFV-DP在HIV逆转录过程中终止DNA合成，因为它缺乏与下一个核苷酸形成磷酸二酯键所需的3’-OH基团。单核细胞/巨噬细胞是LPS诱导的IL-10的主要产生者[87, 102]，因此我们推测组织巨噬细胞是介导替诺福韦对先天免疫作用的关键细胞类型。步骤2A：AKT抑制和IL-10抑制。当细菌脂多糖（LPS）与巨噬细胞上的TLR4结合时，激活了哺乳动物雷帕霉素（mTOR）通路的目标。mTOR通路的一个早期步骤是细胞质丝氨酸/苏氨酸激酶AKT的磷酸化，通过中间步骤（未显示），支持下游丝氨酸/苏氨酸激酶GSK3β的磷酸化。GSK3β的磷酸化使其在细胞质中保持失活状态，允许核内的IL-10转录因子结合并驱动IL-10基因表达。这在图2A的左侧显示，cAMP响应元件结合蛋白（CREB）代表了二十多种已知的IL-10转录因子之一[104-106]。图2A的右侧展示了当TFV与AKT结合时发生的情况，阻止了其磷酸化和下游mTOR信号传导[87, 102]。结果，GSK3β保持未磷酸化且处于活性状态，转移到细胞核并抑制IL-10转录因子的结合，从而作为IL-10转录的负调节因子。值得注意的是，类似的事件也可能在LPS以外的激活剂（如TNF-α或活细菌）刺激后发生[86]，但这方面的机制研究较少。步骤2B：逆转录元件RT抑制、cDNA:RNA杂合物积累和先天免疫感知。步骤2B已在核苷类似物拉米夫定（3TC）中得到证实，但理论上也应适用于替诺福韦[103]。NRTIs在逆转录（RT）内源性逆转录元件（包括LINE-1逆转录转座子和人类内源性逆转录病毒（HERVs）的过程中充当链终止剂[107-110]。在某些HERVs中，RNase H聚合酶活性较弱[111]，DNA链终止导致cDNA:RNA杂合物在细胞质中积累。这些杂合物被模式识别受体（cGAS、RIG-I、DDX41）识别，触发干扰素调节因子IRF3的激活[103, 112]和I型（IFN-α、IFN-β）和III型（IFN-λ3；未显示）干扰素的产生[83, 102]。步骤3：IL-10抑制和干扰素诱导。在没有替诺福韦的情况下，IL-10通过降低IRF1响应基因组的染色质可及性来抑制LPS诱导的干扰素表达，这些基因组对于I型IFN基因的转录是必需的[113]。当IL-10被替诺福韦抑制时，IRF1与I型IFN基因增强子区域的结合活性预计会增加，从而增强IFN-α/β的产生，进而刺激ISG表达（步骤4）。在巨噬细胞中，IRF1也被证明可以直接增强ISG基因的表达，无需上游干扰素的产生[114]。步骤4：干扰素系统的协同激活。I型和III型干扰素在步骤2B和3中并行产生，它们与各自的受体结合，并广泛诱导干扰素刺激基因的表达。图2（在图形查看器中打开，PowerPoint格式）。一个体外模型展示了替诺福韦增强ISG（干扰素刺激基因）的效果，以及重组IL-10对其的逆转作用。将替诺福韦（TDF）添加到脂多糖（LPS）中可以显著提高ISG15和IFI6的表达水平，超过LPS单独作用时的效果。IL-10以剂量依赖的方式逆转了这一效应。单独使用TDF没有效果（未显示）。在独立实验中测试了两位献血者（蓝色和红色），每种条件下都进行了两次细胞培养重复实验。每种条件下使用了100万个外周血单核细胞（PBMC），并在含有10%胎牛血清（FBS）、1%青霉素/链霉素和1%L-谷氨酰胺的RPMI培养基中培养。脂多糖（Invivogen，商品编号：tlrl-eblps）的浓度为100 ng/mL，替诺福韦二丙氧基富马酸盐（TDF；NIH ARP，商品编号：10198）的浓度为25 μM。重组IL-10（rIL10；Peprotech，商品编号：200–10）的浓度分别为0.1、1和10 ng/mL。细胞在37°C和5%二氧化碳（CO2）条件下与TDF和IL-10共同培养2小时，随后加入LPS培养24小时。培养26小时后，裂解细胞并提取RNA。使用High-Capacity cDNA逆转录试剂盒（ThermoFisher）制备cDNA，并通过TaqMan检测法在Naica 6色Crystal Digital PCR仪器（Bio-Rad）上定量干扰素刺激基因ISG15和IFI6。箱线图显示了中位数以及第75和第25百分位数。如果数据超出第25或第75百分位数， whiskers会延伸到相应的最小值和最大值。3.1 AKT抑制和mTOR通路调节（步骤2A）替诺福韦抑制IL-10的机制已在体外的人外周血单核细胞（PBMC）和单核细胞中得到证实。这种抑制不是通过MAPK或NF-κB信号通路实现的[86]，而是通过结合丝氨酸/苏氨酸激酶AKT来实现的[87, 102]。替诺福韦与AKT结合后，阻止了AKT从细胞质转移到细胞膜并使其磷酸化，从而阻断了下游效应因子的磷酸化以及整个PI3K/AKT/mTOR信号通路的激活[87, 102]。