To evaluate the associations of plasma EBV-DNA and tumor EBV status with clinical outcomes in patients with AIDS-related non-Hodgkin lymphoma (ARL). We retrospectively analyzed ARL patients diagnosed at Shanghai Public Health Clinical Center between 2013 and 2021. Tumor EBV status was determined by EBV-encoded RNA (EBER) in situ hybridization, and plasma EBV-DNA was quantified using real-time PCR. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox regression. Longitudinal EBV-DNA patterns during chemotherapy were classified into four groups: persistently negative, persistently positive, clearance, and conversion. Among 183 ARL patients, 99 underwent tumor EBER testing with 45.5
BACKGROUND:Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLWH). While tuberculosis preventive treatment (TPT) is universally recommended for PLWH with latent TB infection (LTBI), its necessity for interferon-gamma release assay (IGRA)-negative individuals initiating antiretroviral therapy (ART) is controversial. Therefore, this study aimed to investigate whether TPT is necessary in this specific population. METHODS:We conducted a retrospective cohort study of ART-naïve PLWH with a negative IGRA without prior anti-tuberculosis drug use or active TB at Shanghai Public Health Clinical Center from 2020 to 2024. Demographic characteristics, laboratory results, and TB occurrence during follow-up were recorded. Kaplan-Meier analysis, Cox proportional hazards models, and restricted cubic splines were used to identify risk factors and model the dose-response relationship between CD4 + T-cell count and TB risk. RESULTS:Among 686 participants (89.4% male, median age 41), the median CD4 + T-cell count was 35.52 cells/µL. During a 26-month median follow-up, 22 patients developed TB (incidence: 13.41/1000 person-years). All TB cases occurred in the 583 patients with CD4 + T-cell count < 200 cells/µL (incidence: 15.61/1000 person-years), while no events occurred in those with CD4 + T-cell count ≥ 200 cells/µL. Lower CD4 + T-cell count and residence in high-risk areas (adjusted Hazard Ratio [aHR] = 3.65, 95% CI: 1.35-9.89) were independent risk factors for active TB. A continuous log-linear inverse relationship between CD4 + T-cell count and TB risk was identified, with progressively higher risk at lower CD4 levels. CONCLUSION:IGRA-negative PLWH with CD4 + T-cell count < 200 cells/µL and high-risk area residence may be considered as priority candidates for TPT. This risk-stratification framework warrants prospective validation.
Cytomegalovirus (CMV) pneumonia presents diagnostic challenges in AIDS patients, as plasma monitoring often fails to reflect pulmonary viral burden. This retrospective study evaluated the prognostic value of bronchoalveolar lavage fluid (BALF) CMV DNA loads in 189 AIDS patients with pulmonary infections and CD4+ T cell counts < 200 cells/μL. CMV DNA in BALF and plasma was quantified to analyze associations with immune status and 90-day all-cause mortality. CMV detection was significantly more frequent in BALF (49.7%) than plasma (26.6%), indicating viral compartmentalization. An optimal BALF cutoff of 10,000 copies/mL was established for mortality prediction. Patients exceeding this threshold exhibited significantly lower CD4+ counts, increased mechanical ventilation requirements (34.4% vs. 11.5%), and prolonged hospital stays. Crucially, a BALF CMV load > 10,000 copies/mL was identified as an independent predictor of 90-day mortality (adjusted odds ratio = 3.78; 95% CI: 1.12–12.71). In conclusion, pulmonary CMV replication is prevalent and often compartmentalized in AIDS patients. A BALF CMV DNA load exceeding 10,000 copies/mL serves as a biomarker of profound immunosuppression and independently predicts poor clinical outcomes, highlighting the necessity of quantitative BALF monitoring for risk stratification.
