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Background: We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen. Methods: This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18-65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605. Findings: Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI -1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD -0.90 kg, 95% CI, -1.43 to -0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF. Interpretation: In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF. Funding: Jiangsu Aidea Pharmaceutical & the National "Thirteenth Five-year Period" Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology.
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The modulation of the chemical microenvironment surrounding metal nanoparticles (NPs) is an effective means to enhance the selectivity and activity of catalytic reactions. Herein, a post-synthetic modification strategy is developed to modulate the hydrophobic microenvironment of Ru nanoparticles encapsulated in a metal-organic framework (MOF), MIP-206, namely Ru@MIP-Fx (where x represents perfluoroalkyl chain lengths of 3, 5, 7, 11, and 15), in order to systematically explore the effect of the hydrophobic microenvironment on the electrocatalytic activity. The increase of perfluoroalkyl chain length can gradually enhance the hydrophobicity of the catalyst, which effectively suppresses the competitive hydrogen evolution reaction (HER). Moreover, the electrocatalytic production rate of ammonia and the corresponding Faraday efficiency display a volcano-like pattern with increasing hydrophobicity, with Ru@MIP-F7 showing the highest activity. Theoretical calculations and experiments jointly show that modification of perfluoroalkyl chains of different lengths on MIP-206 modulates the electronic state of Ru nanoparticles and reduces the rate-determining step for the formation of the key intermediate of N2H2 *, leading to superior electrocatalytic performance.
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Integrase strand transfer inhibitors (INSTIs) in anti-retroviral therapy (ART) have been recommended by the World Health Organization for their higher efficacy, favorable safety and tolerability. However, the clinical evidence supporting switching to INSTI-containing regimens in low-and-middle-income countries (LMICs) is limited, as few patients have access to these regimens. We aimed to assess the effectiveness of INSTI-containing regimens in real-world settings in China compared to government-provided free ART. We compared the short-term (first 4 mo following ART initiation) and long-term (1 year after ART initiation) effectiveness between INSTI-containing regimens and free ART drugs provided by the Chinese government in 4 dimensions: viral suppression status, immune response, liver and kidney function, and AIDS-related diseases. We obtained data from electronic medical records in the National Infectious Disease Surveillance System. To control baseline confounders, we used propensity score matching (PSM), calculated using logistic regression including socio-demographic and baseline factors. Among 12,836 patients from 2012 to 2019, 673 (5.2%) used INSTI-containing regimens. Patients with INSTI-containing regimens were matched to those with free drugs (644 vs 644). For short-term effectiveness, patients initiating INSTI-containing regimens were more likely to achieve viral suppression (81.4% vs 52.0%; Pâ <â .001). The differences in immune response, liver and kidney function and AIDS-related diseases were not significant between the 2 groups. For long-term effectiveness, viral suppression rates were similar (87.96% vs 84.59%; Pâ =â .135), with no significant differences in immune response, liver and kidney function, or AIDS-related diseases. Our study suggests that patients initiating ART with INSTI-containing regimens have worse physical status at baseline than patients starting with free ART drugs. Furthermore, we found better virological performances of INSTI-containing regimens in the short-term but not in the long-term due to a high rate of drug changes. Our findings have clinical implications and provide new evidence regarding the effectiveness of INSTI-containing regimens in LMICs.