AKT抑制对细胞因子调节有深远影响，使平衡从抗炎性的IL-10转向促炎性的IL-12p70。AKT磷酸化并使GSK3β失活，从而解除其对IL-10表达所需转录因子的抑制作用。通过阻止AKT的磷酸化，替诺福韦使GSK3β保持活性状态，从而抑制IL-10的转录。IL-10的产生减少后，又通过抑制促炎性转录程序的机制反过来增强了IL-12p70和TNF-α的分泌[87, 102]。这种IL-10/IL-12平衡向IL-12的偏移有利于Th1反应，可能有助于病毒的清除，但从长远来看可能会导致CIA（慢性炎症老化）。值得注意的是，这种效应是NRTI（核苷酸类似物）特有的：只有替诺福韦和阿德福韦这类NRTI能够结合AKT，而核苷类似物（拉米夫定、恩替卡韦）由于缺乏关键的磷酸基团而不具备这种特性[83, 87, 102]。我们预测这种差异会导致临床上的不同免疫反应，如果得到证实，这可能会影响它们在HIV和非HIV治疗中的应用。3.2 通过IL-10抑制激活干扰素调节因子（步骤3）最近来自人类原代单核细胞的发现可能解释了替诺福韦介导的IL-10抑制与ISG（干扰素刺激基因）激活之间的联系。Mishra等人（2025年）表明，IL-10通过干扰素调节因子（IRF）类转录因子（特别是IRF1和IRF5）来抑制炎症基因的表达，而不是通过调节经典的NF-κB通路[113]。IRF1是对LPS反应的关键因素，因为它能被TLR4信号通路和自分泌的IFN-β迅速诱导，并驱动I型干扰素基因（ISGs）和炎症细胞因子的转录[113, 114]。IL-10通过减少IRF1响应基因位点处组蛋白H3第27位点的乙酰化（H3K27ac）来干扰这一过程，降低染色质的可及性[113]。因此，LPS通过IRF1诱导ISGs的表达，而IL-10直接阻断这一过程。我们推测，通过抑制IL-10，替诺福韦允许IRF1介导的ISG诱导继续进行，从而在LPS刺激下提高ISG的水平。替诺福韦增强LPS触发的ISG表达的效果以及IL-10治疗对其的逆转作用可以在体外轻易观察到（见图2）。3.3 抑制内源性逆转录元件逆转录（步骤2B）NRTI（核苷酸类似物）诱导的CIA（慢性炎症老化）的另一种机制认为，替诺福韦抑制内源性逆转录元件的逆转录，导致免疫原性核酸中间体的积累，从而触发先天免疫反应。具体来说，包括LINE-1（L1）和Alu逆转录转座子以及某些人类内源性逆转录病毒（如HERV-K）在内的逆转录元件从人类基因组转录后进行逆转录。无论是核苷酸类似物还是核苷类似物的NRTI都通过终止正在增长的核苷酸链来抑制逆转录[107-110]，导致细胞内免疫刺激性的DNA:RNA杂合体的积累。这些杂合体通过细胞质中的核酸传感器（如cGAS和RIG-I/MDA5）激活ISGs。Rajurkar等人（2022年）在结肠癌细胞中特别证明了拉米夫定（3TC）的这一机制[103]。这一机制在结肠黏膜中尤为重要，因为那里的逆转录元件非常活跃[115]，部分原因是由于暴露于高浓度的管腔LPS，这会触发逆转录元件的转录[116]。此外，L1逆转录转座子在胃肠道上皮中持续表达[117]。值得注意的是，NRTI的已知线粒体毒性[118]会导致线粒体DNA（mDNA）释放到细胞质中，为免疫原性核酸提供另一个来源[119]。步骤2A和2B可能协同作用，因为最近发现IL-10的免疫抑制活性是通过表观遗传学抑制ISG基因位点来实现的[113]。这表明，对DNA:RNA杂合体积累的ISG诱导作用因IL-10的抑制而增强。3.4 未来研究方向我们对NRTI如何导致CIA（慢性炎症老化）的理解仍有许多关键空白。需要进一步研究的问题包括：鉴于核苷酸类似物和核苷类似物都能抑制内源性逆转录元件逆转录[107-110]，但只有前者会干扰AKT/mTOR信号通路，它们在免疫学特征上是否存在差异？另一个问题是NRTI是否可能具有相反的效果。有研究小组报告称，NRTI拮抗ATP受体P2X7，从而阻断NLRP3炎性小体的激活并减少免疫刺激[120, 121]。如果得到证实，这将意味着NRTI可能同时通过干扰素和炎性小体途径表现出促炎和抗炎特性。如果是这样，那么是什么条件有利于其中一种效应的发生？此外，替诺福韦对HIV潜伏细胞的具体影响也值得探讨。Olson等人（2022年）报告称，在潜伏感染的细胞中干扰素通路受到干扰[122]。替诺福韦能否克服这种干扰？另一个值得关注的问题是，先天免疫传感器基因（如AKT、cGAS、TLR4、NLRP3）的多态性是否会影响个体对NRTI诱导的免疫激活的敏感性。最后，我们强调，虽然所描述的机制增加了替诺福韦和其他NRTI在临床应用中的合理性，但需要在HIV感染者（PLWH）中验证这一点，并评估其对CIA的贡献程度。