ObjectiveThe role of natural killer (NK) cells, which mediate innate immunity, in the immune reconstitution of people living with HIV (PLWH) remains unclear. Our previous research indicated that early activation of CD56dimCD16dim/- NK cells plays an important role in the recovery of CD4+ T cells in immunological non-responders (INRs) after ART. This study mainly focuses on the profiles of cell receptors and their relative ligands for NK cells and CD4+ T cells exhibited on INRs and immunological responders (IRs) in order to analyze the impact of differential immune status on immune reconstitution in PLWH receiving ART.MethodsThis study included 66 PLWH who had been on ART for 4 years, comprising 32 INRs and 34 IRs. Using flow cytometry, we examined the expression of cell receptors and ligands for NK cells and CD4+ T cells in PBMCs, as well as the differentiation of CD4+ T cells.ResultsThe expression of NKG2D ligands, including MICA/B and ULBP2-5, on CD4+ T cells in INRs is elevated prior to ART. Further research found that the expression of CD95 on MICA/B+CD4+ T cells and ULBP2-5+CD4+ T cells was higher in INRs before ART compared to IRs. Simultaneously, the percentages of death receptor CD95 expression on MICA/B+CD4+ T cells and on ULBP2-5+CD4+ T cells before ART were negatively correlated with CD4+ T-cell counts and ΔCD4. Among the CD4+ T-cell subsets, an imbalance persists in the CD4+ Tcm and CD4+ Temra subsets in both INRs and IRs, before or after ART. CD4+ T cells exhibit elevated levels of activation, proliferation, exhaustion, and apoptosis prior to ART initiation. However, CD4+ T-cell activation and proliferation normalize post-ART, while apoptosis and exhaustion levels remain significantly elevated. Regardless of ART, the anti-apoptotic capacity of CD4+ T cells in INRs is still lower than that of IRs and healthy controls (HCs). Before ART, the frequency of CD31 expression on naive CD4+ T cells in INRs is lower than that in IRs and HCs. Following ART, the amounts of CD31+ Tn from CD4+ T cells remain impaired in both INRs and IRs compared to HCs.ConclusionThe upregulation of related ligands for the NKG2D receptor on CD4+ T cells in INRs is associated with increased susceptibility of CD4+ T cells to NK cell-mediated killing. CD95 may plays an important role in poor recovery of CD4+ T cells co-expressing NKG2D-related ligands. The imbalance in CD4+ Tcm and CD4+ Temra subset homeostasis and impaired CD31 expression on naive CD4+ T cells in INRs are associated with poor immune reconstitution outcomes.

Antiretroviral therapy has extended the life expectancy of people with HIV (PWH), leading to a rapidly expanding ageing population of PWH worldwide, including in low- and middle-income countries. The interaction between ageing and chronic HIV infection is closely associated with immunosenescence, and PWH are widely regarded as a model of accelerated immune ageing. Immunosenescence, characterized by a progressive decline in immune function and increased susceptibility to infections, contributes to a higher burden of age-related comorbidities and cancers, posing a major long-term health challenge for this population. Main body. The main focus of this review is on immunosenescence-related phenotypic and functional alterations in innate immune cells in PWH, including natural killer cells, monocytes, macrophages, and dendritic cells. It also outlines immunosenescence-related changes in T and B cells in the context of ageing and chronic HIV infection, such as thymic atrophy, loss of naïve T cell diversity, expansion of terminally differentiated and exhausted T-cell subsets, the impact of cytomegalovirus co-infection, and the emergence of age-associated B cells that impair humoral immunity and vaccine responsiveness. Furthermore, it discusses how persistent low-grade inflammation, mitochondrial damage induced by viral proteins and certain antiretroviral regimens, together with lifestyle factors such as cigarette smoking, accelerate systemic immune ageing, and summarizes emerging therapeutic and lifestyle strategies aimed at mitigating immunosenescence and improving long-term immune health, while noting that robust evidence remains limited. Despite growing insights into HIV-associated immune ageing, there is still no universally applicable biomarker of immunosenescence. This gap underscores the need to develop robust, population-tailored biomarker panels and targeted interventions for PWH, to support integrated strategies that combine antiretroviral therapy with immune restoration and anti-ageing approaches, ultimately improving immune health and quality of life.