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Infecções por HIV , Inibidores de Integrase de HIV , Humanos , Masculino , Feminino , Estudos Retrospectivos , China/epidemiologia , Adulto , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Pessoa de Meia-Idade , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Resultado do TratamentoRESUMO
AIMS: This study aimed to explore the mediating effect of self-management (SM) on the relationship between illness perception and quality of life (QOL) among Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). DESIGN: A cross-sectional study. METHODS: We explored the effect of illness perception and self-management on QOL using the multiple regression model. Moreover, we conducted a simple mediation analysis to examine the role of SM in the relationship between illness perception and QOL. In addition, a parallel mediation analysis was performed to investigate the differences in domains of SM on the relationship between illness perception and QOL. RESULTS: Among 300 Chinese HIV-positive MSM, the mean score of SM was 39.9 ± 6.97, with a range of 14.0-54.0. The higher score in SM indicated a higher level of HIV SM. SM was negatively related to illness perception (r = -0.47) while positively related to QOL (r = 0.56). SM partially mediated the relationship between illness perception and QOL, accounting for 25.3% of the total effect. Specifically, both daily self-management health practices and the chronic nature of the self-management domain played a parallel role in mediating the relationship between illness perception and QOL. CONCLUSION: Our study demonstrated that SM was a significant factor influencing QOL among HIV-positive MSM. Focusing on daily self-management health practices and the chronic nature of self-management could be the potential key targets for enhancing HIV self-management strategies. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study emphasized the role of SM in the well-being of HIV-positive MSM and underscored the importance of developing interventions that integrate SM strategies to improve QOL in this population. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Near-field enhanced mid-infrared light-matter interactions via metallic plasmonic antennae (PA) have attracted much attention but are inevitably limited by the detuning between their narrow band and the broad applied spectral range. Here, we develop a new low-temperature incubation synthetic method to acquire uniform Ag microparticles (MPs) with numerous hotspots. Their plasmonic band is remarkably extended by the plasmonic coupling of numerous hotspots and covers the entire mid-infrared range (400-4000 cm-1). Hence, the almost complete molecular fingerprint of 4-mercaptobenzonitrile was successfully probed for the first time via resonant surface-enhanced infrared absorption (rSEIRA), and the rSEIRA spectra of different essential amino acids were further detected and exhibit a high spectral identification degree assisted by machine learning. This work changes the inertia perception of "narrow band and large size but small hotspot area" of mid-infrared metallic PA and paves the way for the ultrasensitive mid-infrared optical sensing.
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Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.
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COVID-19 , Microbioma Gastrointestinal , Trombose , Humanos , Camundongos , Animais , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Colágeno/metabolismo , Plaquetas/metabolismo , COVID-19/metabolismoRESUMO
Functional nanomaterials involve various nanostructured objects, such as zero-dimensional (0D), 1D, and 2D nano-objects (nanoparticles, nanowires, nanotubes, nanosheets, etc [...].
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BACKGROUND: Existing research has provided evidence of changes in hepatitis delta virus (HDV) prevalence worldwide. This study aimed to investigate the prevalence and molecular characteristics of HDV to elucidate its spread in China. METHODS: A total of 3,000 samples were collected from 2,241 HBV monoinfections and 759 HBV/HIV-1 coinfections across 13 sites in northern, southern, western, and southwestern China. Serological and virological prevalence were determined by detecting anti-HDV antibodies and HDV RNA. RESULTS: The study revealed a 2.63% (95% CI: 2.06-3.21) seroprevalence of HDV among HBV infections in China, exhibiting regional variation. HDV seroprevalence was notably higher at 7.91% (95% CI: 5.98-9.83) in HBV and HIV-1 coinfections. Region and HIV-1 infection were identified as risk factors for HDV infection. Virological prevalence was 0.67% (95% CI: 0.38-0.96) in HBV infections and 2.24% (95% CI: 1.18-3.29) in HBV/HIV-1 coinfections. The predominant HDV genotype in China was HDV-2a, followed by HDV-1. Participants with anti-HDV positivity demonstrated significantly higher proportions of abnormal liver dysfunction and elevated HBV DNA load (P < 0.001) compared to anti-HDV-negative participants. CONCLUSIONS: This study highlights the HDV epidemic in China, sheds light on its geographical distribution and high-risk populations, and provides insights for developing strategies to manage the spread of HDV in the country.
