Purpose:This study aimed to investigate whether mutations in the rv2005c, PPE59, and recC genes are associated with fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), particularly in strains lacking mutations in the known resistance genes gyrA and gyrB. Methods:A total of 275 clinical isolates, consisting of 217 pre-extensively drug-resistant strains and 58 fluoroquinolone-sensitive strains, were included in this study. Gene sequencing was performed on all isolates, and functional assessments through both overexpression and knockout experiments of the gene were conducted to evaluate its effect on fluoroquinolone susceptibility. Results:Results: Among 275 isolates, no mutations were detected in PPE59 or recC. In the 217 pre-XDR isolates, gyrA mutations were found in 214 (98.6%), predominantly at codons 94, 90, and 91. Only two isolates harbored synonymous mutations in rv2005c (P235P), both with concurrent gyrA D94G mutations. Overexpression or knockout of rv2005c in Mtb did not alter FQ susceptibility. Notably, two FQ-resistant isolates lacked mutations in any of the five genes sequenced, suggesting the presence of unknown resistance mechanisms. Conclusion:Our results showed that mutations of the rv2005c, PPE59 and recC genes may not contribute to FQ resistance in clinical isolates of Mtb in Chongqing, China. Furthermore, our study results also showcased the complexity of mechanisms of FQ resistance in clinical Mtb isolates.

Background and Aim:As a first line anti-tuberculosis drug, isoniazid (INH) has been extensively used for decades. Consequently, resistance of Mycobacterium tuberculosis (MTB) clinical isolates to INH is inevitably increasing and spreading, necessitating fast and accurate molecular diagnosis tools. Although many previous molecular epidemiological studies related with INH resistance included mutations in the oxyR-ahpC intergenic region, the role of mutations in the oxyR-ahpC intergenic region in INH resistance remains controversial. The present study aimed to investigate the frequency and distribution of mutations in the ahpC and the oxyR-ahpC intergenic region among INH-resistant Mycobacterium tuberculosis (MTB) clinical isolates in Chongqing, China. Methods:The presence of mutations in katG, ahpC and the oxyR-ahpC intergenic region was analyzed in 490 MTB clinical isolates. Results:None of the 73 INH-susceptible isolates (0%), 18 of 26 INH mono-resistant isolates (69.2%), 188 of 199 MDR (multidrug resistant) isolates (94.5%), and 176 of 192 pre-XDR/XDR (pre-extensively drug-resistant) isolates (91.7%) had mutations in katG. No mutations in ahpC, oxyR and the oxyR-ahpC intergenic region were identified in INH-susceptible and INH mono-resistant isolates. Mutations in the oxyR-ahpC intergenic region were rare (1.5% MDR, 1.04% pre-XDR), and only two mutations were identified (-58 G→A in MDR and -54 C→T in pre-XDR isolates). The former occurred in isolates with concurrent katG mutations, but the latter occurred in isolates without concurrent katG mutations. Notably, a novel Ala18Gly mutation in oxyR was identified in 3.52% of MDR and 6.77% of pre-XDR isolates. Conclusion:Mutation in katG is the main cause of INH resistance in MTB clinical strains isolated from Chongqing. It is very unlikely that mutation in the oxyR-ahpC intergenic region alone could cause INH resistance in MTB clinical isolates. Even though mutation in the oxyR-ahpC intergenic region could compensate the fitness cost of katG mutation, our finding that it is uncommon in MTB clinical isolates from Chongqing suggests it is not the primary compensatory mechanism. Further investigation is necessary to probe the relationship between mutations in the coding region of oxyR and INH resistance.

