Journal of Antimicrobial Chemotherapy最新文献

{"title":"Estimating the herd effects of antimicrobial prevention interventions on ventilator-associated pneumonia within ICU populations: a cluster randomized trial emulation using data from Cochrane reviews.","authors":"James C Hurley","doi":"10.1093/jac/dkaf033","DOIUrl":"10.1093/jac/dkaf033","url":null,"abstract":"<p><strong>Background: </strong>The herd effects of antimicrobial interventions used to prevent ICU-acquired infections are unknown. The objective here was to estimate these herd effects within a single three-tiered cluster randomized trial (CRT) emulated using ventilator-associated pneumonia (VAP) data from randomized concurrent control trials (RCCTs) abstracted within Cochrane reviews.</p><p><strong>Methods: </strong>Control and intervention group data derived from 13 Cochrane reviews of 72 RCCTs of antibiotic (Tier 3) and antiseptic (Tier 2) decontamination versus 109 RCCTs of various non-decontamination (Tier 1, serving as benchmark) VAP prevention interventions were arranged as a three-tiered CRT. The direct and indirect (herd) effects of Tiers 2 and 3 each versus Tier 1 interventions were obtained using estimators derived in meta-regression models.</p><p><strong>Results: </strong>Benchmark (Tier 1) VAP incidences derived for control and intervention groups from non-decontamination RCCTs were 23.3 (95% CI: 20.6-26.1; n = 111) and 19.2 (95% CI: 16.8-21.8; n = 112), respectively. The mean VAP incidences for antibiotic and antiseptic decontamination control groups were 5% to 15% higher than the control group benchmark. The direct effects of antibiotic and antiseptic interventions versus Tier 1 benchmarks (ORs) were 0.77 (95% CI: 0.55-1.09) and 0.97 (95% CI: 0.71-1.33) whereas the indirect effects were 2.17 (95% CI: 1.56-3.03) and 1.38 (95% CI: 1.0-1.91), respectively.</p><p><strong>Conclusions: </strong>Indirect (herd) effects from antimicrobial interventions, although inapparent within individual RCCTs, are strong. These effects on control group VAP incidences, which spuriously conflate the appearance of benefit, constitute herd peril.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1047-1058"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"General practice antibiotic prescriptions attributable to respiratory syncytial virus by age and antibiotic class: an ecological analysis of the English population.","authors":"Lucy Miller, Thomas Beaney, Russell Hope, Mark Cunningham, Julie V Robotham, Koen B Pouwels, Cèire E Costelloe","doi":"10.1093/jac/dkaf043","DOIUrl":"10.1093/jac/dkaf043","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) may contribute to a substantial volume of antibiotic prescriptions in primary care. However, data on the type of antibiotics prescribed for such infections are only available for children <5 years in the UK. Understanding the contribution of RSV to antibiotic prescribing would facilitate predicting the impact of RSV preventative measures on antibiotic use and resistance. The objective of this study was to estimate the proportion of antibiotic prescriptions in English general practice attributable to RSV by age and antibiotic class.</p><p><strong>Methods: </strong>Generalized additive models examined associations between weekly counts of general practice antibiotic prescriptions and laboratory-confirmed respiratory infections from 2015 to 2018, adjusting for temperature, practice holidays and remaining seasonal confounders. We used general practice records from the Clinical Practice Research Datalink and microbiology tests for RSV, influenza, rhinovirus, adenovirus, parainfluenza, human metapneumovirus, Mycoplasma pneumoniae and Streptococcus pneumoniae from England's Second Generation Surveillance System.</p><p><strong>Results: </strong>An estimated 2.1% of antibiotics were attributable to RSV, equating to an average of 640 000 prescriptions annually. Of these, adults ≥75 years contributed to the greatest volume, with an annual average of 149 078 (95% credible interval: 93 733-206 045). Infants 6-23 months had the highest average annual rate at 6580 prescriptions per 100 000 individuals (95% credible interval: 4522-8651). Most RSV-attributable antibiotic prescriptions were penicillins, macrolides or tetracyclines. Adults ≥65 years had a wider range of antibiotic classes associated with RSV compared with younger age groups.