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Coinfecção , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Antígenos de Superfície da Hepatite B , Vírus Delta da Hepatite/genética , Prevalência , Estudos Soroepidemiológicos , Coinfecção/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , China/epidemiologia , Vírus da Hepatite B/genéticaRESUMO
BACKGROUND: Talaromycosis is one of the most common opportunistic infections in human immunodeficiency virus (HIV) infected patients. However, few researches have explored the prevalence in Southern China and fully assessed the value of the Mp1p antigen screening for the diagnosis of talaromycosis. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional study of HIV-infected antiretroviral therapy (ART)-naïve adult patients who were seen in 2018 at Guangzhou Eighth People's Hospital, Guangzhou Medical University. Serum samples collected from all the 784 enrolled patients were tested for Mp1p antigen using double-antibody sandwich enzyme-linked immunosorbent assay. A culture of pathogen was conducted in 350 clinically suspected patients to confirm talaromycosis. The overall prevalence of talaromycosis based on the Mp1p antigen detection was 11.4% (89/784) and peaked at 32.2% (75/233) in patients with CD4+ ≤50 Nr/µl. Logistic regression analysis found Mp1p antigen positive rate decreased with the increase in CD4+ counts (OR 0.982, 95% CI 0.977-0.987, P<0.01). The optimal cut-off point of the CD4+ count was 50 Nr/µl or less. Among the 350 patients received both fungal culture and Mp1p antigen detection, 95/350 (27.1%) patients were culture-positive for a Talaromyces marneffei, 75/350 (21.4%) patients were Mp1p antigen positive. The Mp1p antigen assay showed a good agreement to the culture of pathogen, and the sensitivity, specificity, positive predictive value, negative predictive value and kappa value was 71.6% (68/95), 97.3% (248/255), 90.7% (68/75), 90.2% (248/275), and 0.737, respectively. The screening accuracy of the Mp1p antigen assay in patients with CD4+ counts of ≤50 Nr/µl was superior to that in those with higher CD4+ counts. CONCLUSIONS/SIGNIFICANCE: Mp1p antigen screening can be an effective tool for more efficient diagnosis of Talaromycosis, especially in HIV/AIDS patients with low CD4+ counts. Future validation studies are needed.
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Infecções por HIV , Micoses , Adulto , Humanos , HIV , Estudos Transversais , Micoses/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Contagem de Linfócito CD4RESUMO
The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein-peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient's recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease.
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BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS: Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
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Coinfecção , Infecções por HIV , Hepatite B Crônica , Masculino , Humanos , Adulto , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Infecções por HIV/tratamento farmacológico , HIV , DNA Viral , Incidência , Coinfecção/tratamento farmacológico , Estudos Retrospectivos , Tenofovir/uso terapêutico , Lamivudina/uso terapêutico , Hepatite B Crônica/tratamento farmacológicoRESUMO
OBJECTIVE: To determine plasma exosomal circular RNA LPAR1 (circLPAR1) expression in gastric cancer (GC) and analyze its clinical value in GC diagnosis and prognosis evaluation. METHODS: The research subjects were 64 GC patients, 30 chronic gastritis (CG) patients (disease control group) and 30 healthy controls (HCs; healthy control group). RT-PCR quantified circLPAR1 expression in GC tissues and adjacent counterparts of GC patients as well as plasma exosomal circLPAR1 in each group. The correlation of differentially expressed circLPAR1 with clinicopathological indexes was analyzed, and receiver operating characteristics (ROC) and Kaplan-Meier curves were drawn to evaluate the value of plasma exosomal circLPAR1 in GC diagnosis and prognosis assessment. RESULTS: GC patients exhibited lower plasma exosomal circLPAR1 levels than CG patients and HCs (P<0.05). Lower circLPAR1 expression was determined in GC tissues than in adjacent counterparts (P<0.05), and a positive connection between GC tissue circLPAR1 and plasma exosomal circLPAR1 was identified in GC patients (P<0.05). Evidently elevated plasma exosomal circLPAR1 was observed in post-surgical GC patients (P<0.05). ROC curves showed that the areas under the curve (AUCs) of plasma exosomal circLPAR1, serum carcinoembryonic antigen (CEA), and serum carbohydrate antigen 19-9 (CA19-9) for the diagnosis of GC were 0.836, 0.767 and 0.746, respectively, and the AUC of their combined diagnosis was 0.914. Low plasma exosomal circLPAR1 was strongly linked to tumor size, differentiation degree, tumor-node-metastasis (TNM) staging, vascular invasion, lymphatic metastasis, and HER2 expression of GC patients (P<0.05). GC patients with high plasma exosomal circLPAR1 expression had significantly longer prognostic survival time than those with low expression (P<0.05). According to univariate and multivariate Cox regression analyses, tissue differentiation degree (HR=1.415), TNM stage (HR=1.637), HER2 expression (HR=1.831), and low plasma exosomal circLPAR1 expression (HR=2.042) were risk factors for adverse prognosis in GC patients. CONCLUSIONS: circLPAR1 expression is related to GC progression, and the detection of plasma exosomal circLPAR1 has promising clinical application value in assisting the diagnosis and prognosis evaluation of GC.