BackgroundImmunological non-responders (INRs) and immunological responders (IRs) exhibit distinct patterns of immune reconstitution despite suppressive antiretroviral therapy (ART); however, the genetic characteristics of the HIV-1 reservoir in these groups remain poorly understood. This study investigates the landscape of HIV-1 proviruses in INRs and IRs, and its potential association with immune reconstitution.MethodsPeripheral blood mononuclear cells (PBMCs) from 10 ART-treated INRs and 10 IRs were analyzed using near-full-length HIV-1 DNA amplification and PacBio third-generation sequencing to characterize genetically intact and defective proviral genomes. Intact open reading frames (ORFs) were further inferred using the CFEIntact tool.ResultsCompared with IRs, INRs had a higher total proviral genome per 106 PBMCs, although the difference did not reach statistically significance. INRs also displayed a significantly higher level of intact proviral genomes per 106 PBMCs and a trend toward a higher proportion of intact sequences. Defective proviruses remained the predominant component of the reservoir in both groups and were broadly comparable in number and composition. In both cohorts, proviral defects were more frequently observed in the 3′ half of the genome.DiscussionOur study reveals a distinct proviral landscape in ART-treated INRs, characterized by elevated levels of intact proviral genomes. These observations suggest that the intact component of the reservoir may represent a clinically relevant feature of incomplete immune reconstitution, and provide a rationale for further studies of reservoir-directed interventions in this population.

The existing predictive models for talaromycosis in people living with HIV without skin lesions are limited by established risk factors and traditional statistical approaches. This study aims to develop an interpretable machine learning(ML) model for predicting the presence of talaromycosis in HIV patients without skin lesions and to validate its clinical applicability. This retrospective multicenter study involved the analysis of electronic medical records from four tertiary hospitals in China, covering the period from 2010 to 2019. The training dataset comprised 1009 HIV patients with opportunistic infections, while external validation was conducted using data from 305 patients at an independent center. From an initial set of 36 variables, twelve key features were selected, including albumin, absolute lymphocyte count, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, C-reactive protein, white blood cell count, platelet count, peripheral or abdominal lymphadenopathy, CD4+ T-cell count, and age. Five ML algorithms were evaluated using tenfold cross-validation. Model performance was measured using the AUC, ACC, and F1-score. Calibration curves and decision curve analysis (DCA) were employed to assess the model’s reliability and clinical net benefit. The optimal model was subsequently implemented as a web-based tool. The Support Vector Machine (SVM) exhibited superior performance compared to other models, achieving an AUC of 0.809 (95

Introduction: The existing predictive models for talaromycosis in HIV-infected patients without skin lesions are limited by established risk factors and traditional statistical approaches. This study aims to develop an interpretable machine learning (ML) model for predicting the risk of talaromycosis in HIV patients without skin lesions and to validate its clinical applicability. Methods This retrospective multicenter study involved the analysis of electronic medical records (EMR) from four tertiary hospitals in China, covering the period from 2010 to 2019. The training dataset comprised 1,009 HIV patients with opportunistic infections, while external validation was conducted using data from 305 patients at an independent center. From an initial set of 36 variables, twelve key features were selected, including albumin, absolute lymphocyte count, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT ratio, C-reactive protein, white blood cell count, platelet count, peripheral or abdominal lymphadenopathy, CD4 + T-cell count, and age. Five ML algorithms were evaluated using 10-fold cross-validation. Model performance was measured using the AUC, ACC, and F1-score. Calibration curves and decision curve analysis (DCA) were employed to assess the model's reliability and clinical net benefit. The optimal model was subsequently implemented as a web-based tool. Results The Support Vector Machine (SVM) exhibited superior performance compared to other models, achieving an AUC of 0.809 (95% CI: 0.778–0.838), an ACC of 0.714, and an F1-score of 0.689. External validation demonstrated enhanced performance metrics, with an AUC of 0.921 (95% CI: 0.889–0.951), ACC of 0.853, and an F1-score of 0.819. DCA indicated a significant net clinical benefit across various risk thresholds, and calibration curves showed strong concordance between predicted and observed risks. Conclusion This interpretable SVM model effectively stratifies the risk of talaromycosis in HIV patients in endemic regions, aligning with WHO recommendations for targeted prophylaxis. Its integration into a web-based tool enhances clinical accessibility for early intervention in resource-constrained settings. Ongoing prospective trials (ChiCTR1900021195) are anticipated to further substantiate its real-world impact.