</p><p><strong>Conclusions: </strong>Interventions to reduce the burden of RSV, particularly in older adults, could complement current strategies to reduce antibiotic use in England.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1116-1126"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and safety of rifapentine in children: dosing for latent tuberculosis infection.","authors":"Weijian Liu, Nuo Xu, Wei Li, Wen Yao Mak, Tian He, Hongjuan Qin, Shuihua Lu, Hongzhou Lu, Xiaoqiang Xiang, Xiao Zhu, Peize Zhang","doi":"10.1093/jac/dkaf029","DOIUrl":"10.1093/jac/dkaf029","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the safety of 4-week daily rifapentine-isoniazid regimen in latent tuberculosis for Chinese children, and to provide paediatric-specific evidence for extrapolating adult dosing strategies to children.</p><p><strong>Methods: </strong>An open-label, prospective, single-arm clinical trial was conducted among eligible patients (aged <10 years old). Rifapentine concentrations and laboratory safety biomarker (total bilirubin) were analysed and used for population pharmacokinetic-toxicity model development. Simulations were performed to compare efficacy and safety of weight-based and flat-dosing strategy.</p><p><strong>Results: </strong>Once-daily rifapentine treatment was well tolerated: 310 samples (rifapentine n = 139; total bilirubin n = 171) from 36 children (age range 0.89-10 years) were captured well by a joint one-compartment pharmacokinetic with time-varying clearance and an indirect response model. The model adequately described rifapentine autoinduction, reaching a plateau after 21 days and increasing clearance by 70.4%. Simulation suggested that weight-based dosing may cause underexposure in children under 14.5 kg. A flat-dosing strategy could ensure plasma levels within the therapeutic windows. Rifapentine's impact on total bilirubin was within a 2-fold range, and the effect subsided within 5 days after discontinuation.</p><p><strong>Conclusions: </strong>Our study suggested that a flat-dosing strategy of rifapentine was potentially safe and effective for latent tuberculosis infection treatment in Chinese children aged 1 to 10 years old.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1022-1030"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of empiric antibiotics against Pseudomonas aeruginosa on mortality in hospitalized patients: a systematic review and meta-analysis-authors' response.","authors":"Cameron J Hunter, Elizabeth A Marhoffer, Jürgen L Holleck, Samer Ein Alshaeba, Alyssa A Grimshaw, Andrew Chou, George B Carey, Craig G Gunderson","doi":"10.1093/jac/dkaf047","DOIUrl":"10.1093/jac/dkaf047","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1162"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of the REverSe TRanscrIptase Chain Termination assay for measuring tenofovir diphosphate in dried blood spots from a clinical pharmacokinetic trial.","authors":"Benjamin P Sullivan, Cosette A Craig, Andrew T Bender, Emily Blake, Oraphan Siriprakaisil, Pra-Ornsuda Sukrakanchana, Tim R Cressey, Paul K Drain, Ayokunle O Olanrewaju, Jonathan D Posner","doi":"10.1093/jac/dkaf049","DOIUrl":"10.1093/jac/dkaf049","url":null,"abstract":"<p><strong>Background: </strong>Tenofovir diphosphate concentration in red blood cells is an objective measure of long-term oral pre-exposure prophylaxis (PrEP) or antiretroviral therapy (ART) adherence. However, current methods for measuring tenofovir diphosphate are equipment and capital intensive, limiting widespread adoption.</p><p><strong>Objectives: </strong>Low cost, rapid diagnostics for measuring tenofovir diphosphate may drive clinical adoption of routine drug level measurement as a tool for adherence monitoring of tenofovir disoproxil fumarate-based PrEP or ART. We validate a simple and accessible enzymatic assay [REverSe TRanscrIptase Chain Termination (RESTRICT)] for measuring tenofovir diphosphate in dried blood spots (DBS) obtained from a directly observed therapy study of individuals on PrEP.