Aims:This study aims to systematically compare the clinical characteristics of tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases in AIDS patients,and to identify independent predictors for differential diagnosis. Methods:Clinical data of AIDS patients co-infected with TB or NTM at Shanghai Public Health Clinical Center (January 2019 - January 2024) were retrospectively analyzed. Univariate comparisons were performed using t-test, Mann-Whitney U test, χ2 or Fisher's exact test, with Bonferroni correction for multiple comparisons. Multivariate binary logistic regression (Enter method) was used to adjust for age, gender, CD4+ T-cell count, C-reactive protein (CRP), procalcitonin, neutrophil count, miliary nodules, and superficial lymphadenopathy. Results:A total of 494 patients were included (AIDS/TB: 206, AIDS/NTM: 288). The predominant NTM species was Mycobacterium avium (68.2%), followed by Mycobacterium kansasii (13.6%) and Mycobacterium intracellulare (10.9%). After Bonferroni correction, AIDS/NTM patients had significantly higher rates of Pneumocystis jirovecii pneumonia, cytomegalovirus infection, and progressive multifocal leukoencephalopathy (all P < 0.0083). Among clinical symptoms, only enlarged lymph nodes remained significantly more common in the TB group after correction (P = 0.002). Multivariate analysis showed that male gender (adjusted OR for NTM vs. TB = 0.451, 95% CI: 0.208-0.979, P = 0.044), higher CD4+ count (per 10 cells/μL: OR = 0.98, 95% CI: 0.96-0.99, P = 0.005), higher CRP (per 10 mg/L: OR = 0.90, 95% CI: 0.86-0.95, P < 0.001), higher neutrophil count (OR = 0.903 per 1 × 10(Akokuebere et al., 20249)/L, 95% CI: 0.836-0.976, P = 0.010), presence of miliary nodules (OR = 0.079, 95% CI: 0.027-0.233, P < 0.001), and presence of superficial lymphadenopathy (OR = 0.565, 95% CI: 0.327-0.977, P = 0.041) were independently associated with lower odds of NTM disease (i.e., associated with TB). Imaging revealed that only miliary nodules remained significantly more common in TB after Bonferroni correction (P < 0.001). Conclusions:While AIDS/TB and AIDS/NTM share many clinical similarities, the presence of miliary nodules, superficial lymphadenopathy, higher inflammatory markers (CRP, neutrophils), higher CD4+ count, and male gender favor TB. These findings can assist clinicians in differentiating the two infections when rapid microbiological results are unavailable. The high prevalence of Mycobacterium avium (68.2%) suggests that empirical therapy for suspected NTM in severely immunocompromised AIDS patients in Shanghai should cover the Mycobacterium avium complex (MAC). Prospective multicenter studies with pre-specified outcomes are needed to validate our findings.
This study evaluates the potential of plasma extracellular vesicle (EV)-associated miRNAs as diagnostic and differential-diagnostic biomarkers to distinguish tuberculosis (TB) from non-tuberculous mycobacterial infection (NTM) among AIDS patients. A cohort of 125 AIDS patients admitted to the Infectious Diseases and Immunology Department of Shanghai Public Health Clinical Center from January 2021 to January 2024 was categorized into AIDS/TB, AIDS/NTM, and AIDS control groups; in the discovery phase, 15 cases (AIDS/TB: 3, AIDS/NTM: 9, AIDS controls: 3) were used to isolate plasma-derived EVs and perform high-throughput sequencing to construct miRNA expression profiles, followed by validation in a large-sample cohort of 110 cases using qPCR. Diagnostic and differential diagnostic value were evaluated with ROC curves, area under the curve (AUC), and the Youden index. In the discovery phase, differentially expressed EV-associated miRNAs were observed among the three groups and among different NTM species; miR-374a-5p and miR-652-3p were markedly downregulated in AIDS/NTM versus AIDS/TB and AIDS controls, while let-7c-5p was upregulated in both AIDS/NTM and AIDS/TB versus AIDS controls. In the validation phase (n=110), miR-374a-5p showed no significant difference between AIDS/TB and AIDS controls but was lower in AIDS/NTM; miR-652-3p was higher in AIDS/TB than controls and lower in AIDS/NTM than controls and AIDS/TB; let-7c-5p was significantly higher in both AIDS/TB and AIDS/NTM than controls, with AIDS/NTM higher than AIDS/TB. ROC analyses yielded: AIDS control vs AIDS/NTM—miR-374a-5p AUC 0.7263, miR-652-3p AUC 0.9947, let-7c-5p AUC 1.0000; AIDS control vs AIDS/TB—miR-374a-5p AUC 0.6800, miR-652-3p AUC 0.7900, let-7c-5p AUC 1.0000; AIDS/NTM vs AIDS/TB—miR-374a-5p AUC 0.8220, miR-652-3p AUC 0.9993, let-7c-5p AUC 0.6613. Collectively, plasma EV-associated miR-374a-5p, miR-652-3p, and let-7c-5p show potential as diagnostic and differential-diagnostic biomarkers for distinguishing TB from NTM infections in AIDS patients, offering a prospective direction for TB/NTM diagnostic strategies in this population.