The eradication of HIV remains challenging, primarily due to the persistence of latent HIV reservoirs within the human body that evade immune detection, even in the context of effective antiretroviral therapy (ART). These reservoirs, principally comprising CD4+ T-cells, are characterised by their heterogeneity and dynamic nature, rendering their identification and targeted elimination ineffectual. This review examines recent advances in the identification of cell surface markers associated with HIV latency, emphasising their potential utility in the detection of HIV reservoir cells. Thus, markers such as CD2, CD20, CD30, CD32a, CD69, CD73, CD98, CD127, CD161, and VLA-4, amongst others, are presented herein and evaluated based on their roles in HIV infection dynamics, latency maintenance, and reactivation potential. While promising candidates such as CD32a and PD-1 demonstrate significant enrichment of HIV DNA and replication-competent provirus, observations remain inconsistent across studies, highlighting the need for further research. Additionally, this review introduces P-selectin glycoprotein ligand-1 (PSGL-1), a cell surface molecule extensively studied in relation to its role in inflammation, as a potential marker for HIV reservoir cells. By consolidating current evidence, this article revisits the intriguing realm of HIV reservoir cells and provides knowledge and a broader canvas for their identification via detection of specific cell surface molecules.

Background::Toxoplasmic encephalitis (TE) is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome (AIDS). However, the optimal timing of antiretroviral therapy (ART) initiation in these patients remains controversial. This study aims to investigate the differences in outcomes of ART initiation at different times, in order to help clarify the treatment timing of AIDS-associated TE.Methods::This multicenter prospective observational study included 87 patients recruited from 11 research centers in China (from March 2019 to December 2022). Of the patients, 38 were assigned to the early ART group (initiating ART within 2 weeks after anti- Toxoplasma treatment initiation), and the remaining 49 patients received deferred ART (initiating ART at least 2 weeks after anti- Toxoplasma treatment initiation). The main outcomes included mortality and emergence of immune reconstitution inflammatory syndrome (IRIS). Human immunodeficiency virus (HIV)-1 viral load and CD4 + T-cell counts at weeks 24 and 48 were observed. Results::The number of deaths (1 vs. 5, P = 0.225) and incidence of IRIS (2.6% vs. 0, P = 0.437) were not significantly different between the early and deferred ART groups at week 48. Early ART initiation did not contribute significantly to HIV-1 viral load control (<50 copies/mL, n = 8 vs. n = 3 at week 24, P = 0.142; n = 7 vs. n = 7 at week 48, P = 1.000). The median CD4 + T-cell counts between the two groups were not significantly different, either at week 24 (155 vs. 91 cells/mm 3, P = 0.837) or at week 48 (181 vs. 146 cells/mm 3, P = 0.219). Conclusion::In patients with AIDS-associated TE, early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality, IRIS, and HIV virological and immunological outcomes.Trial registration::This study was registered (registration number: ChiCTR1900021195) as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry (chictr.gov) on February 1, 2019. Enrollment for this study began in March 2019.