Type I interferons (IFNs), particularly IFN-α, occupy a central paradox in HIV-1 infection: they provide an essential early antiviral barrier that limits initial dissemination, yet their sustained activation contributes to chronic immune activation, CD4+ T-cell dysfunction, and incomplete viral control. This duality—protective in acute infection but pathogenic during chronic disease—remains a major unresolved challenge for interferon-based therapeutic strategies in HIV-1. Recent advances in ISG functional profiling, IFN-α subtype–specific antiviral potency, and the development of targeted innate-pathway modulators (e.g., STING-selective agonists, ncRNA regulators, TLR7 activators) have renewed interest in reevaluating interferon-centered approaches. These developments make it timely to reassess whether IFN-α can be safely and effectively integrated into modern HIV-1 therapeutic concepts, particularly in early-infection windows or in rationally designed combination regimens. In this review, we synthesize current knowledge of interferon-mediated restriction mechanisms, the hierarchy of key antiviral ISGs (e.g., APOBEC3G, MX2, BST2), and HIV-1 evasion of the JAK–STAT and cGAS–STING pathways. We further analyze how dose, timing, and IFN-α subtype contribute to divergent antiviral versus inflammatory outcomes across different stages of infection. Emerging precision strategies that modulate interferon signaling without triggering systemic inflammation offer promising translational directions. Balancing antiviral efficacy with immune homeostasis will be essential for developing next-generation interferon-based interventions aimed at durable control or functional cure of HIV-1 infection.

The long-term effects of combined antiretroviral therapy (ART) on liver fibrosis patterns in adults living with human immunodeficiency virus (HIV) and chronic hepatitis B virus (HBV) are not well understood. Therefore, this study aimed to investigate the trajectories of liver fibrosis and identify the associations of baseline variables with different patterns of liver fibrosis evolution. A total of 333 individuals with HIV/HBV co-infection and undergoing long-term ART were enrolled in this study. Demographic, clinical, and biochemical data were collected at baseline and during annual visits. Group-based trajectory models (GBTMs) were used to detect the patterns of liver fibrosis evolution based on longitudinal data of fibrosis-4 (Fib-4) and aspartate aminotransferase to platelet ratio index (APRI) scores. Logistic regression analysis was performed to identify baseline predictors of liver fibrosis evolution. The median age of all participants was 33 years. Among them, 89.5% initially received TDF-containing ART. GBTMs identified two distinct patterns of liver fibrosis evolution using either APRI or Fib-4 scores. The majority of individuals (78.5% for APRI and 75.3% for Fib-4; pattern A) showed stable or low fibrosis with no progression, while the remaining participants showed regression from high fibrosis levels (21.5% for APRI and 24.7% for Fib-4; pattern B). Pattern A participants were younger and had higher CD4+ cell counts, higher lymphocyte cell counts, higher white blood cell counts, and lower platelet counts at baseline compared to pattern B participants. For HIV/HBV co-infected patients with varying degrees of initial liver fibrosis, long-term ART has shown distinct patterns of alleviating liver fibrosis.

Human immunodeficiency Virus (HIV) and Mycobacterium tuberculosis (Mtb) co-infection presents a significant public health challenge worldwide. Comprehensive assessment of the immune response in HIV/Mtb co-infection is complex and challenging. CD8+T cells play a pivotal role in the adaptive immune response to both HIV and Mtb. The differentiation of CD8+T cells follow a hierarchical pattern, with varying degrees of exhaustion throughout the process. Memory stem T cells (TSCM cells) is at the apex of the memory T lymphocyte system, which has recently emerged as a promising target in immunotherapy. In this context, we discuss the alterations of CD8+TSCM cells in HIV/Mtb mono- and co-infection, their implications and clinical significance, and potential for improving immunotherapy.