事实上，最近有研究表明NRTI药物可能减缓HIV感染者的衰老过程[123]。显然，需要进一步的研究来明确NRTI和其他抗逆转录病毒（ART）药物对CIA和免疫老化的贡献，以便优化下一代联合治疗方案，以实现最大的抗病毒效果同时最小化免疫系统的干扰。4 HIV感染者长期ISG激活的后果HIV感染者与未感染者相比，预计健康寿命缩短16年[16, 17]。这种显著的生活质量下降表明，仅靠病毒学抑制并不能使免疫老化过程恢复正常[124]。这种炎症老化表型的一个关键因素可能是I型/III型干扰素通路的持续激活。了解持续干扰素信号的长期效应对于改进HIV治疗计划至关重要，因为减少病毒复制的药物可能会无意中维持CIA。4.1 HIV感染期间I型/III型干扰素的利与弊I型干扰素在HIV感染期间具有不同的作用。在急性感染期间，强烈的IFN-I反应可以抑制病毒复制，上调抑制因子，并启动适应性免疫。实际上，在恒河猴急性SIV感染期间阻断IFN-I信号会加速CD4细胞的耗竭并促进艾滋病的发展，这证实了IFN-I在疾病早期的保护作用[125]。然而，在慢性感染期间，持续的IFN-I信号从有益转变为有害[126, 127]。非人类灵长类动物中病原性和非病原性慢病毒感染的区别说明了这一点：SIV感染烟灰毛猴时，尽管病毒持续复制，但IFN-I反应迅速减弱，疾病不会进展。相比之下，亚洲恒河猴的SIV感染会维持较高的IFN-I反应，这被认为会促进疾病进展[128, 129]。未经治疗的HIV感染者中，病毒载量低且ISG表达低的个体疾病进展较慢[130-132]。此外，那些在没有抗逆转录病毒治疗（ART）的情况下能够维持无法检测到或极低病毒载量的精英控制者也表现出低ISG表达[132, 133]。这表明，从长远来看，ISG表达对于病毒控制可能是不必要的，但对整体健康是有害的。接受抑制性ART治疗的HIV感染者即使在血浆病毒载量无法检测到的情况下，其肠道黏膜、血液单核细胞和组织中仍常常保持较高的ISG表达[58, 126]。如第2节所述，口服替诺福韦/富马酸酯（TDF/FTC）会在整个胃肠道中诱导ISGs的表达，即使在HIV阴性的暴露前预防（PrEP）使用者中也是如此，这表明基于替诺福韦的ART可能是HIV感染者ISG持续升高的原因之一[80]。尽管目前还没有充分证据将抑制性ART治疗下的HIV感染者炎症老化直接与干扰素通路的持续激活联系起来，但持续的干扰素刺激是公认的炎症老化机制[124, 134-137]。一些直接证据表明HIV相关神经认知障碍影响了25%–50%的接受治疗的HIV感染者[138]。Tang等人（2025年）比较了接受ART治疗的HIV感染者和未感染者的脑蛋白谱：差异主要体现在免疫相关蛋白上，其中73.3%的升高蛋白与免疫相关，23.3%与IFN-I信号通路相关[139]。对大脑的单细胞RNA测序显示，即使在HIV无法检测到的情况下，星形胶质细胞、小胶质细胞和内皮细胞中也存在强烈的IFN-I活性。类似的机制也可能在其他细胞类型中起作用。长期暴露于IFN-I还会导致T细胞耗竭，表现为抑制性受体（如PD1）的上调和细胞增殖衰老[140, 141]。虽然T细胞耗竭会降低适应性免疫系统的效应功能，但它也与低水平的CIA和炎症老化相关[142-144]。在HIV感染的人源化小鼠中，尽管接受了ART治疗，CD8+和CD4+ T细胞的激活和耗竭标志物仍然升高。IFNAR阻断可以减少耗竭标志物，在HIV肽刺激下恢复IFN-γ和IL-2的产生，并降低CD4+ T细胞的激活[126, 145, 146]。4.2 慢性干扰素信号可能导致HIV病毒库的维持矛盾的是，虽然I型干扰素最初可以控制HIV复制，但在ART治疗期间持续的IFN-I信号可能会通过转录沉默整合的病毒DNA来促进病毒库的持续存在。Dickey等人（2022年）在体外实验中证明，单核细胞来源的巨噬细胞中的IFN-I产生会通过阻止NF-κB p65和RNA聚合酶II招募到HIV长末端重复序列（LTR）来促进潜伏期的形成[147]。阻断IFN-I信号可以防止潜伏期的建立，表明HIV利用自身的IFN-I诱导作用创建了转录沉默的病毒库。因此，替诺福韦可能通过诱导IFN产生来帮助维持HIV病毒库。还有证据表明，持续的高IFN信号会维持HIV病毒库。Zhen等人（2017年）和Cheng等人（2017年）使用接受含替诺福韦ART治疗的人类化小鼠证明，干扰素α/β受体（IFNAR）阻断可以减少HIV病毒库，效果优于单独使用ART[145, 146]。Deeks（2017年）预见了这些发现，指出“在ART治疗期间阻断干扰素反应可能是消除HIV病毒库的关键步骤”[148]。