Clinical significance and management of low-level HIV viremia in the era of integrase strand transfer inhibitors.

BACKGROUND: People living with HIV (PLWH) and receiving antiretroviral therapy (ART) have a goal of achieving and maintaining viral suppression; however, the existence of PLWH that show events of low-level viremia (LLV) between 50 and 1000 copies/mL and with different virological consequences have been observed. Moreover, some reports indicate that LLV status can lead to residual immune activation and inflammation, leading to a higher occurrence of non-AIDS-defining events (nADEs) and other adverse clinical outcomes. Until now, however, published data have shown controversial results that hinder understanding of this phenomenon's actual cause(s) and origin(s). Integrase strand transfer inhibitors (INSTIs)-based therapies could lead to lower LLV over time and, therefore, more effective virological control. OBJECTIVES: This review aims to assess recent findings to provide a view of the clinical significance and management of low-level HIV viremia in the era of INSTIs.

Brain abscess caused by Nocardia farcinica in a person living with HIV.

Nocardia farcinica is the most pathogenic Nocardia, which is easy to disseminate. It can be caused by trauma, and even lead to severe lung or central nervous system infection. This report covers a case of Nocardia brain abscess in an HIV patient, who underwent resection of the brain abscess, followed by anti-infective therapy with sulfamethoxazole and meropenem, and eventually made a good recovery. The mortality rate of Nocardia farcinica brain abscess has been attributed to the severity of the underlying disease, the difficulty in identifying the pathogen, and its inherent resistance to antibiotics, leading to inappropriate or late initiation of treatment. Medication should follow the principle of sufficient dosage and sufficient course of treatment.

Osteoarticular infection caused by Talaromyces Marneffei and Salmonella in a person living with HIV: a case report.

INTRODUCTION: Talaromycosis is a common invasive fungal disease in patients with HIV. However, its association with bone destruction is unusual in AIDS patients with talaromycosis. CASE PRESENTATION: This report covers the case of a 38-year-old male AIDS patient coinfected with Talaromyces marneffei and Salmonella. The case, which involved bone destruction, was identified via metagenomic next-generation sequencing (mNGS). Following treatment with a combination of amphotericin B and piperacillin-tazobactam, the patient's elbow motion noticeably improved. Imaging findings revealed that the progression of bony destruction had halted. CONCLUSION: Bone damage due to Talaromyces marneffei infection is infrequent in HIV-positive patients. Therefore, healthcare professionals must be vigilant for potential bone lesions associated with this type of infection. Prompt diagnosis and antimicrobial treatment are crucial.

Disseminated Mycobacterium thermoresistibile Infection presented with Lymphadenectasis in an AIDS patient: case report and review of literature.

BACKGROUND: Nontuberculous mycobacteria disease is a common invasive infectious disease in patients with HIV. However, Mycobacterium thermoresistibile association with lymphadenectasis is unusual in AIDS patients. CASE PRESENTATION: This report covers the case of a 25-year-old male AIDS patient infected with Mycobacterium thermoresistibile. The case was identified via pathogen-targeted next-generation sequencing (ptNGS). CONCLUSION: This is the first report of disseminated M. thermoresistibile infection presented with lymphadenectasis in an AIDS patient. Prompt diagnosis and antimicrobial treatment are crucial.

Intelligent Fault Diagnosis of Rolling Bearings Based on a Complete Frequency Range Feature Extraction and Combined Feature Selection Methodology.

The utilization of multiscale entropy methods to characterize vibration signals has proven to be promising in intelligent diagnosis of mechanical equipment. However, in the current multiscale entropy methods, only the information in the low-frequency range is utilized and the information in the high-frequency range is discarded. In order to take full advantage of the information, in this paper, a fault feature extraction method utilizing the bidirectional composite coarse-graining process with fuzzy dispersion entropy is proposed. To avoid the redundancy of the full frequency range feature information, the Random Forest algorithm combined with the Maximum Relevance Minimum Redundancy algorithm is applied to feature selection. Together with the K-nearest neighbor classifier, a rolling bearing intelligent diagnosis framework is constructed. The effectiveness of the proposed framework is evaluated by a numerical simulation and two experimental examples. The validation results demonstrate that the extracted features by the proposed method are highly sensitive to the bearing health conditions compared with hierarchical fuzzy dispersion entropy, composite multiscale fuzzy dispersion entropy, multiscale fuzzy dispersion entropy, multiscale dispersion entropy, multiscale permutation entropy, and multiscale sample entropy. In addition, the proposed method is able to identify the fault categories and health states of rolling bearings simultaneously. The proposed damage detection methodology provides a new and better framework for intelligent fault diagnosis of rolling bearings in rotating machinery.