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Latent viral reservoir is recognized as the major obstacle to achieving a functional cure for HIV infection. We previously reported that arsenic trioxide (As2O3) combined with antiretroviral therapy (ART) can reactivate the viral reservoir and delay viral rebound after ART interruption in chronically simian immunodeficiency virus (SIV)-infected macaques. In this study, we further investigated the effect of As2O3 independent of ART in chronically SIV-infected macaques. We found that As2O3-only treatment significantly increased the CD4/CD8 ratio, improved SIV-specific T cell responses, and reactivated viral latency in chronically SIVmac239-infected macaques. RNA-sequencing analysis revealed that As2O3 treatment downregulated the expression levels of genes related to HIV entry and infection, while the expression levels of genes related to transcription initiation, cell apoptosis, and host restriction factors were significantly upregulated. Importantly, we found that As2O3 treatment specifically induced apoptosis of SIV-infected CD4+ T cells. These findings revealed that As2O3 might not only impact viral latency, but also induce the apoptosis of HIV-infected cells and thus block the secondary infection of bystanders. Moreover, we investigated the therapeutic potential of this regimen in acutely SIVmac239-infected macaques and found that As2O3 + ART treatment effectively restored the CD4+ T cell count, delayed disease progression, and improved survival in acutely SIV-infected macaques. In sum, this work provides new insights to develop As2O3 as a component of the "shock-and-kill" strategy toward HIV functional cure. IMPORTANCE Although antiretroviral therapy (ART) can effectively suppress the viral load of AIDS patients, it cannot functionally cure HIV infection due to the existence of HIV reservoir. Strategies toward HIV functional cure are still highly anticipated to ultimately end the pandemic of AIDS. Herein, we investigated the direct role of As2O3 independent of ART in chronically SIV-infected macaques and explored the underlying mechanisms of the potential of As2O3 in the treatment of HIV/SIV infection. Meanwhile, we investigated the therapeutic effects of ART+As2O3 in acutely SIVmac239-infected macaques. This study showed that As2O3 has the potential to be launched into the "shock-and-kill" strategy to suppress HIV/SIV reservoir due to its latency-reversing and apoptosis-inducing properties.
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Background: Antiretroviral therapy (ART) efficiently reduces the morbidities and mortalities caused by HIV-1 infection and prevents the HIV epidemic. However, virologic failure (VF) occurs in some patients receiving ART experience, especially increases in those patients with intermittent or persistent low-level viremia (LLV). The presence of drug resistance mutations (DRMs) in LLV was a strong predictor of subsequent VF. The data on drug resistance (DR) or DRMs for HIV-1 infections at low-level viral load (LLVL) are limited in China. Objective: To monitor the prevalence of HIV-1 drug resistance and to evaluate the risk factors associated with drug resistance in LLVL HIV-1 infections during ART in Guangdong, China. Methods: Plasma samples with LLVL during ART in Guangdong Province between Jan 2011 and Dec 2022 were subjected to a modified reverse-transcription PCR with a pre-step of virus concentration by ultracentrifugation before extraction and the Sanger sequencing. Then, the genotypic resistance test was performed and DR was analyzed by the Stanford HIVDB program. Finally, DR-associated factors were identified by logistic regression analysis. Results: We found that CRF01_AE (53.57%) and CRF07_BC (25.07%) were the dominant HIV-1 genotypes in LLVL in Guangdong between 2011 and 2022 but that the percentage of CRF01_AE showed a trend of decrease over time. M46 (1.49%), M184 (30.91%), and K103 (21.46%) were the dominant PI-, NRTI-, and NNRTI-associated mutations, respectively. The total DR rate was 47.06%. Specifically, PI (3.71%) showed a significantly lower DR rate than NNRTI (40.74%) and NRTI (34.14%). Duration of ART, initial ART regimen, ethnicity, and WHO clinical stages were associated with DR. Conclusion: The drug resistance rate among the LLVL during ART in Guangdong, China is high. The risk factors associated with HIV drug resistance should be seriously considered for better control.