BackgroundImmunological non-responders (INRs) among people living with HIV have inherently higher mortality and morbidity rates. The underlying immunological mechanisms whereby failure of immune reconstitution occurs in INRs require elucidation.MethodHIV DNA and HIV cell-associated RNA (CA-HIV RNA) quantifications were conducted via RT-qPCR. Transcriptome sequencing (RNA-seq), bioinformatics, and biological verifications were performed to discern the crosstalk between host and viral factors. Flow cytometry was employed to analyze cellular activation, proliferation, and death.ResultsHIV DNA and CA-HIV RNA levels were observed to be significantly higher in INRs compared to immunological responders (IRs). Evaluation of CD4/CD8 ratios showed a significantly negative correlation with HIV-1 DNA in IRs, but not in INRs. Bioinformatics analyses and biological verifications showed IRF7/INF-α regulated antiviral response was intensified in INRs. PBMCs of INRs expressed significantly more HIV integrase-mRNA (p31) than IRs. Resting (CD4+CD69- T-cells) and activated (CD4+CD69+ T-cells) HIV-1 reservoir harboring cells were significantly higher in INRs, with the co-occurrence of significantly higher cellular proliferation and death in CD4+ T-cells of INRs.ConclusionIn INRs, the systematic crosstalk between the HIV-1 reservoir and host cells tends to maintain a persistent antiviral response-associated inflammatory environment, which drives aberrant cellular activation, proliferation, and death of CD4+ T-cells.

Our study aimed to develop and validate a nomogram to assess talaromycosis risk in hospitalized HIV-positive patients. Prediction models were built using data from a multicentre retrospective cohort study in China. On the basis of the inclusion and exclusion criteria, we collected data from 1564 hospitalized HIV-positive patients in four hospitals from 2010 to 2019. Inpatients were randomly assigned to the training or validation group at a 7:3 ratio. To identify the potential risk factors for talaromycosis in HIV-infected patients, univariate and multivariate logistic regression analyses were conducted. Through multivariate logistic regression, we determined ten variables that were independent risk factors for talaromycosis in HIV-infected individuals. A nomogram was developed following the findings of the multivariate logistic regression analysis. For user convenience, a web-based nomogram calculator was also created. The nomogram demonstrated excellent discrimination in both the training and validation groups [area under the ROC curve (AUC) = 0.883 vs. 0.889] and good calibration. The results of the clinical impact curve (CIC) analysis and decision curve analysis (DCA) confirmed the clinical utility of the model. Clinicians will benefit from this simple, practical, and quantitative strategy to predict talaromycosis risk in HIV-infected patients and can implement appropriate interventions accordingly.

Human immunodeficiency virus (HIV) infection has evolved into an established global pandemic over the past four decades; however, despite massive research investment globally, the precise underlying mechanisms which are fundamental to HIV-related pathogenesis remain unclear. Single cell ribonucleic acid (RNA) sequencing methods are increasingly being used for the identification of specific cell-type transcriptional changes in HIV infection. In this scoping review, we have considered information extracted from fourteen published HIV-associated single-cell RNA sequencing-related studies, hoping to throw light on the underlying mechanisms of HIV infection and pathogenesis, and to explore potential candidate biomarkers for HIV disease progression and antiviral treatment. Generally, HIV positive individuals tend to manifest disturbances of frequency of multiple cellular types, and specifically exhibit diminished levels of CD4+ T-cells and enriched numbers of CD8+ T-cells. Cell-specific transcriptional changes tend to be linked to cell permissiveness, hyperacute or acute HIV infection, viremia, and cell productivity. The transcriptomes of CD4+ T-cell and CD8+ T-cell subpopulations are also observed to change in HIV-positive diabetic individuals, spontaneous HIV controllers, individuals with high levels of HIV viremia, and those in an acute phase of HIV infection. The transcriptional changes seen in B cells, natural killer (NK) cells, and myeloid dendritic cells (mDCs) of HIV-infected individuals demonstrate that the humoral immune response, antiviral response, and immune response regulation, respectively, are all altered following HIV infection. Antiretroviral therapy (ART) plays a crucial role in achieving immune reconstitution, in improving immunological disruption, and in mitigating immune system imbalances in HIV-infected individuals, while not fully restoring inherent cellular transcription to levels seen in HIV-negative individuals. The preceding observations not only illustrate compelling advances in the understanding of HIV-associated immunopathogenesis, but also identify specific cell-type transcriptional changes that may serve as potential biomarkers for HIV disease monitoring and therapeutic targeting.