A novel U-shaped relationship between mitochondrial mass and risk of incomplete immune reconstitution in HIV-infected patients on antiviral therapy.

Mitochondrial mass (MM) is considered an essential parameter of the immune system, but the association of MM with incomplete immune reconstitution (IIR) in people living with HIV (PLWH) remains unclear. Here, we tested 2148 blood samples from 1999 PLWH by flow cytometry in China between August 2021 and February 2022. A novel U-shaped relationship, determined by multivariable smooth curve fitting and piecewise-linear mixed-effect model, was observed between the ratio of MM to SD (MM/SD) and IIR, with a threshold cutoff of 2.8. For MM/SD <2.8, per SD increment of MM was independently associated with 30%, 30%, 20%, and 20% decreased risk of CD4+ T-cell counts <500 cells/µL after 4 years of treatment and CD4+ T-cell counts <350 cells/µL after 4, 5, 6 years of treatment, respectively. Our study suggested that increasing MM may indicate the low risk of IIR for PLWH with MM/SD <2.8.

Progressive multifocal leukoencephalopathy in an HIV patient was diagnosed by 3 times lumbar punctures and 2 times brain biopsies.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by JC virus (JCV) and is difficult to diagnose. We report on a male HIV-positive patient with PML finally diagnosed by 3 times lumbar punctures and 2 times brain biopsies. Negative results of JCV-PCR in cerebrospinal fluid (CSF) do not rule out the diagnosis of PML when clinical manifestations and neuroimaging features suspected PML. It is necessary to obtain new CSF and make repeat tests and even perform brain biopsy.

Difficulty in diagnosing intracranial infection caused by Mycobacterium avium in an AIDS patient: case report and review of the literature.

BACKGROUND: Mycobacterium avium complex (MAC) is an uncommon clinical pathogen, especially in the central nervous system (CNS), and carries a poor prognosis. MAC infections commonly present as immune reconstitution disease (IRD) in HIV patients. Herein, we report a case of intracranial infection caused by MAC in an AIDS patient without disseminated MAC (DMAC) and immune reconstitution inflammatory syndrome (IRIS). CASE PRESENTATION: A 31-year-old HIV-positive male presented us with progressively worsening CNS symptoms, and neuroimaging revealed ring-enhancing lesions. The intracranial lesions worsened after the empirical therapy for toxoplasma encephalitis and fungal infection. Due to the rapid progression of the disease, the patient died. Mycobacterium avium was the only pathogen in brain tissue after cultures and molecular biology tests. CONCLUSION: MAC infection in CNS is challenging to diagnose in HIV patients. Our findings emphasize that obtaining tissue samples and applying molecular biology methods is essential to help diagnose the patient as soon as possible to receive adequate treatment.

Consumers' risk perception, market demand, and firm innovation: Evidence from China.

Major product safety incidents often cause widespread concern among consumers, and these product safety incidents will stimulate consumers' psychology, change their risk perception, and affect the demand for products and services of risk consumers. The change in consumer demand will eventually lead to a change in firm innovation decisions. Using Chinese firm-level data, this paper employs the news reporting of the Bawang event as a quasi-natural experiment to study the impact of risk perception changes on innovation. The empirical results of this study show that increasing consumers' risk perception caused by the negative news coverage of defective products motivates firms to increase their innovation. The effects are heterogeneous, where firms with private ownership and in developed regions are more likely to increase innovation activities. This study suggests that the relationship between consumers' risk perception and firm innovation is primarily driven by market demand. Moreover, the positive effects of risk perception on innovation are more prominent for downstream firms and those having a smaller technological distance.

Coinfection of Cytomegalovirus, Pneumocystis jirovecii pneumonia, COVID-19, and Mycobacterium colombiense in an AIDS patient: A case report.