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Surface-enhanced Raman scattering (SERS) is a widely used rapid and noninvasive method for detecting biological substances in serum samples and is commonly employed in disease screening and diagnosis. Solid-state nanoarray SERS substrates used in serum detection may cause spectral instability due to imperfections in the detection method. For the purpose of identifying optimal detection conditions, various dilution levels of the serum were tested in this study. The study found that a complete and stable serum SERS spectrum can be obtained when the serum is diluted by a factor of 50. The study reports the successful preparation of an Au nanocone array (Au NCA) plasmonic substrate with a uniform, controllable microstructure and high activity, achieved through a combination of PS colloidal sphere template-assisted reactive ion etching (RIE) process and magnetron sputtering deposition technology. Based on this substrate, a standard detection scheme was developed to obtain highly stable and repeatable serum SERS spectra. The study verified the reliability of the optimized serum detection scheme by comparing the SERS spectra of serum samples from healthy individuals and gastric cancer patients, and confirmed the potential benefits of the scheme for disease screening and diagnosis.
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Background: Ainuovirine (ANV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which was initially synthesized in Korea and later further developed in both Korea and China. Methods: A randomized, double-blind, double-dummy, positive parallel group, non-inferiority, phase 3 trial was conducted in 7 sites across China. Eligible HIV-1-positive antiretroviral therapy (ART)-naïve adults aged 18-65 years were randomly assigned in a 1:1 ratio to receive tenofovir disoproxil fumarate and lamivudine (TDF+3TC) in combination with either ANV (ANV group) or efavirenz (EFV group) for up to 48 weeks. Subsequently, participants in both groups received one of the two drug combinations according to their choice until week 96 in an observational study under an open-label setting. The primary endpoint was the proportion of participants achieving HIV RNA <50 copies/mL at week 48, with non-inferiority pre-specified at a margin of 10%. The secondary efficacy endpoints were logarithmic changes in HIV RNA, percentage of participants with HIV RNA levels ≤400 copies/mL and changes in the CD4 T-cell count after 48 and 96 weeks of treatment, as well as the percentage of participants with HIV RNA levels <50 copies/mL at 96 weeks of treatment. Safety endpoints were the incidence of adverse events and laboratory abnormalities evaluated according to the Division of AIDS criteria. This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019041). Findings: Between November 27, 2018 and March 11, 2021, a total of 826 participants were screened, and 630 were finally enrolled and randomly assigned (1:1) to either ANV (n = 315) or EFV (n = 315) groups. The mean age was 30.6 ± 9.4 years and most participants were male (94.6%). At week 48, 274 (87.0%) of 315 participants in the ANV group and 288 (91.7%) of 314 in the EFV group achieved HIV-1 RNA <50 copies/mL and non-inferiority was established (difference: -4.7%, 95% CI: -9.6 to 0.1%). In the period, 293 participants continued to take the ANV regimen and 287 switched from the EFV to the ANV regimen. During the open-label period, 92.5% (271/293) of participants in the continued ANV group and 95.1% (273/287) in the ANV to EFV transfer group remained virologically suppressed (HIV-1 RNA <50 copies/mL) at week 96 (p = 0.189). The incidence of NNRTI treatment-related adverse events (TEAEs) at week 48 was 67.6% in 315 participants in the ANV group, which was significantly lower than in 91.4% of 314 participants in the EFV group (p < 0.001). The most common TEAEs (weeks 0-48) were dizziness (10.5%) and dyslipidemia (22.2%) in the ANV group vs. 51.0% and 34.4% in the EFV group, respectively, followed by transaminase elevation (9.2% vs. 29.0%), γ-glutamyl transferase elevation (8.3% vs. 19.1%), and rash (7.9% vs. 18.8%) (all p < 0.001). After switching from EFV to ANV, TEAEs in the former EFV participants were significantly reduced in the following observational period of 48-96 weeks. Interpretation: The week 48 results indicated that the efficacy of ANV was non-inferior to EFV when combined with two NRTIs. The per-protocol risk difference at week 48 for the primary endpoint also supported non-inferiority. TEAEs in ANV treated participants were less frequent with regard to liver toxicity, dyslipidemia, neuropsychiatric symptoms and rash compared to the EFV group during the first 48 weeks of therapy. The effects were maintained during the 48-96 weeks of therapy. Funding: Jiangsu Aidea Pharmaceutical Co., Ltd.