</p><p><strong>Methods: </strong>We performed RESTRICT measurements on 74 DBS samples from individuals on tenofovir disoproxil fumarate/emtricitabine regimens. We compared RESTRICT measurements with those from a gold-standard method of liquid chromatography tandem mass spectrometry (LC-MS/MS). The ability of RESTRICT to correctly classify DBS tenofovir diphosphate concentrations to established steady-state adherence benchmark concentrations was determined using area under receiver operating characteristic curves (AUCs).</p><p><strong>Results: </strong>The RESTRICT measurements of DBS samples were highly correlated with LC-MS/MS measurements of tenofovir diphosphate from DBS (r = -0.90; P < 0.0001). The RESTRICT assay correctly classified DBS samples as above or below established steady-state adherence benchmark concentrations corresponding to low (AUC = 0.974), moderate (AUC = 0.936) and high (AUC = 0.955) levels of adherence.</p><p><strong>Conclusions: </strong>The enzymatic RESTRICT assay can accurately measure tenofovir diphosphate concentrations in DBS specimens using simple procedures and readily available laboratory equipment, offering accessible objective adherence monitoring for persons receiving tenofovir disoproxil fumarate-based PrEP or ART.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1141-1147"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing phenotypic effect of integrase strand-transfer inhibitor (INSTI)-based resistance substitutions associated with failures on cabotegravir.","authors":"Michelle L D'Antoni, Brie Falkard, Kristen Andreatta, Stephanie Cox, Cal Cohen, Christian Callebaut","doi":"10.1093/jac/dkaf019","DOIUrl":"10.1093/jac/dkaf019","url":null,"abstract":"<p><strong>Objectives: </strong>International guidelines recommend integrase strand-transfer inhibitor (INSTI)-based regimens as initial and switch therapy in people with HIV. As novel INSTIs become available, understanding how emergence of resistance at virological failures and seroconversions affects subsequent treatment options is needed. For the latest approved INSTI, cabotegravir, resistance patterns comprising Q148K/R, N155H, R263K, G118R, E138A/K and G140A/S (alone or in combination) have been documented in virological failures and seroconversions. Here, the effect of these substitutions on antiviral activity of commercially approved INSTIs, bictegravir and elvitegravir, was assessed.</p><p><strong>Methods: </strong>Antiviral testing was performed using person-derived clinical isolates (n = 52) with viral profiles similar to cabotegravir INSTI resistance patterns; susceptibility to cabotegravir, bictegravir and elvitegravir was measured using a phenotypic assay. Substitution patterns from isolates included triple [Q148K/H/R + E138A/K + G140A/C/S (n = 16)], double [Q148R + E138K (n = 3); Q148H/R + G140A/S (n = 24)] and single [N155H (n = 6); Q148R (n = 3)] resistance-associated mutations (RAMs).</p><p><strong>Results: </strong>IC50 fold changes (FCs) for triple RAMs were the highest, at 47.0, 7.59 and >144 for cabotegravir, bictegravir and elvitegravir, respectively. For cabotegravir, bictegravir and elvitegravir, respectively, mean IC50 FCs were 9.5, 2.5 and >144 for double RAMs; and 3.3, 1.4 and >65 for single RAMs. When considering clinical/biological assay cut-offs, 54% (28/52) of isolates were susceptible to bictegravir, 40% (21/52) were partially susceptible and 6% (3/52) were resistant; for elvitegravir, 100% of isolates were resistant. Cabotegravir cut-offs were not available at the time of reporting.</p><p><strong>Conclusions: </strong>Overall, clinical isolates with RAM patterns similar to clinically observed cabotegravir INSTI resistance showed meaningful increases in IC50 FCs, suggesting that cabotegravir-associated resistance may negatively affect efficacy of bictegravir- and elvitegravir-based regimens.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"962-966"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential risk of cross-resistance to voriconazole in HIV/AIDS patients with Talaromyces marneffei infection and the mechanisms of the cross-resistance.","authors":"Yan-Qing Zheng, Qiang-Guo Li, Jean-Paul Latge, Xi-Ke Tang, Al-Odaini Najwa, Kai-Su Pan, Shi-Xiong Yang, Cun-Wei Cao","doi":"10.1093/jac/dkaf022","DOIUrl":"10.1093/jac/dkaf022","url":null,"abstract":"<p><strong>Background: </strong>The use of fluconazole for long-term oral candidiasis treatment in HIV/AIDS patients can potentially affect the clearance rate and antifungal efficacy of voriconazole against Talaromyces marneffei infection. We isolated two T. marneffei strains that were both resistant to fluconazole and voriconazole. To investigate the mechanism underlying the induction of the cross-resistance in T. marneffei.