We present an AIDS patient coinfected with Cytomegalovirus, Pneumocystis jirovecii pneumonia, nontuberculous mycobacteria, and COVID-19, who finally recovered from the coinfection. The 36-year-old man had two hospitalizations. In the first hospitalization, the patient was diagnosed with Cytomegalovirus, Pneumocystis jirovecii pneumonia, HIV, and COVID-19 quickly and accurately, and the corresponding treatment worked well. The second hospitalization can be divided into four stages: (1) Persistent fever period; (2) Persistent fever and Pulmonary Progression; (3) ICU period; and (4) Pneumothorax period. During the second hospitalization, the diagnosis of Mycobacterium colombiense was hard because the NGS, acid-fast bacilli, and culture of vomit, sputum, and bronchoalveolar lavage fluid were all negative. Still, we detected acid-fast bacilli in the blood mycobacterium culture. In conclusion, we report a severe pneumonia AIDS patient coinfected with Cytomegalovirus, Pneumocystis jirovecii pneumonia, COVID-19, and Mycobacterium colombiense who finally recovered from the disease. Nontuberculous mycobacteria infection is common in HIV patients, but bronchoalveolar lavage fluid NGS cannot identify nontuberculous mycobacteria in our report. Traditional blood culture was useful in detecting acid-fast bacilli in our study and then detecting the pathogens with NGS. Combining traditional microbial culture and emerging rapid NGS methods is more conducive to clinical diagnosis and treatment.

Swollen Necrotic Lymphadenitis Infected with Mycobacterium Paracondontium in an AIDS Patient: a Case Report and Literature Review.

Background: Non-tuberculous mycobacteria (NTM) are a group of mycobacteria that are commonly found in the environment and can cause disease in humans. The symptoms of NTM infection can be similar to those of tuberculosis, making diagnosis challenging. The morbidity associated with NTM is increasing, and clinical management can be challenging. Case Description: This report details the case of a 32-year-old male who was found to have multiple enlarged and partially necrotic lymph nodes in the neck, axilla, mediastinum, and retroperitoneum. The causative agent was rapidly identified as Mycobacterium paracondontium through pathogen-targeted sequencing (tNGS). After two weeks of treatment with azithromycin, moxifloxacin, rifabutin, and amikacin, the patient's uncomfortable symptoms had resolved, and he is currently undergoing further review. Conclusion: It is imperative that clinicians remain vigilant for the presence of NTM, particularly those that are rare, given their pervasiveness in the environment. Prompt diagnosis is of paramount importance, and molecular identification techniques represent a crucial tool in this regard. In vitro drug sensitivity testing should be conducted whenever feasible to guarantee the administration of an efficacious treatment regimen.

Development and Evaluation of a Nomogram for Predicting the Outcome of Immune Reconstitution Among HIV/AIDS Patients Receiving Antiretroviral Therapy in China.

This study aims to develop and evaluate a model to predict the immune reconstitution among HIV/AIDS patients after antiretroviral therapy (ART). A total of 502 HIV/AIDS patients are randomized to the training cohort and evaluation cohort. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis are performed to identify the indicators and establish the nomogram for predicting the immune reconstitution. Decision curve analysis (DCA) and clinical impact curve (CIC) are used to evaluate the clinical effectiveness of the nomogram. Predictive factors included white blood cells (WBC), baseline CD4+ T-cell counts (baseline CD4), ratio of effector regulatory T cells to resting regulatory T cells (eTreg/rTreg) and low-density lipoprotein cholesterol (LDL-C) and are incorporated into the nomogram. The area under the curve (AUC) is 0.812 (95% CI, 0.767∼0.851) and 0.794 (95%CI, 0.719∼0.857) in the training cohort and evaluation cohort, respectively. The calibration curve shows a high consistency between the predicted and actual observations. Moreover, DCA and CIC indicate that the nomogram has a superior net benefit in predicting poor immune reconstitution. A simple-to-use nomogram containing four routinely collected variables is developed and internally evaluated and can be used to predict the poor immune reconstitution in HIV/AIDS patients after ART.

Mental health disparities in people living with human immunodeficiency virus: A cross-sectional study on physician-patient concordance and treatment regimens.