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Background: The direct-acting antiviral agents (DAAs) have revolutionized the treatment of Hepatitis C Virus (HCV) infection. However, a simple and feasible treatment strategy with high efficacy and safety for HCV in patients coinfected with Human Immunodeficiency Virus (HIV) remains an unmet medical need, especially in areas with limited health resource. This study aims to assess the efficacy and safety of 12 weeks of treatment with sofosbuvir and velpatasvir in patients with chronic HCV/HIV-1 coinfection. Methods: We conducted a multicenter, single-arm, open-label study in China, which involved chronic HCV/HIV-1 coinfected patients who are receiving an antiretroviral regimen of a combination tablet consisting of elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide, (EVG/c/FTC/TAF) once daily. Patients with liver cirrhosis or experienced to DAAs treatment were excluded. All patients received combined sofosbuvir (400 mg) and velpatasvir (100 mg) tablet once daily for 12 weeks regardless of HCV genotype. The primary efficacy endpoint was sustained virologic response, defined as HCV RNA <15 IU/mL at 12 weeks after completion of treatment (SVR12). The primary safety endpoint was the proportion of patients who prematurely discontinued treatment because of adverse events. Safety and efficacy data were analyzed with an intention-to-treat (ITT) population (last observation carried forward) and per-protocol (PP) population. This trial is registered on ChiCTR.org.cn with number being ChiCTR1800020246. Findings: Of the 243 patients enrolled, 78% were male, 9% had been previously treated for HCV with interferon, and none had pre-defined cirrhosis, although 8% had Fibrosis 4 score (FIB-4) >3.25. A total of 233 patients completed 12-week post-treatment follow-up. Overall, 227/233 patients (97%) achieved SVR12: 100% (63/63) in those with HCV genotype 1, 67% (2/3) in those with genotype 2, 95% (84/88) in those with genotype 3, 99% (78/79) in those with genotype 6. Rates of SVR12 were lower among those with baseline FIB-4 >3.25 than those without (78% [14/18] vs. 99% [211/212], P < 0.001). HIV-1 suppression was not compromised. The most common adverse events were upper respiratory tract infection (5%), cough (3%), abnormal renal function (2%), abnormal liver function (2%), constipation (2%), urinary tract infection (2%) and sleep disorders (2%). No participant discontinued treatment because of adverse events or death. Interpretation: Twelve weeks of treatment with sofosbuvir/velpatasvir provide high rates of SVR and is well-tolerated in patients coinfected with HIV-1 and HCV regardless of HCV genotypes. Non-invasive liver fibrosis score may help to further distinguish patients at greater likelihood of a suboptimal response. Funding: The 13th Five Year Plan of the Ministry of Science and Technology of China for the prevention and treatment of major infectious diseases such as AIDS and viral hepatitis, the National Key Research and Development Program of China, Medical Key Discipline Program of Guangzhou-Viral Infectious Diseases (2021-2023), Basic research program on people's Livelihood Science and technology of Guangzhou, and National Natural Science Foundation of China.