PURPOSE:Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. METHOD:We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. RESULTS:As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. CONCLUSION:In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

BackgroundIt has been previously demonstrated that intestinal barrier damage is one of the underlying mechanisms leading to frailty in non-HIV-infected aging populations. However, there is a paucity of direct evidence which demonstrates the association between intestinal barrier damage and frailty in people living with HIV (PLWH).MethodsThe present study is a retrospective case control study. Participants older than 50 years old were stratified into a frail/pre-frail group (case group) and non-frail group (control group) according to the Fried frailty phenotype. We collected and curated data concerning socio-demographic variables, psychological states and social functioning, and clinical information associated with the identification of biomarkers of intestinal barrier damage, microbial translocation, and levels of inflammatory cytokines of participants.ResultsThe case group had significantly higher levels of Reg-3α (p=0.042) and I-FABP (p=0.045) compared to the control group. We further observed, after adjusting for confounding factors by logistic regression analysis, that I-FABP levels remained significantly higher in the case group compared to the control group (p=0.033). Also, Fried Phenotype scores positively correlated with I-FABP levels (rs=0.21, p=0.01), LPS levels (rs=0.20, p=0.02), and sCD14 levels (rs=0.18, p=0.04). Moreover, the study confirmed both the positive correlation between inflammatory cytokines (IL-6 and IP-10) with frailty in aging PLWH, and between inflammatory cytokines (IL-6, IL-8 and IP-10) with biomarkers of intestinal barrier dysfunction in older PLWH.ConclusionThe present study indicates that the inflammation induced by intestinal barrier damage/dysfunction is likely to contribute to frailty in aging PLWH.

Abstract Background Recent evidence indicates that frailty is prevalent in PLWH compared to those without HIV, especially in the elderly population. However, the underlying mechanisms fundamental to this phenomenon reman unclear. Gut damage and increased microbial translocation are hallmarks of HIV infection, and are known to promote and perpetuate the chronic systemic inflammation seen in PLWTH. Meanwhile, it has been observed that chronic inflammation also contributes to the frailty. Herein, we investigate the association between frailty and intestinal barrier dysfunction in PLWH. Methods This cross-sectional study was designed to assimilate and analyze clinical data and results of blood samples in PLWH. According to frailty phenotype assessment, participants were stratified into three groups comprising a frailty, a pre-frailty, and a non-frailty group. We subsequently measured the levels of biomarkers of gut damage, microbial translocation, and levels of inflammatory cytokines to assess the relationship between these biomarkers and frailty. Results One hundred and fifty one PLWH over 50 years of age were involved in this study, and were stratified into three groups: 73 patients in the non-frailty group, 61 patients in the pre-frailty group, and 17 patients in the frailty group. Their incidence of anxiety, depression, and stress was calculated to be higher in the frailty group than other two groups (p< 0.05). The concentration of gut damage biomarkers in serum, i.e., levels of regenerating islet-derived protein-3α (REG-3α) and intestinal fatty acid-binding protein (I-FABP), showed significant positive correlations with frailty, and was observed to be highest in the frailty group. On the contrary, no significant association was observed between the hematological biomarkers of microbial translocation with frailty. Additionally, IL-6, IP-10, and TNF-α concentrations in plasma were found to positively correlate with frailty in aging PLWH (i.e., these biomarkers had the highest concentrations in the frailty group). Conclusion Our study revealed that the inflammation induced by gut damage may contribute to frailty in elder PLWH. Disclosures All Authors: No reported disclosures