BACKGROUND: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown. METHODS: A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen's kappa test was used to assess the agreement between physicians and PLWH. RESULTS: The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% (P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis (P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). CONCLUSION: Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

Diagnostic Value of SAA Levels and Perianal Symptoms in the Complicated Perianal Abscesses Among Mpox-Infected Patients.

Objective: Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA. Methods: A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses. Results: A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001). Conclusion: The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population.

A Case of Kaposi's Sarcoma Associated with Disseminated AIDS: The Management Challenges.

Background: As a malignant tumor derived from vascular endothelial cells, Kaposi's sarcoma (KS) is quite common in AIDS patients. Nonspecific clinical symptoms often lead to timely diagnosis or wrong treatment, leading to recurrent disease and poor prognosis. Anti-retroviral therapy (ART) could significantly reduce its morbidity and aggressiveness. As one of the ARTs, liposome anthracyclines are the preferred chemotherapy regimen for disseminated KS with multiple organs or tissue invasion. The curative effect is highly related to the degree of immunosuppression. This is the first case of AIDS with Kaposi's sarcoma, who was cured after ART and two consecutive chemotherapy with doxorubicin liposome without recurrence. This case may provide new ideas and methods for the clinical management of AIDS with Kaposi's sarcoma. Case Description: The patient, a male aged 60 years, was hospitalized on 21/11/2018 following having a cough, expectoration, and difficulty breathing. He was infected with HIV eight years ago and presented symptoms of blood-stained sputum. The patient complained that he had not received ART before. After admission, he was diagnosed as KS with disseminated AIDS after multiple biopsies and histopathological examinations. The patient was treated with ten months of ART (lamivudine+tenofovir+dolutegravir) and 14 times of chemotherapy with doxorubicin liposome (20 mg/m2, three times per week, seven times per course of treatment). The patient's disease was finally alleviated, and there was no recurrence during the follow-up. Conclusion: The reconstitution of immune function and consecutive chemotherapy with doxorubicin liposome play a vital role in treating KS. In addition, for the early general symptoms of AIDS patients, such as thrombocytopenia and hemorrhagic purple papules, it is necessary to increase vigilance and obtain the results of histopathological verification as soon as possible to diagnose KS patients at an earlier stage and realize clinical intervention in time.

SceneFusion: Room-Scale Environmental Fusion for Efficient Traveling Between Separate Virtual Environments.

Traveling between scenes has become a major requirement for navigation in numerous virtual reality (VR) social platforms and game applications, allowing users to efficiently explore multiple virtual environments (VEs). To facilitate scene transition, prevalent techniques such as instant teleportation and virtual portals have been extensively adopted. However, these techniques exhibit limitations when there is a need for frequent travel between separate VEs, particularly within indoor environments, resulting in low efficiency. In this paper, we first analyze the design rationale for a novel navigation method supporting efficient travel between virtual indoor scenes. Based on the analysis, we introduce the SceneFusion technique that fuses separate virtual rooms into an integrated environment. SceneFusion enables users to perceive rich visual information from both rooms simultaneously, achieving high visual continuity and spatial awareness. While existing teleportation techniques passively transport users, SceneFusion allows users to actively access the fused environment using short-range locomotion techniques. User experiments confirmed that SceneFusion outperforms instant teleportation and virtual portal techniques in terms of efficiency, workload, and preference for both single-user exploration and multi-user collaboration tasks in separate VEs. Thus, SceneFusion presents an effective solution for seamless traveling between virtual indoor scenes.

Neuropsychiatric Adverse Events Following Antiretroviral Therapy in People Living with HIV: A Real-World Study of Dynamic Trends and Risk Factors in Hangzhou, China.