Introduction:A novel recombinant antigen-based capture enzyme immunoassay (RAg-CEIA) was optimized and used to determine technical parameters for estimating human immunodeficiency virus type 1 (HIV-1) incidence in China. Methods:We employed orthogonal experimental design to optimize RAg-CEIA by adjusting raw material dilution ratios. The assay was used to measure normalized optical density (ODn) values in 171 longitudinal plasma specimens from 51 HIV-1 seroconverting individuals, plotted against estimated days post-seroconversion. We determined the optimal ODn threshold value for differentiating recent from long-term infections and calculated the mean duration of recent infection (MDRI) for incidence estimation. The false recent rate (FRR) was determined using 481 HIV-1 antibody-positive specimens with infection durations exceeding twice the MDRI. Results:Optimal RAg-CEIA parameters were established with a raw material dilution ratio of 1/12 for calibrator preparation and an enzyme conjugate titer of 1:1200. ODn values demonstrated consistent temporal increases across HIV-1 seroconverting individuals, though with notable kinetic heterogeneity in individual responses. The optimal ODn threshold value of 0.8 for distinguishing recent from long-term infections corresponded to an MDRI of 205 days and an FRR of 4.78%. Conclusions:The optimized RAg-CEIA effectively differentiates recent from long-term HIV-1 infections at the population level, enabling reliable HIV-1 incidence estimation in China.

This study compared the immunogenicity of inactivated SARS-CoV-2 vaccines between people living with HIV (PLWH) and HIV-negative individuals. We recruited 120 PLWH and 53 HIV-negative individuals aged 18–59 years who had received an inactivated SARS-CoV-2 vaccine in two Chinese cities between April and June 2021. Blood samples were tested for immunogenicity of the inactivated SARS-CoV-2 vaccines. The prevalence and severity of adverse events associated with SARS-CoV-2 vaccines were similar between PLWH and HIV-negative individuals. The seropositivity of neutralizing activity against authentic SARS-CoV-2, of the total amount of antibody (total antibody) and of S-IgG were 71.3%, 81.9%, and 92.6%, respectively, among fully vaccinated PLWH. Among all participants, PLWH had lower neutralizing activity, total antibody, S-IgG, and T-cell-specific immune response levels, compared to HIV-negative individuals, after controlling for types of vaccine, time interval between first and second dose, time after receiving the second dose, and sociodemographic factors. PLWH with a longer interval since HIV diagnosis, who received their second dose 15–28 days prior to study commencement, and who had an interval of ≥21 days between first and second dose had higher neutralizing activity levels. The immunogenicity of the inactivated SARS-CoV-2 vaccines was lower among PLWH as compared to HIV-negative individuals. Vaccination guideline specific for PLWH should be developed.