Long-term use of tenofovir disoproxil fumarate (TDF) is associated with renal tubular dysfunction and bone mineral loss. In virologically suppressed people living with HIV (PLWH), optimizing antiretroviral therapy requires maintaining viral suppression while minimizing cumulative drug-related toxicity. We therefore evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) in Chinese PLWH with TDF-related renal or bone toxicity. This prospective, single-center, open-label cohort study enrolled adults with HIV-1 RNA < 40 copies/ml for ≥ 6 months on TDF-based regimens and evidence of TDF-associated renal or bone toxicity. Participants were switched to DTG/3TC and followed for 48 weeks. The primary endpoint was virological failure at week 48 (FDA Snapshot algorithm). Secondary endpoints included changes in CD4 + T-cell counts, renal tubular biomarkers, bone mineral density (BMD), metabolic parameters, and safety outcomes. One hundred participants were enrolled; 91 completed the study per protocol. Median age was 45 years and 90
ObjectiveTo characterize gut microbiome alterations and microbial translocation in human immunodeficiency virus (HIV)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected patients and identify microbial signatures associated with COVID-19 severity.MethodsIn this cohort study, blood and fecal samples from 38 HIV/AIDS patients (20 SARS-CoV-2 co-infected [PC group]; 18 SARS-CoV-2-negative [NC group]) were analyzed. The PC group was stratified by COVID-19 severity: mild-to-moderate (PC1, n=13), severe-to-critical (PC2, n=3), and mixed infections (PC3, n=4). Serum lipopolysaccharide (LPS), soluble CD14 (sCD14), and zonulin levels were measured to assess microbial translocation and gut barrier integrity. Fecal metagenomic profiling was performed via whole-genome shotgun sequencing (Illumina NovaSeq/HiSeq).ResultsCo-infected patients exhibited significantly elevated plasma LPS (78.09 vs 48.72 pg/mL, p=0.032) and sCD14 (2667 vs 1927 ng/mL, p=0.0015) compared to controls. Although no differences in α-diversity or overall taxonomic abundance were observed between the PC and NC groups, 329 PC-unique and 216 NC-unique microbial species were identified. Nine genera demonstrated diagnostic potential for co-infection [Area Under the Curve (AUC), >0.7] with Akkermansia showing the highest predictive value (AUC = 0.811). Critically, Blautia abundance was significantly reduced in severe-to-critical cases (PC2) versus mild-moderate cases (PC1, p=0.043) and controls (NC, p=0.006). Besides, our function prediction for gut microbiota suggested that SARS-CoV-2 may exacerbate lipid metabolic dysregulation in HIV-infected individuals.ConclusionsHIV/SARS-CoV-2 co-infection is characterized by heightened microbial translocation and species-specific microbiota alterations rather than global dysbiosis. Blautia depletion may correlate with COVID-19 severity.