</p><p><strong>Methods: </strong>Fluconazole-resistant strains were induced in vitro. The target enzyme 14-α sterol demethylase Cyp51B was sequenced, and drug efflux pump expression was determined by RT-qPCR in all strains.</p><p><strong>Results: </strong>The sensitivity of fluconazole-induced resistant strains to fluconazole was greater than 128 mg/L, and this resistance was stably inherited after fluconazole pressure was removed. MICs of voriconazole for resistant strains were 4∼16 times greater than FRR (0.25-1 versus 0.06 mg/L). Two mutation hotspots in Cyp51B were detected: G441D and G441V. The AtrF, Mdr1 and Pmfcz genes were significantly overexpressed in the vast majority of the fluconazole-resistant strains (P < 0.05).</p><p><strong>Conclusions: </strong>The growth of T. marneffei in the presence of fluconazole could induce voriconazole resistance in vitro. The main cause of this cross-resistance in T. marneffei appears to be related to a mutation in Cyp51B at G441 and overexpression of the efflux pumps AtrF, Mdr1 and Pmfcz.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"976-979"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subtypes A1 and D, and recombinant HIV-1 natural polymorphisms associated with lenacapavir drug resistance in Uganda.","authors":"Daniel Omoding, Nicholas Musinguzi, Yap Boum, Conrad Muzoora, Simone Kigozi, Peter W Hunt, Jeffrey N Martin, David R Bangsberg, Jessica E Haberer, Mark J Siedner, Suzanne M McCluskey, Guinevere Q Lee","doi":"10.1093/jac/dkaf018","DOIUrl":"10.1093/jac/dkaf018","url":null,"abstract":"<p><strong>Background: </strong>Lenacapavir, a novel HIV-1 capsid inhibitor, shows promise for treating MDR HIV-1, as well as for pre-exposure prophylaxis (PrEP) in prevention of HIV infection. Its unique mechanism and lack of cross-resistance with other antiretroviral classes make lenacapavir a significant addition to HIV therapy. The clinical trials CALIBRATE and CAPELLA have demonstrated high viral suppression rates in both ART-naive individuals and individuals with MDR HIV-1. Lenacapavir-associated resistance mutations, such as M66I and Q67H, rarely seen as natural polymorphisms in lenacapavir-naive populations, are predominantly studied in subtype B HIV-1.</p><p><strong>Objectives: </strong>Our study aimed to investigate the prevalence of lenacapavir resistance-associated mutations in HIV-1 subtypes A1 and D in a cohort of individuals living with HIV-1 from southwestern Uganda.</p><p><strong>Methods: </strong>Utilizing plasma samples from ART-naive adults living in Uganda, HIV-1 Gag p24 (capsid) sequences were analysed for lenacapavir resistance mutations.</p><p><strong>Results: </strong>Among 546 lenacapavir-naive participants, no major lenacapavir resistance-associated mutations were found. Minor mutations were present in 1.6% of participants, with T107A being the most common. Longitudinal data indicated the persistence of T107A for at least 3 years post-ART initiation in one participant. Phylogenetic analysis indicated individuals carrying T107A were found independently in distinct locations within the tree, suggesting that T107A might have arisen from multiple distinct base substitution events. Shannon entropy analysis showed high variability in certain capsid sites, but none overlapped with known lenacapavir resistance sites.</p><p><strong>Conclusions: </strong>These findings suggest a low prevalence of naturally occurring lenacapavir resistance mutations in Uganda, supporting lenacapavir's potential efficacy in this region.