Swainson等人（2022年）在SIV感染的猕猴中证实了这些结果：在ART治疗期间每周注射抗IFN-α抗体可以将淋巴结中的病毒DNA减少40%（p = 0.04）[149]。然而，在两项人类研究中，单独使用IFN-α[150]或与潜伏期逆转剂联合使用[151]倾向于减少潜伏的HIV病毒库。第一项是一项小型试点试验，报告称在20周的IFN-α治疗期间外周血CD4+ T细胞中的整合DNA略有但统计上不显著的减少，但缺乏仅使用ART的对照组[150]。第二项研究评估了在ART治疗的HIV感染者中单次皮下注射IFN-α，并结合三天口服组蛋白去乙酰化抑制剂Panobinostat[151]。这种短期诱导HIV再激活和先天免疫调节的作用使HIV病毒库向转录抑制的异染色质区域倾斜。后续研究需要确定IFN-α在这种组合中的具体临床益处。这些研究为以下假设提供了一些支持：在慢性HIV感染期间，替诺福韦诱导的IFN可能会意外增加HIV病毒库的大小。也有人提出了替诺福韦基NRTIs通过其他机制促进病毒库持续存在的假设。Hladik（2015）提出替诺福韦可能通过以下方式促进潜伏：（1）直接驱动细胞增殖，包括携带HIV前病毒的细胞；（2）通过抑制IL-10来增强ISG激活和CIA，从而进一步扩大潜伏感染细胞的克隆池；（3）直接抑制整合前病毒的转录[152]，这降低了病毒库细胞对免疫系统的可见性。有三项报告通过体外潜伏模型表明NRTIs显著减少了静息T细胞中的HIV再激活[153-155]。然而，其潜在机制仍然未知。4.3 替诺福韦的贡献：加剧慢性干扰素激活？如上所述，慢性I/III型干扰素信号传导可能是HIV病毒库持续存在、T细胞耗竭、神经炎症以及接受ART治疗的PLWH（接受抗逆转录病毒治疗的HIV感染者）过早衰老和过度发病的一个被低估的驱动因素。通过刺激I/III型干扰素信号传导，基于替诺福韦的方案可能会加剧CIA[80, 83]。因此，优化ART（抗逆转录病毒治疗）方案可能是缓解CIA某些副作用的一种策略。这和其他缓解策略将在第5节中讨论。5 减少NRTI相关慢性免疫激活的治疗策略上述累积的证据表明，基于替诺福韦的NRTIs会诱导干扰素信号传导，可能同时导致CIA和HIV病毒库的持续存在。这些潜在的负面后果促使人们研究通过正常化干扰素系统的过度刺激来减少CIA的干预措施。有两种互补策略值得临床评估：（1）不使用NRTIs的抗逆转录病毒方案，以消除药物诱导的ISG激活的来源；（2）免疫调节疗法，用于阻断慢性干扰素信号传导或下游炎症途径。需要注意的是，这些策略在临床实践中应用之前需要在临床试验中进行研究。事实上，美国国立卫生研究院（NIH）艾滋病研究办公室最近发布了指南，指出仅为了减少CIA而改变ART方案或开始免疫调节疗法应仅在临床试验中进行[156]。5.1 不使用NRTIs的抗逆转录病毒方案许多非NRTI类药物已经在使用多年，但需要与NRTIs联合使用才能实现完全的病毒抑制。只有最近开发的强效整合酶链转移抑制剂（INSTIs）和新型长效制剂[157]使得无需NRTI骨架即可实现病毒抑制。口服的dolutegravir（DTG）与rilpivirine（RPV）的组合以及DTG加ritonavir增强型的darunavir在多项随机试验中显示出与含NRTIs的方案相当的效果[158-163]。长效cabotegravir加RPV代表了第一种完全不使用NRTIs的可注射ART，每月或每两个月肌肉注射一次[164-168]。此外，长效lenacapavir是一种首创的HIV-1衣壳抑制剂[169-174]，也在与bctegravir联合使用，作为一线不使用NRTIs的治疗方案进行评估[175, 176]。表2列出了目前获准临床使用的非NRTI类抗逆转录病毒药物。新的不使用NRTIs的方案在限制CIA方面的优势仍需仔细评估。临床试验应比较不使用NRTIs的方案和含替诺福韦的ART在病毒学上被抑制但具有升高炎症标志物的PLWH（接受抗逆转录病毒治疗的HIV感染者）中的效果，测量肠道黏膜ISG表达[80]、血浆IFN-λ3[83]、T细胞耗竭标志物[145, 146]、炎症生物标志物（IL-6、CRP、D-dimer、I-FABP [8, 9, 98, 177]）以及病毒库大小[178, 179]，至少持续6个月。理想情况下，应采用前瞻性、随机、交叉研究设计，将PLWH从含NRTIs的方案转换为不使用NRTIs的方案，以便每位参与者都成为自己的对照。5.2 抗逆转录病毒治疗的免疫调节辅助疗法鉴于慢性干扰素信号传导和IL-10/IL-12失衡可能促进CIA和病毒库的持续存在，针对干扰素及其相关途径的拮抗剂是合理的治疗辅助手段。几种生物制剂和小分子值得研究。