BACKGROUND:Dolutegravir (DTG), a cornerstone of human immunodeficiency virus-1 (HIV-1) treatment, is primarily metabolized by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in the UGT1A1 gene have been shown to influence the pharmacokinetics of DTG across different ethnic populations. This study aims to characterize the distribution of UGT1A1 polymorphic alleles and evaluate their impact on DTG plasma trough concentrations in Han Chinese individuals living with HIV-1 infection. METHODS:This study enrolled Han Chinese adults from the Outpatient Department of Infection and Immunity, Shanghai Public Health Clinical Center, between September 2 and November 2, 2024, who were infected with HIV-1 and had been receiving DTG treatment for at least 10 days. Seven segments of the UGT1A1 gene, including exons 1-5, the promoter TATA box, and the phenobarbital-responsive enhancer module (PBREM), were amplified to identify potential polymorphisms. The association between these gene polymorphisms and DTG plasma trough concentrations was investigated. RESULTS:A total of 287 Han Chinese with HIV-1 infection were included in the study, of which 96.2% (276/287) were male, with a median age of 40 years (interquartile range [IQR]: 32-51 years). The median trough concentration of DTG was 2427 ng/mL (IQR: 1807-3107 ng/mL). The three most common alleles identified were (1) 211G>A in exon 1 (UGT1A1*6, rs4148323), (2) seven TA repeats in TATA box (UGT1A1*28, rs3064744), and (3) -3279T>G in PBREM (UGT1A1*60, rs4124874). The percentages of heterozygotes for these alleles were 31.7%, 22.0%, and 49.1%, respectively, while the frequencies of homozygotes were 4.2%, 1.4%, and 8.0%, respectively. Plasma trough concentrations of DTG were significantly higher in patients carrying one or two alleles of UGT1A1*6 compared to those with the wild-type genotype (P <0.001). However, neither UGT1A1*28 nor UGT1A1*60 alone significantly affected DTG trough concentrations. Multiple linear regression analysis revealed that low body weight, the presence of one or two UGT1A1*6 alleles, and compound heterozygote of UGT1A1*6/*60 or UGT1A1*6/*28/*60 were independent risk factors associated with high DTG plasma trough concentrations. CONCLUSIONS:The frequencies of heterozygotes for UGT1A1*6, UGT1A1*28, and UGT1A1*60 were found to be high in the studied population. In addition to low body weight, the presence of UGT1A1*6 and compound heterozygosity of UGT1A1*6/*60 or UGT1A1*6/*28/*60 were significant factors contributing to elevated DTG trough concentrations.
Background People living with HIV (PWH) are at increased risk of cardiovascular disease; however, evidence from Asian populations remains limited. We evaluated the prevalence and characteristics of carotid plaques among PWH and people without HIV (PWoH) in China to examine the impact of HIV infection on subclinical atherosclerosis.Methods In this cross-sectional study conducted at the Shanghai Public Health Clinical Center, China, we enrolled 1390 PWH and 1390 age-frequency and sex-frequency matched PWoH aged 40 years or older. Carotid ultrasonography was used to assess the presence, number and echogenicity of carotid plaques.Results The prevalence of carotid plaques was significantly higher in PWH than in PWoH (45.3% vs 37.5%, p<0.001), and the prevalence of echo-lucent plaques was also higher (21.1% vs 18.0%, p=0.045). Among participants with carotid plaques, PWH were more likely to have three or more plaques (35.8% vs 21.2%, p<0.001) and a greater maximum plaque thickness (2.0 mm vs 1.9 mm; p=0.026). After adjustment for age, sex and dyslipidaemia, HIV infection remained independently associated with increased odds of carotid plaques (adjusted OR (aOR)=1.45; 95% CI 1.23 to 1.70) and echo-lucent plaques (aOR=1.24; 95% CI 1.02 to 1.50). Associations were strongest among men and younger participants. No HIV-related clinical factors were significantly associated with carotid plaque presence.Conclusion HIV infection is independently associated with an increased carotid plaque burden and echo-lucent plaque features, suggesting accelerated atherosclerosis beyond traditional risk factors. These findings support routine cardiovascular risk assessment and early preventive strategies in PWH.