Objective To compare the clinical features of AIDS patients complicated with moderate to severe Pneumocystis pneumonia（AIDS/PCP） with versus without cytomegalovirus（CMV） viremia to analyze whether CMV viremia has any impact on prognosis of AIDS/PCP patients, and investigate the potential risk factors for mortality of AIDS/PCP patients. Methods Clinical data were collected from 284 AIDS/PCP patients who were treated in the Division of Infectious Diseases, Chongqing Public Health Medical Center from January 2019 to December 2020. The demographic, clinical, laboratory data, and prognosis were compared between the patients who were negative for CMV DNA and those who were positive for CMV DNA. Cox regression model was used to analyze the risk factors for death within one year. Results The prevalence of CMV viremia was 39.4% in the AIDS/PCP population. Compared with CMV DNA-negative patients, the patients with CMV viremia had higher platelet count（P = 0.009） and lactate dehydrogenase（LDH） level（P = 0.035）, lower CD4 + T-lymphocytes count（P = 0.001）, and CD4/CD8 ratio（P = 0.041）, and higher all-cause 1-year mortality. Increased white blood cell count [Exp（B）=1.113,95% CI: 1.015-1.265, P = 0.026], elevated LDH level [Exp（B）=1.002, 95% CI: 1.001-1.003, P ＜ 0.001], pulmonary co-infection [Exp（B）=14.643, 95% CI: 1.982-108.167, P = 0.009] and CMV DNA positive [Exp（B）=1.985, 95% CI: 1.018-3.869, P = 0.044] were independent risk factors for 1-year mortality of AIDS/PCP patients, while antiretroviral therapy（ART） regimens containing integrase strand transfer inhibitors（INSTIs） [Exp（B）=0.076, 95% CI: 0.018-0.319, P ＜ 0.001] was an independent protective factor. Conclusions The laboratory test results and prognosis of AIDS/PCP patients varied with the result of CMV DNA（negative or positive）. Higher white blood cell count and LDH level, ART regimen not containing INSTIs, pulmonary co-infection, and presence of CMV viremia confer a higher risk of mortality. Early targeted treatment can reduce the risk of death and prolong the survival time.

To the Editor : Previous studies have demonstrated the efficacy of bictegravir (B), emtricitabine (F), and teno-fovir alafenamide (TAF) in achieving virological suppression in human immunodeficiency virus (HIV)-infected patients. Virological suppression can be influenced by various factors, with baseline HIV-1 RNA being a critical consideration. Guidelines often use a baseline HIV RNA level of > 500,000 copies/mL as the primary reference indicator for drug selection. [1] However, previous studies on the effectiveness of B/F/TAF have not specifically analyzed patients with baseline HIV RNA > 500,000 copies/mL. In Chongqing, China, where the prevalence of advanced HIV among hospitalized patients living with HIV exceeds 70%, [2] up to 25% of patients have baseline HIV-1 RNA > 500,000 copies/mL in our study, and many patients have opportunistic infections. In such a complex medical setting, the virological suppression rates of patients using B/F/TAF remain uncertain. Therefore, we conducted this real-world retrospective study to gain a more comprehensive understanding of the efficacy and safety of B/F/TAF. The study received approval from the Institutional Review Board of Chongqing Public Health Medical Center (CPHMC) (No. 2023-020-02-KY). Since this study was retrospective and all patient data were analyzed anonymously, the institutional review board waived the requirement for written informed consent. Data were collected from all treatment-naïve HIV

Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.

P-selectin glycoprotein ligand 1（PSGL-1） is a transmembrane glycoprotein that exists on the surface of T lymphocytes and other cells and has a variety of biological activities. PSGL-1 is involved in not only the formation and development of inflammation but also the growth and metastasis of tumor cells. In recent years, PSGL-1 has been found to have an inhibitory effect on HIV infection, acting as a restriction factor for HIV replication. Studies also indicate that PSGL-1 could be a potential new target for HIV treatment in the future. In this article, we aimed to review the biological roles and cellular expression of PSGL-1, as well as PSGL-1’s inhibitory effects on HIV infection and associated mechanisms.

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)-naive 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 & PLUSMN; 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%), gamma-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. Copyright (c) 2023 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/).