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Volatile organic compounds (VOCs), particularly monoaromatic hydrocarbon compounds (MACHs), pose a potential risk to the atmospheric environment and human health. Therefore, the progressive development of efficient detection methodologies is a pertinent need, which is still a challenge at present. In this study, we present a rapid and sensitive method to detect trace amounts of MACHs using a bifunctional SERS composite substrate. We prepared an Au/SiO2 enhanced layer and a porous Cu(OH)2 adsorption layer via microfluidic-assisted gas-liquid interface self-assembly. The composite substrate effectively monitored changes in benzaldehyde using time-varying SERS spectra, and track-specifically identified various VOCs such as benzene, xylene, styrene, and nitrobenzene. In general, the substrate exhibited a rapid response time of 20 s to gaseous benzaldehyde, with a minimum detection concentration of less than 500 ppt. Further experimental assessments revealed an optimum Cu(OH)2 thickness of the surrounding adsorption layer of 150 nm, which can achieve an efficient SERS response to MACHs. Furthermore, the recoverable and reusable property of the composite substrate highlights its practicality. This study presents a straightforward and efficient approach for detecting trace gaseous VOCs using SERS, with significant implications in the designing of SERS substrates for detecting other VOCs.
RESUMO
Styrene, a prevalent volatile organic compounds (VOCs), is very harmful to atmosphere and humans. Consequently, the development of efficient detection technologies for styrene is of high importance, which is still in challenge! In this work, we crafted a layered double hydroxide (LDH) porous film-coated gold nanoarray, designed to act as a surface enhanced Raman spectroscopy (SERS) chip for the efficient and portable detection of gaseous styrene. This chip features a covering layer composed of cross-linked LDH nanosheets, notable for their porous structure and high specific surface area. When the covering layer is 100-300 nm in thickness, this composite chip has significant enrichment effect and strong SERS performance to gaseous styrene with a lowest detectable concentration below 1 ppb (4.64 ×10-3 mg/m3), and can response within 10 s, showing the rapid response and high sensitivity. Additionally, the chip has strong anti-interference capabilities and maintains excellent response to styrene, even in mixed benzene-VOCs gases. The exceptional SERS performances of this chip is ascribed to its LDH covering layer-induced styrene-enrichment and structurally-enhanced SERS performances. This study provides a simple route and practical chip for the rapid and ultrasensitive SERS-based detection of gaseous styrene, which is also potentially beneficial for the detection of other gaseous VOCs.
RESUMO
Background and aims: It is necessary to identify simple biomarkers that can efficiently predict the efficacy of long-term antiretroviral therapy (ART) against human immunodeficiency virus (HIV), especially in underdeveloped countries. We characterized the dynamic changes in plasma interleukin-18 (IL-18) and assessed its performance as a predictor of long-term virological response. Methods: This was a retrospective cohort study of HIV-1-infected patients enrolled in a randomized controlled trial with a follow-up of 144 weeks of ART. Enzyme-linked immunosorbent assay was performed to evaluate plasma IL-18. Long-term virological response was defined as HIV-1 RNA <20 copies/mL at week 144. Results: Among the 173 enrolled patients, the long-term virological response rate was 93.1%. Patients with a long-term virological response had significantly lower levels of week 24 IL-18 than non-responders. We defined 64 pg./mL, with a maximum sum of sensitivity and specificity, as the optimal cutoff value of week 24 IL-18 level to predict long-term virological response. After adjusting for age, gender, baseline CD4+ T-cell count, baseline CD4/CD8 ratio, baseline HIV-1 RNA level, HIV-1 genotype and treatment strategy, we found that lower week 24 IL-18 level (≤64 vs. >64 pg./mL, a OR 19.10, 95% CI: 2.36-154.80) was the only independent predictor of long-term virological response. Conclusion: Early on-treatment plasma IL-18 could act as a promising indicator for long-term virological response in patients with HIV-1 infection. Chronic immune activation and inflammation may represent a potential mechanism; further validation is necessary.