Purpose: Neuropsychiatric adverse events (NPAEs) occur frequently in people living with human immunodeficiency virus (PLWH) receiving antiretroviral therapy (ART). This study aimed to assess the dynamic trends and risk factors of NPAEs among PLWH in Hangzhou taking efavirenz (EFV)- or dolutegravir (DTG)- or elvitegravir (EVG)-based regimens. Patients and Methods: A total of 287 ART-naive PLWH were included in this study, EFV (400mg)- (n = 122), EFV (600mg)- (n = 37), DTG- (n = 73), EVG-based (n = 47) and other ART regimens (n = 8) as the initial ART regimen were administered for 12 months. All data were collected at five time points within a 12-month follow-up. The Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale were used to evaluate sleep disorders and anxiety and depression symptoms, respectively. The dynamic trends and potential risk factors of NPAEs were investigated using a generalized linear mixed model. Results: Mean age was 29.4 (SD: 7.5) years with 97.2% males. After 12 months of ART, the prevalence of sleep disorders and anxiety decreased significantly, although only a slight improvement was observed for depression. In addition, there was a significant positive correlation between sleep disorders, anxiety, and depression. The risk factors for NPAEs differed slightly depending on the choice of ART regimen, but the seven factors most commonly associated with NPAEs were age, sex, marital status, education level, smoking status, body mass index, and WHO clinical stage. Treatment-induced changes in CD4-positive T-cell count and virological suppression did not depend on the particular choice of ART regimen. Conclusion: The prevalence of sleep disorders and anxiety changed significantly over time on ART and the risks of these disorders were associated with seven common clinical and demographic factors.

Case Report: A case of Chlamydia psittaci infection in an HIV patient.

Chlamydia psittaci is the pathogen of psittacosis and infects a wide range of birds and even humans. Human infection occurs most commonly in those with a history of contact with birds or poultry. We describe a case of psittacosis in a human immunodeficiency virus infected patient in Zhejiang Province for the first time. C. psittaci infection was confirmed by nested polymerase chain reaction (PCR) and Real-Time PCR. Phylogenetic analysis revealed that the sequences from the patient's samples clustered with genotype A in the same branch. Our study highlights the possibility of diagnosing psittacosis in patients with a chronic disease such as HIV-infected patients, and should increase awareness and surveillance of psittacosis in China.

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection is characterized not only by severe immunodeficiency but also by persistent inflammation and immune activation. These characteristics persist in people living with HIV (PLHIV) receiving effective antiretroviral therapy (ART) and are associated with morbidity and mortality in nonacquired immunodeficiency syndrome (AIDS) events. ART can inhibit HIV replication and promote immune reconstitution, which is currently the most effective way to control AIDS. However, despite effective long-term ART and overall suppression of plasma HIV RNA level, PLHIV still shows chronic low-level inflammation. The exact mechanisms that trigger chronic inflammation are unknown. Activation of the inflammasome is essential for the host response to pathogens, and some recent studies have confirmed the role of the inflammasome in the pathogenesis of inflammatory diseases. The NLRP3 inflammasome has been widely studied, which is a pyrin domain-containing protein 3 belonging to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent studies suggest that inflammasome-mediated pyroptosis is associated with CD4+ T cell loss in the absence of persistent infectious HIV replication. This article reviews the mechanism of the NLRP3 inflammasome and its correlation with immune reconstitution in PLHIV treated with ART.

Treg Cell Evaluation in Patients with Acquired Immune Deficiency Syndrome with Poor Immune Reconstitution and Human Immunodeficiency Virus-Infected Treg Cell Prevention by Polymeric Nanoparticle Drug Delivery System.

To better deliver antiretroviral drugs for treating patients with acquired immune deficiency syndrome (AIDS) with poor immune reconstitution, a novel nanopole capsule was designed in this study. Forty-eight patients with AIDS with poor immune reconstitution were chosen as subjects to test their immune state. CD4+ T and Regulatory T cells (Treg) infected with HIV were cultured to test polyethyleneimine (PEI) and polychitosan (PC) drug delivery system efficiency. The infiltration efficiency test was performed to study the drug delivery efficiency of the delivery systems, and the cell numbers of CD4+ T and Treg cells infected with HIV were calculated to evaluate the therapeutic effect. The results showed that patients with AIDS with poor immune reconstitution had lower CD4+ T cell count and higher Treg cell count. Furthermore, the infiltration efficiency of the PC drug delivery system was higher than that of the PEI drug delivery system, and the therapy efficiency of antiretroviral drugs was greatly improved in the PC group. Additionally, the improvement of CD4+ T and Treg cells damaged by HIV was greater in the PC group. Sequentially, the PC system can better deliver and release loaded antiretroviral drugs and may be a better choice for treating patients with AIDS with poor immune reconstitution in the future.