Anifrolumab是一种完全人源化的单克隆抗体，可阻断IFNAR1，在狼疮试验中显示出可接受的安全性[180, 181]。Ruxolitinib是一种JAK1/2抑制剂，已被批准用于治疗骨髓纤维化、真性红细胞增多症和移植物抗宿主病[182-184]，它可以阻断IFNAR、IL-6R和其他细胞因子受体的信号传导。这两种药物都可以用来对抗PLWH中的慢性ISG诱导。实际上，在一项首创的随机临床试验中，ruxolitinib显著降低了PLWH的炎症标志物[185]。mTOR抑制剂sirolimus（雷帕霉素）和钙调神经磷酸酶抑制剂tacrolimus可以调节T细胞信号传导和代谢，用于移植[186-188]。在PLWH中的小型初步研究表明，sirolimus减少了T细胞激活，增加了中枢记忆CD4+ T细胞，并限制了IFN-I介导的炎症，尽管其临床益处仍不确定[189-193]。IL-10途径的调节提供了另一个机会。最近的研究表明，IL-10可以直接拮抗I型干扰素反应[113]。在癌症免疫治疗中测试的聚乙二醇化IL-10衍生物（pegilodecakin）理论上可以减弱IFN-I驱动的炎症[194]，但其对HIV病毒库的影响尚未得到验证。Ustekinumab是一种针对IL-12/IL-23的抗体，已被批准用于治疗银屑病和克罗恩病[195]，它可以拮抗替诺福韦对LPS诱导的IL-12诱导的增强作用[87]。然而，目前还没有数据将IL-12/23的阻断与HIV结果联系起来。事实上，在早期HIV感染期间，较高的血浆IL-12水平与较低的病毒载量和更好的CD4+ T细胞计数维持相关[196]。这一发现可能使得IL-12阻断对PLWH不利。羟氯喹可以抑制TLR9的刺激，从而机制性地抑制TLR介导的干扰素诱导和ISG表达[197]。Rother等人（2020）证明羟氯喹可以减少对病毒刺激和IFN本身的干扰素反应。一项研究已经报告羟氯喹可以减少PLWH的免疫激活[198]。来自乳酸菌的β-咔啉化合物代表了一种基于微生物组的免疫调节策略，可能对HIV预防和治疗都有潜在意义。Glick等人（2024）发现阴道中的Lactobacillus crispatus产生了一类具有强抗炎活性的β-咔啉生物碱[199]。主要化合物perlolyrine可以抑制原代人类单核细胞中的TLR介导的NF-κB和I型干扰素信号传导。有趣的是，局部阴道应用perlolyrine显著减少了小鼠HSV-2感染模型中的生殖器炎症，同时不损害上皮细胞的病毒控制[199]。这种细胞类型的特异性免疫调节，通过抑制免疫细胞中的促炎TLR/IFNAR信号传导同时保持上皮细胞的抗病毒防御，可能解决无差别干扰素阻断的一个关键问题。口服或系统给药的β-咔啉衍生物如perlolyrine可以抑制接受ART治疗的PLWH中的慢性IFNAR/TLR信号传导，可能减少病毒库的持续存在和炎症。上述免疫调节治疗可以用来对抗PLWH中的持续ISG刺激和CIA，测量指标包括病毒库的减少、免疫重建（CD4:CD8比例的恢复正常）和炎症标志物的降低。然而，这些药物应仔细监测其免疫抑制作用，特别是在长期使用时。免疫抑制可能导致并发症，如机会性感染、带状疱疹的再激活、CMV或HBV感染的加重以及活动性结核病的风险增加。为了限制副作用，这些免疫调节药物可以作为短期脉冲使用，以将干扰素系统恢复到较低的激活水平。尽管没有明确的先例，但这种策略与同时通过转换为不使用NRTIs的ART方案来减少干扰素途径刺激相结合时可能是有效的。某些药物可能比其他药物更不容易引起免疫抑制。例如，IL-10衍生物被设计为保留IL-10的理想特性，如抑制干扰素系统激活，同时消除不希望的效应，包括一般的免疫抑制[200]。天然化合物如β-咔啉衍生物存在于健康的阴道中，也可能具有抗炎作用，而不会引起危险的免疫抑制。5.3 生物性别和其他宿主因素的影响考虑性别特定的免疫反应差异至关重要[52]。性别激素[201, 202]、生殖组织中的免疫力[203]以及由于X和Y染色体导致的基因表达（如X连锁的TLR7逃逸[204]）会导致性别间的免疫反应差异。月经周期[205]、性活动[71]、怀孕、避孕、更年期和激素治疗[202]都可以调节免疫力。这包括性别确认的激素治疗。例如，在PrEP（暴露前预防）期间使用睾酮治疗可以降低宫颈FTC-TP和TFV-DP的水平[206]，这可能也会影响药物的免疫调节作用。阴道微生物组是一个独特的生态系统，其影响黏膜免疫的方式不同于肠道、皮肤或阴茎环境[207-209]。最近发现L. crispatus产生的抗炎β-咔啉可以抑制I型干扰素信号传导，突显了这一点[199]。细菌性阴道病（BV）可能会调节替诺福韦在女性生殖道中的免疫效应，因为BV相关的细菌会代谢这种药物[208]。