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"955-961"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world efficacy and tolerability of CAB+RPV LA in women: addressing the gender gap in HIV treatment research.","authors":"Marta Rosas Cancio-Suárez, Ana Moreno, Santos Del Campo Terrón, María Jesús Vivancos, Alejandro G García-Ruiz De Morales, Javier Martínez-Sanz, Raquel Ron, Sofía Sánchez-Izquierdo, Manuel Vélez-Díaz-Pallarés, Santiago Moreno, María Jesús Pérez-Elías","doi":"10.1093/jac/dkaf038","DOIUrl":"10.1093/jac/dkaf038","url":null,"abstract":"<p><strong>Background: </strong>Women, particularly those of advanced age with comorbidities and polypharmacy, are often underrepresented in clinical trials evaluating long-acting (LA) antiretroviral therapy (ART) regimens like cabotegravir and rilpivirine (CAB + RPV LA). This single-center study aims to address this gap by assessing the effectiveness, tolerability, and adherence to CAB + RPV LA, focusing on women who often have complex health profiles.</p><p><strong>Methods: </strong>In this single-center, retrospective study, we analyzed virologic suppression rates, adherence and tolerability in our cohort of women living with HIV comparing their outcomes to men on the same regimen.</p><p><strong>Results: </strong>A total of 270 individuals (42 women and 228 men) were included. Women had a higher prevalence of comorbidities (86% versus 49%, P = 0.0001), and were more likely to have used ≥5 ART lines (69% versus 29%, P < 0.0001), and 31% were aged ≥60 years compared to 13% of men (P = 0.003). Despite higher rates of comorbidities and polypharmacy, women achieved virologic suppression and adherence levels comparable to men. CAB + RPV LA was well-tolerated in both groups, with no significant gender-based differences in treatment outcomes.</p><p><strong>Conclusion: </strong>CAB + RPV LA is effective and well-tolerated in women with complex ART histories, providing a viable long-acting alternative for populations traditionally underrepresented in clinical trials. These findings underscore the importance of including women in studies of novel ART regimens to ensure equitable access and outcomes.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"1084-1088"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of drug resistance mutations in low-level viremia patients under antiretroviral therapy in Southwestern China: a cross-sectional study.","authors":"Yuanlu Shu, Jiafa Liu, Cuixian Yang, Jianjian Li, Mi Zhang, Yuan Li, Xuemei Deng, Xingqi Dong","doi":"10.1093/jac/dkaf017","DOIUrl":"10.1093/jac/dkaf017","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the prevalence and characteristics of drug resistance mutations (DRMs) in patients with low-level viremia (LLV) in Southwestern China, as it has become a growing challenge in AIDS clinical practice.</p><p><strong>Methods: </strong>This cross-sectional study was performed in Yunnan Province, Southwestern China. LLV was defined as 50-999 copies/mL of plasma viral load with antiretroviral therapy (ART) for at least 6 months. HIV-1 DRM detection used validated in-house protocol.</p><p><strong>Results: </strong>A total of 470 sequences were obtained, and 13 HIV-1 genotypes were identified, among which CRF08_BC (47.5%), CRF07_BC (22.3%) and CRF01_AE (10.0%) subtypes were the most prevalent. The overall prevalence of DRMs was 45.7% (215/470), and the prevalence of DRMs to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 39.4% (185/470), 20.6% (97/470) and 5.3% (25/470), respectively. The most common NNRTI-associated mutations were K103N (16.0%), E138A (6.6%), V179D (6.6%) and P225H (4.9%), and those in NRTIs were M184V (17.0%), D67N (3.4%) and K65R (3.0%). PI-associated mutations were infrequent, occurring in less than 1.8% of cases. The prevalence of NNRTI-associated mutations (K101E and Y188C) was found to be statistically significant among various LLV groups. Additionally, significant variations were observed in the prevalence of NNRTI-associated mutations (V106I, V106M, E138A and P225H), NRTI-associated mutation (K65R) and PI-associated mutations (L33F and Q58E) across different subtypes.</p><p><strong>Conclusions: </strong>The prevalence of DRMs in ART-experienced patients with LLV was high, and HIV-1 genotypes exhibited diversity in Yunnan Province. These findings indicate that regular DRM monitoring during LLV episodes was essential for effective clinical treatment and management in this region.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"947-954"},"PeriodicalIF":3.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}