Abstract. Antiretroviral therapy against human immunodeficiency virus (HIV) is effective in controlling viral replication but cannot completely eliminate HIV due to the persistence of the HIV reservoir. Innate and adaptive immune responses have been proposed to contribute to preventing HIV acquisition, controlling HIV replication and eliminating HIV-infected cells. However, the immune responses naturally induced in HIV-infected individuals rarely eradicate HIV infection, which may be caused by immune escape, an inadequate magnitude and breadth of immune responses, and immune exhaustion. Optimizing these immune responses may solve the problems of epitope escape and insufficient sustained memory responses. Moreover, immune interventions aimed at improving host immune response can reduce HIV reservoirs, which have become one focus in the development of innovative strategies to eliminate HIV reservoirs. In this review, we focus on the immune response against HIV and how antiviral immune responses affect HIV reservoirs. We also discuss the development of innovative strategies aiming to eliminate HIV reservoirs and promoting functional cure of HIV infection.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic has tested the ability of universities to provide a high-quality, safe educational experience for students due to campuses shutting down. As a result, online learning could shift from a traditional classroom teaching mode and make education accessible to students. Previous studies have used individual online teaching cases to exploit a variety of online learning tools to ensure the continuation of medical education during this difficult time in China. However, for the first time, we have conducted a systematic review of local online teaching approaches, existing challenges, and potential solutions. Purpose: We present the issues and experience of conducting online medical teaching practices in China with the aim of communicating them to our peers in other countries or regions when examining the transition to e-learning during the COVID-19 pandemic and beyond. Methods: We searched the keywords below from public databases and reviewed relevant publications reporting on medical online teaching in China during the COVID-19 pandemic to analyze and summarize the online tools, modalities, and challenges. Results: We listed common online teaching tools and described a variety of online teaching modalities, as well as possible challenges. We also discussed potential solutions for those challenges, as well as the impact of the transition to online teaching on traditional education. Conclusion: By investigating local online medical teaching in China, we present useful tools and modalities that have been successfully exploited in education during the difficult time of COVID-19, although some challenges remain. The exploration of the transition to online teaching or learning will likely continue to have a profound impact on traditional classroom teaching.

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.

>Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has caused the global outbreak of coronavirus disease 2019(COVID-19). By far, more than 35 million people had been infected by SARS-CoV-2, resulting in more than 1 million deaths globally. It is well recognized that SARSCoV-2 preferentially attacks pulmonary epithelial cells,leading to acute respiratory distress syndrome(ARDS).Remarkably,

Background: Hepatitis B virus (HBV) coinfection is common in HIV-positive patients. HIV infection modifies the natural course of HBV infection, leading to a faster progression of liver-related morbidity and mortality than is observed in HBV mono-infected patients. This systematic review and meta-analysis evaluates the current clinical evidence regarding the use of oral tenofovir disproxil fumarate (TDF)-based treatments in patients coinfected with HIV and HBV. Methods: We performed a comprehensive literature search in PubMed and Web of Science. Supplementary searches were conducted in Google Scholar and Clinicaltrials. gov. We conducted a random effects meta-analysis using the event rate (ER) to estimate the incidence of HBV seroconversion. A subgroup meta-analysis was performed to assess the moderate effects of demographic and disease-related variables on HBsAg loss. This review is registered in the PROSPERO database (CRD42018092379). Results: We included 11 studies in the review. The immunological effects of oral TDF-based Pre-exposure prophylaxis (PrEP) treatment in patients with HIV-HBV coinfection were 0.249 for HBeAg loss, 0.237 for HBeAg conversion, 0.073 for HBsAg loss, and 0.055 for HBsAg conversion. The factors associated with HBsAg loss were the baseline HBV viral load, participant's location, and a history of exposure to lamivudine/emtricitabine (3TC/FTC) (all p < 0.05). A trend toward a negative relationship between the baseline CD4+ T-cell count and HBsAg loss was observed (p = 0.078). Conclusion: This systematic review and meta-analysis demonstrated that TDF-containing regimens are effective at stimulating HBeAg loss (24.9%), HBeAg conversion (23.7%), HBsAg loss (7.3%), and HBsAg conversion (5.5%) in HIV-HBV coinfected patients. The moderator analysis showed that HBV viral load, the location of participants, and prior exposure to 3TC/FTC are factors associated with HBsAg loss. Asian ethnicity, prior exposure to 3TC, and a nondetectable baseline HBV viral load are associated with lower odds of HBsAg loss. Well-designed prospective cohort studies and randomized controlled trials (RCTs) with large sample sizes are required for the investigation of potential predictors and biological markers associated with strategies for achieving HBV remission in patients with HIV-HBV coinfection, which is a matter of considerable importance to clinicians and those responsible for health policies.