现有的生殖器炎症，无论是由于BV还是性传播感染，也被证明会影响抗逆转录病毒药物的局部作用[210, 211]。已经发表了关于微生物组与抗逆转录病毒药物生物利用度之间关系的优秀综述[212, 213]。其他值得考虑的宿主因素包括药物生物利用度的遗传决定因素。例如，编码将替诺福韦转化为活性形式（替诺福韦二磷酸）的组织特异性激酶的基因多态性可能会影响药物活性[214]，从而可能调节其诱导CIA的效果。药物转运蛋白（如OAT1）的基因变异也可能影响替诺福韦的活性[215]，并且在不同组织中的影响可能不同[216]。类似的原则也适用于许多其他药物，其疗效和毒性受到个体间药物代谢酶和转运蛋白遗传变异的影响[217]。减轻PLWH中干扰素系统持续激活和CIA的策略应考虑许多因素，包括本节中描述的因素。6 结论总之，基于替诺福韦的ART会诱导慢性干扰素信号传导，这可能导致CIA、加速衰老和HIV病毒库的持续存在。这一发现为减少并发症提供了新的机会，并可能对HIV治愈研究具有相关性。不使用NRTIs的方案结合免疫调节剂（包括基于微生物组的β-咔啉化合物）可能代表了超越病毒抑制、朝向免疫恢复的新方向。来自黏膜免疫学、药理学、微生物组科学和干扰素研究的机制见解的融合，使得能够设计严格的试验来测试这些假设，并改善HIV感染者的治疗效果。作者声明本研究及/或文章的发表获得了财务支持。这项工作得到了美国国立卫生研究院（NIH）的以下资助：R01 AI172111、R01 AI184122、R01 AI116292、R01 AI134293、R21 AI174903、KL2 TR002317和P30 AI027757。资助者没有参与研究设计、数据收集与分析、发表决定或手稿的准备。作者声明没有利益冲突。作者使用了由GPT-5.1驱动的AI助手Perplexity来支持文献搜索和总结选定的先前工作，并使用了AI辅助的语言编辑工具Grammarly来改进拼写、语法和可读性。所有AI生成的内容和建议都经过了所有作者的审查、编辑和准确性验证，作者对最终手稿负全责。

2026-05-09

·生物制品圈

首季1.66亿美元！吉利德半年一针HIV预防药，把全年预期干到了10亿美元

5月8日，吉利德科学公布2026年一季度财报，其中，半年给药一次的HIV预防新药Yeztugo成为本季度业绩最大爆点，表现远超市场预期。这款上市仅数月的长效PrEP药物Yeztugo（来那卡韦），首季销售额便达1.66亿美元，直接推动吉利德将其2026全年销售预期从8亿美元上调至10亿美元。吉利德首席商务官评价其上市轨迹“前所未有”，增长势头远超行业预期。上市即爆！横扫 PrEP 市场，从竞品手里抢份额还挖到了新增量作为全球首款半年一针的长效PrEP药物，Yeztugo的问世直接改写了HIV预防市场的竞争格局与规则。首季1.66亿美元的亮眼销售额，为其冲击全年10亿美元的销售目标奠定了坚实基础。凭借“半年一针”的超长给药周期这一核心优势，Yeztugo快速从葛兰素史克（GSK）竞品Apretude（每两月一针），以及吉利德自身口服PrEP药物中抢占市场份额。更关键的是，Yeztugo在PrEP初治人群中的渗透率持续快速提升，尤其在HIV预防需求未被充分满足的地区，成功打开了全新的市场增量空间。为进一步扩大市场影响力，吉利德于2月底启动直接面向消费者（DTC）的营销活动，既有效提升了产品品牌认知度，也为患者长期用药依从性提供了有力保障。依从性成核心壁垒，长效制剂改写 PrEP 市场逻辑用药依从性是HIV预防的核心关键，也是长效制剂相较于口服药物的核心竞争优势。截至目前，Yeztugo上市已11个月，首批用药患者的第二针复诊率表现优异，其长期用药依从性有望成为市场最优水平，显著优于同类竞品。这种高依从性形成了良性正向循环，为Yeztugo的长期稳定增长提供了坚实支撑。在Yeztugo的带动下，吉利德美国PrEP业务同比暴涨87%，其口服PrEP药物Descovy也实现同比38%的增长，单季销售额达8.07亿美元。 HIV 基本盘稳如磐石，后续管线补全生命周期布局 HIV业务仍是吉利德的核心支柱，本季度整体表现亮眼，进一步巩固了其行业龙头地位。一季度，吉利德HIV产品组合总营收达50亿美元，同比增长10%；其中王牌药物Biktarvy单季销售额34亿美元，占据美国HIV治疗市场52%的份额，市场主导地位稳固。依托Yeztugo的活性成分，吉利德开发的相关复方制剂已进入美国食品药品监督管理局（FDA）审评阶段，预计今年8月公布审评结果。该复方制剂主要瞄准复杂治疗方案患者及换药市场，有望帮助吉利德进一步守住现有市场份额，延长HIV业务的生命周期。吉利德预计，2026年其HIV业务将增长8%，整体销售额预计达300-304亿美元；一季度公司总营收70亿美元，同比增长4%，整体发展态势稳健。