The underlying mechanisms and diagnostic biomarkers for the progress of COVID-19 in HIV patients have not been fully elucidated. In this study, the aim is to analyze the metabolomic profiles of HIV/AIDS patients co-infected with SARS-CoV-2 and to identify biomarkers indicative of co-infection. In this study, we conducted a retrospective cohort analysis of peripheral blood samples collected from 30 HIV/AIDS patients co-infected with SARS-CoV-2 (pc group) and 30 patients without SARS-CoV-2 (nc group). In this study, through non-targeted metabolomics and lipidomics analysis, 77 differential metabolites were identified in the plasma of patients co-infected with HIV and SARS-CoV-2 compared to the nc group, with vitamin K1 emerging as a significant feature. Moreover, the plasma of the pc group showed disturbances in lipid metabolism, with elevated triglycerides (TG) and phosphatidylcholine (PC) and decreased phosphatidylglycerol (PG) compared to the control group. Vitamin K1 may be a biomarker for SARS-CoV-2 in HIV/AIDS patients, and changes in the levels of TG, PC, and PG molecules appear to be the main features following HIV co-infection with COVID-19. The emphasis in our study is on the power of using comprehensive metabolomics (lipidomics) approaches to identify metabolic biomarkers and potential mechanisms of COVID-19 in HIV/AIDS patients.
BackgroundIntracranial imaging abnormalities are commonly observed in patients suffering from HIV-associated cryptococcal meningitis, both before and during the treatment period. This study aims to analyze the prevalence, origins, radiological characteristics, treatments, and prognosis of intracranial lesions in patients with HIV-associated cryptococcal meningitis, thereby providing references for future clinical decision-making.MethodsThe clinical data of patients diagnosed with HIV-associated cryptococcal meningitis and admitted to the Shanghai Public Health Clinical Centre between 2013 and 2019 were collected. Logistic regression analysis was subsequently conducted to identify potential risk factors associated with the development of intracranial lesions in this patient group.ResultsOf 211 patients analyzed, 64.5% (136/211) had intracranial lesions during treatment and follow-up. Initial cranial imaging showed 60% had lesions pre-treatment. Throughout treatment, 32.7% (52/159) developed new or worsened lesions. Mortality rates at 2 weeks, 8 weeks, and 2 years for those with detected lesions were 3%, 7.6%, and 13.2%, respectively. Lesions were primarily caused by Cryptococcus (70.5%) and Mycobacterium (24.3%). Lacunar infarcts, especially in the basal ganglia, were the most common type. Patients aged 50 years or older, and those presenting with altered mental status upon admission, were found to be more likely to have intracranial lesions at baseline, with adjusted odds ratios of 5.364 (95% CI: 1.468-19.591, P=0.011) and 7.970 (95% CI: 2.241-28.337, P=0.001), respectively. Patients with lesion progression showed higher levels of IFN-γ, IL-4, IL-5, IL-6, IL-1Ra, IL-1β, GM-CSF, Eotaxin, and Basic FGF in cerebrospinal fluid after four weeks of treatment.ConclusionIntracranial lesions in HIV-associated cryptococcal meningitis patients are mostly due to Cryptococcus and Mycobacterium infections. They often appear as lacunar infarcts, predominantly in the basal ganglia, and can worsen with treatment initiation, possibly due to higher baseline cytokine levels in cerebrospinal fluid.
Tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy regimens remain one of the first-line treatments in many countries. We assessed the changes of bone mineral density (BMD) in people with HIV (PWH) who had early switch from TDF-based regimens to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). This 48-week, multicenter, randomized, open-label clinical trial recruited adult PWH on TDF-based regimens with virological suppression for at least 24 weeks. Participants were randomly assigned (1:1) to immediately switch to B/F/TAF (immediate switch group) or switch after 24 weeks (deferred switch group). The primary endpoint was the median percentage change [interquartile range (IQR)] in BMD from baseline to week 48. Between December 17, 2021 and February 21, 2023, 150 PWH were randomly assigned to immediate switch group (n = 75) or deferred switch group (n = 75). At week 48, no significant difference in BMD changes of the spine was observed at week 48 [3.30
Sepsis is a leading cause of death among patients with HIV, but early diagnosis remains a challenge. This study evaluates the diagnostic performance of monocyte distribution width (MDW) in detecting sepsis in patients with HIV. A prospective observational study was conducted at Shanghai Public Health Center, involving 488 hospitalized patients with HIV aged 18-65 between December 2022 and August 2023. MDW was measured at admission, and its diagnostic accuracy was compared with Sepsis-3 criteria. Survival rates on day 28 and 90 were also recorded. Additionally, five machine learning (ML) models were tested to enhance diagnostic efficacy. Of 488 subjects, 90 were in the sepsis group and 398 in the control group. MDW showed a diagnostic area under the curve (AUC) of 0.82, comparable to C-reactive protein (CRP) and Procalcitonin (PCT) with AUCs of 0.78 and 0.82, respectively. With a cut-off value of 25.25, MDW had a sensitivity of 0.83 and specificity of 0.76. The positive and negative predictive values were 44% and 95%, respectively. When MDW was combined with platelet count, serum albumin, and hemoglobin in a random forest model, the AUC improved to 0.931. The model achieved a sensitivity of 1.00 and specificity of 0.732. MDW is a useful diagnostic marker for sepsis in patients with HIV, with strong sensitivity and specificity. Combining MDW with other lab markers can further enhance diagnostic accuracy.Trial registration: ClinicalTrials.gov identifier: NCT05036928..