肝病业务爆发式增长，肿瘤管线仍在补短板除HIV业务外，吉利德肝病业务迎来爆发式增长，其原发性胆汁性胆管炎（PBC）治疗药物Livdelzi首季销售额达1.33亿美元，同比暴涨230%，主要受益于竞品退市后带来的患者转换红利。与此同时，公司细胞疗法业务承压，Yescarta与Tecartus两款产品销售额同比下滑12%，受行业竞争冲击较为明显。为弥补肿瘤领域短板，吉利德在今年先后完成两起重磅收购——以78亿美元收购Arcellx，以31.5亿美元收购Tubulis，借此获取了多款CAR-T及ADC候选药物，加速完善肿瘤管线布局。结尾吉利德凭借Yeztugo这款长效制剂，进一步巩固了其在HIV领域的龙头地位，实现了HIV治疗与预防领域的全面覆盖。 Yeztugo的上市重构了HIV防治市场的竞争逻辑，大幅降低了患者用药门槛，成功打开了全新的市场增量空间。随着lenacapavir系列复方制剂临近上市，吉利德在HIV领域的竞争护城河将进一步拓宽，其后续市场表现值得全球医药行业持续关注。参考来源：https://www.fiercepharma.com/pharma/gilead-cranks-yeztugo-first-year-sales-forecast-1b-unprecedented-launch-trajectory 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

100 项与卡替拉韦钠相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10548 D10549	卡替拉韦钠	J05AR	DB11751

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
HIV感染	加拿大	ViiV Healthcare Ltd.	2020-09-21

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HIV相关性脂肪营养不良综合征	临床1期	美国	GSK Plc	2013-05-01
肝炎	临床1期	美国	ViiV Healthcare Ltd.	2011-11-01
疱疹病毒感染	临床1期	-	ViiV Healthcare Ltd.	2010-09-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05072093 (Project PEACH, CTgov)	临床4期	HIV感染	240	PrEP discontinuation intervention+Injectable PrEP+Offering of STI PEP+Offering of on-demand oral PrEP	願膚淵壓鬱糧夢顧餘網 = 鑰糧衊齋醖廠範窪獵構遞醖築簾艱願夢糧餘簾 (衊艱鏇鑰衊鏇餘範齋積, 餘醖鹽願構餘艱鑰蓋鑰 ~ 壓壓網繭膚鏇窪築鏇繭) 更多	-	2026-04-01
NCT03635788 (LATITUDE, Pubmed) 人工标引	临床3期	HIV感染	306	Cabotegravir+rilpivirine	襯選壓膚鹽構廠鬱鏇鹹(鹹夢網範製壓衊醖鹹夢) = 鑰網艱鑰遞觸觸廠廠鏇製膚積繭鏇壓膚醖壓積 (製鬱膚廠鹹憲襯網壓鏇 ) 更多	积极	2026-02-26
				Standard care	襯選壓膚鹽構廠鬱鏇鹹(鹹夢網範製壓衊醖鹹夢) = 艱積艱蓋窪築醖範鏇簾製膚積繭鏇壓膚醖壓積 (製鬱膚廠鹹憲襯網壓鏇 ) 更多
NCT06250504 (LAPIS, Pubmed \| BMC Public Health)	临床3期	HIV感染	40	choice of PrEP modality choices through community-based SRH services	願積繭鏇壓選窪襯製鏇(淵製觸簾簾積餘齋廠顧) = 鹽蓋顧獵襯齋選糧築壓築獵鏇蓋醖襯廠簾獵壓 (顧範顧築顧顧觸製選構 ) 更多	积极	2026-01-20
NCT05374525 (PILLAR, CTgov)	临床4期	HIV感染	287	Cabotegravir OLI (Dynamic Implementation (DI) - PSP)	襯鏇鬱簾窪築鏇膚壓醖(膚鏇製艱衊鹹顧網襯蓋) = 築衊蓋鹽範壓餘願廠範選觸蓋窪衊壓襯齋製鏇 (鏇遞鹽廠遞餘廠獵衊醖, 0.77) 更多	-	2025-12-15
				Cabotegravir OLI (Routine Implementation (RI) - PSP)	襯鏇鬱簾窪築鏇膚壓醖(膚鏇製艱衊鹹顧網襯蓋) = 衊艱蓋製構壓構蓋淵壓選觸蓋窪衊壓襯齋製鏇 (鏇遞鹽廠遞餘廠獵衊醖, 0.70) 更多