Introduction. Lamivudine plus dolutegravir (3TC/DTG) and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimens are commonly used as first-line treatments for people living with human immunodeficiency virus (HIV) (PLWH) worldwide. Gap Statement. There are limited comparative data on the antiviral activity and safety between these regimens in ART-naive PLWH, particularly in China, where the 3TC/DTG regimen was integrated into first-line therapy in 2021 and gained broader adoption after its inclusion in the National Health Insurance in 2022. Aims. This study aims to provide real-world evidence comparing the 3TC/DTG regimen to the B/F/TAF regimen in ART-naive PLWH in China. Methodology. This retrospective study enrolled PLWH initiating ART with either 3TC/DTG or B/F/TAF in Shanghai from January 2020 to January 2023. Demographic characteristics and clinical information were collected and compared for each patient. Results. A total of 380 eligible, ART-naive PLWH were included, with 190 patients in the 3TC/DTG group and 190 patients in the B/F/TAF group. Following the initiation of ART, most patients (94.1 and 89.3% for 3TC/DTG and B/F/TAF groups, respectively) achieved viral suppression (<50 copies of HIV RNA per millilitre) at week 24. The CD4 cell count significantly increased from a baseline of 301.3±185.8 cells per microlitre to 479.5±229.3 cells per microlitre at week 36 for the 3TC/DTG group and from 289.2±188.8 cells per microlitre at baseline to 487.8±234.2 cells per microlitre at week 36 for the B/F/TAF group. Both groups experienced an increase in blood lipid levels after initiating ART, with higher levels of high-density lipoprotein cholesterol (HDL-C) observed in the 3TC/DTG group compared with the B/F/TAF group. Renal and hepatic function indicators remained stable in both groups. Conclusions. 3TC/DTG demonstrates similar antiviral efficacy to B/F/TAF and does not significantly impact liver and kidney functions. Patients receiving 3TC/DTG showed higher plasma HDL-C levels compared with those on B/F/TAF, which confer long-term clinical benefits in reducing cardiovascular risk.
BackgroundThe interaction between human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections presents a critical challenge to immunopathogenesis. While HIV infection induces progressive CD4+ T cell depletion and chronic immune dysfunction, SARS-CoV-2 triggers complex host responses, ranging from localized antiviral defense to systemic hyperinflammation. We aimed to illustrate the plasma proteomic profiles of hospitalized patients coinfected with HIV and SARS-CoV-2.MethodsLiquid chromatography-tandem mass spectrometry was used to analyze the plasma protein profiles in three matched groups: (1) seven hospitalized patients with HIV and SARS-CoV-2 coinfection, (2) seven people living with HIV (PLWH) who tested negative for SARS-CoV-2, and (3) seven healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the differentially expressed proteins (DEPs).ResultsWe quantified 5,373 proteins across 21 samples and identified significant alterations in multiple proteins in people living with HIV (PLWH) with COVID-19 compared to both PLWH and healthy controls. These DEPs were associated with inflammatory responses, immune cell migration, degranulation, and, notably, the complement and coagulation cascades. In addition, we identified DEPs associated with SARS-CoV-2 infection, including viral receptors, proteases, transcription factors, and kinases.ConclusionsThe proteomic profile highlighted the disruption caused by COVID-19 in immunomodulation, thrombosis, and viral entry pathways in PLWH. Further validation of these signatures could improve risk stratification and tailored interventions for this vulnerable patient cohort.