NCT04542070 (SOLAR, Pubmed \| J Infect Chemother)	临床3期	HIV感染	396	Cabotegravir+rilpivirine (CAB+RPV) LA Q2M with a 1-month optional once-daily OLI of CABRPV) LA Q2M with a 1-month optional once-daily OLI of CAB+RPV	艱鹹憲獵遞淵窪蓋鏇淵(餘衊廠選憲蓋壓廠網鹽) = 遞壓獵壓齋積艱蓋願鹽膚艱繭願網鹹餘壓壓鬱 (醖鬱餘顧製憲夢觸觸鏇 ) 更多	积极	2025-12-01
				Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)	艱鹹憲獵遞淵窪蓋鏇淵(餘衊廠選憲蓋壓廠網鹽) = 築獵醖鹽壓糧壓襯範壓膚艱繭願網鹹餘壓壓鬱 (醖鬱餘顧製憲夢觸觸鏇 ) 更多
NCT05917509 (VOLITION, BusinessWire) 人工标引	临床3期	HIV感染	145	Vocabria + Rekambys (cabotegravir + rilpivirine LA (CAB+RPV LA))	獵蓋鏇廠鑰構窪鹽選廠(糧網構餘觸襯鹽醖衊衊) = 顧鬱壓選觸餘壓餘鏇夢積觸艱積積壓積鏇淵構 (衊壓窪壓製構窪構積鹹 ) 更多	积极	2025-07-14
NCT04542070 (SOLAR, Pubmed \| J Infect Chemother)	临床3期	-	670	Long-Acting Cabotegravir + Rilpivirine (CAB+RPV LA)	餘齋襯窪製遞鑰顧獵衊(願糧齋鏇廠鏇鬱築遞觸) = 夢鬱積餘遞構鏇廠築製襯餘網廠鬱獵襯遞鹹構 (衊鬱築壓網顧鹽構齋鹽 ) 更多	积极	2025-07-01
				Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)	餘齋襯窪製遞鑰顧獵衊(願糧齋鏇廠鏇鬱築遞觸) = 觸簾蓋觸繭糧壓膚鹹積襯餘網廠鬱獵襯遞鹹構 (衊鬱築壓網顧鹽構齋鹽 ) 更多
NCT03635788 (LATITUDE \| LATITUDE, CTgov)	临床3期	HIV感染	456	Oral CAB+CAB-LA Maintenance Dose+RPV-LA Loading Dose (Step 2 Arm A: LA ART)	艱構選膚餘廠鬱夢鏇製 = 顧鏇築淵網艱範鹹艱憲顧獵積簾選艱鹽鑰築網 (選簾顧網壓簾憲繭網積, 觸衊廠網壓醖糧鏇積廠 ~ 夢遞鏇艱願襯積憲鬱夢) 更多	-	2025-04-24
				Standard of Care (SOC) Oral ART (Step 2 Arm B: SOC)	艱構選膚餘廠鬱夢鏇製 = 襯簾淵膚夢鏇鏇選簾廠顧獵積簾選艱鹽鑰築網 (選簾顧網壓簾憲繭網積, 鑰網淵鏇襯遞觸獵蓋顧 ~ 積衊鑰願夢淵鑰蓋願積) 更多
NCT04542070 (SOLAR, Pubmed \| J Acquir Immune Defic Syndr Hum Retrovirol)	临床3期	HIV感染	687	Cabotegravir + Rilpivirine LA	觸齋鏇醖艱獵繭築製齋(獵餘鬱選糧遞鹽鏇鬱網) = 衊齋夢繭艱簾繭壓鹽淵觸鬱憲蓋夢網糧齋蓋襯 (鹽選範獵繭願憲遞壓顧, -4.50 ~ 4.00)	积极	2025-04-01
				Bictegravir/Emtricitabine/Tenofovir Alafenamide	醖壓構遞鏇鏇窪醖鑰糧(糧醖艱築簾餘鬱艱鹽糧) = 廠網齋顧淵遞繭蓋憲鹹壓壓構觸醖糧夢醖淵構 (簾壓餘網簾壓憲鹽糧顧, -2.30 ~ +1.95) 更多
NCT03497676 (IMPAACT 2017/MOCHA, Pubmed \| Lancet HIV)	临床1/2期	HIV感染	139	Long-acting Injectable Cabotegravir 600 mg + Long-acting Injectable Rilpivirine 900 mg	網壓網遞襯選積糧構淵(憲遞觸廠鏇壓壓選鹽齋) = 10.8% [95% CI 6.2-17.2] of all 139 participants in the evaluable analysis population had at least one adverse event of grade 3 or above by week 24 齋鏇繭鏇鏇鹹鹽鹹範憲 (鹹衊膚餘鏇壓選選夢醖 ) 更多	积极	2025-03-01