Objective: To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. Methods: Patients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analysed using the Stanford University HIV Drug Resistance Database. Results: Six HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with antiretroviral therapy duration of >= 3 y who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, P < 0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new-generation NNRTIs in patients with CRF08_BC; doravirine (r = 1.0), rilpivirine (r = 0.93), and etravirine (r = 0.86) resistance highly correlated with efavirenz/nevirapine. Conclusions: The present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
Mycobacterium infections are prevalent among individuals with HIV. Conventional diagnostic techniques, such as smear microscopy and culture, exhibit low sensitivity and are time-intensive, while GeneXpert technology, although more advanced, incurs significant economic costs. Present diagnostic approaches predominantly depend on specimen collection from the site of infection, primarily through sputum samples, which presents a notable limitation. Therefore, there is an urgent need for the development of novel biomarkers to enhance the diagnosis of Mycobacterium infections in the HIV-infected population. This study sought to investigate aberrant exosomal miRNA profiles through the application of miRNA high-throughput sequencing, with the objective of identifying more precise molecular biomarkers for Mycobacterium infection in HIV patients. Exosomes were isolated from the plasma of HIV patients infected with Mycobacterium and from negative control subjects, and their presence was confirmed through electron microscopy, nanoparticle tracking analysis, and Western blotting. The miRNA content of these exosomes was profiled using high-throughput sequencing. The expression levels of selected plasma exosomal miRNAs were subsequently validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). To assess the diagnostic potential of the selected miRNAs,a receiver operating characteristic (ROC) curve was constructed. High-throughput sequencing data indicate an elevation of plasma exosomal miRNA let-7c-5p in HIV patients co-infected with Mycobacterium. This finding was corroborated by qRT-PCR, which demonstrated a significant upregulation of plasma exosomal miRNA let-7c-5p in this patient cohort. The ROC curve analysis yield an area under the curve(AUC) value of 0.9625 for exosomal miRNA let-7c-5p.The optimal cut-off value for the miRNA expression was determined to be 9.736, with corresponding sensitivity and specificity values of 90
This study aimed to evaluate the efficacy and safety of dolutegravir plus lamivudine (DTG/3TC) in antiretroviral treatment (ART)-experienced people living with HIV (PLWH). A total of 303 PLWH in Shanghai, China, who switched from triple ART to DTG/3TC between January 2019 and June 2022, with a minimum ART duration of 6 months, were retrospectively enrolled. More than 95
The study aimed to analyze changes in the clinical and epidemiological aspects of HIV-associated cryptococcal meningitis (CM) patients and to identify factors influencing their prognosis. Clinical data of patients with HIV-associated CM treated in Shanghai, China between 2013 and 2023 were collected. This study included 279 cases, 2.89% of AIDS patients, showing a yearly decrease in CM prevalence among AIDS patients (p < 0.001). Overall mortality was 10.39% with rates declining from a 2013 peak of 15.38% to 0% in 2023 despite no significant temporal pattern (p = 0.265). Diagnosis took an average of 18 ± 1 days post-symptoms, and admission CD4 counts averaged 29.2 ± 2.5 cells/μL, hinting at a non-significant decline. Frequent symptoms included fever (62.4%), headache (61.6%), fatigue (44.1%), and appetite loss (39.8%), with younger patients more likely to initially show signs of meningeal irritation. Logistic regression analysis underscored the prognostic importance of cerebrospinal fluid (CSF) white blood cell (WBC) count and procalcitonin levels. Over the decade spanning from 2013 to 2023, the incidence and mortality rates of CM among AIDS patients exhibited a downward trend. The average duration from the onset of CM to confirmation of diagnosis remained prolonged. CSF WBC count and procalcitonin levels were associated with unfavorable outcomes.