Antibody imprinting is well recognized, yet its long-term dynamics and epitope specificity remain poorly understood. Here, we studied individuals sequentially infected with SARS-CoV-1 (SARS-1) and SARS-CoV-2 (SARS-2) over two decades and found durable imprinting of antibody responses following SARS-2 BF.7 breakthrough infection. Approximately 60% of isolated monoclonal antibodies were SARS-1 imprinted and targeted conserved receptor-binding domain regions, whereas 37% overcame imprinting to recognize the SARS-2 receptor-binding motif overlapping the ACE2-binding site. Notably, some SARS-1-only antibodies retained germline-like features and neutralizing activity 20 years after infection. One exceptionally imprinted broadly neutralizing antibody, THZ937, protected hamsters against contact and airborne transmission of Omicron EG.5.1, demonstrating the functional relevance of durable imprinted antibodies. Together, these findings define the remarkable longevity and molecular basis of antibody imprinting and provide insights for pan-sarbecovirus vaccine design.

Antiretroviral therapy (ART) has significantly extended the life expectancy of people with HIV (PWH), rendering population ageing and immunosenescence prominent clinical priorities. T-cell senescence is linked to mitochondrial dysfunction and drives age-related immune remodelling, yet how HIV infection and ageing jointly shape CD4+ and CD8+ T-cell immunophenotypes and mitochondrial remodelling remains unclear. This cross-sectional study included 61 PWH on suppressive ART for ≥ 12 months and 61 age- and sex-matched HIV-negative men who have sex with men, stratified into younger (≤ 35 years) and older (≥ 50 years) groups. Multiparameter flow cytometry was used to profile CD4+ and CD8+ T-cell differentiation, stemness, activation/exhaustion, and metabolic phenotypes, together with mitochondrial mass and membrane potential. We found that ageing and HIV infection were associated with T-cell remodelling, characterized by expanded late-differentiated phenotypes and reduced stem-like, homeostatic and costimulatory CD4+ and CD8+ T-cell subsets, as indicated by upregulated CD57 and CX3CR1 and downregulated CD45RA+CD31+, FOXO1, and CD28. Notably, younger PWH had an ageing-like CD4+ T-cell profile, with higher CD57, CX3CR1 and TIGIT expression than younger HIV-negative individuals. In contrast, HIV-related CD8+ T-cell perturbations (KLRG1, CXCR3, NKG2C and CD95) were more pronounced in older PWH. PWH exhibited increased mitochondrial mass and membrane potential in both total and senescent-like CD4+ and CD8+ T cells, particularly in CD8+ T cells from older PWH. In CD4+ T cells, KLRG1 and CX3CR1 expression correlated positively with age, and inversely with CD4+ T-cell counts and CD4/CD8 ratio. By contrast, FOXO1 expression in CD8+ T cells was inversely associated with age, late-differentiation markers, and ART duration in PWH. Overall, age is a major driver of T-cell immunosenescence, and HIV infection modulates and exacerbates these alterations. Mitochondrial stress, FOXO1 downregulation and immune network remodelling support a multifaceted model of HIV-associated immune ageing that may contribute to heterogeneous immune reconstitution in PWH, highlighting potential targets to mitigate immune ageing.

BackgroundOral health is increasingly recognized as a crucial determinant of overall health in people living with HIV/AIDS (PLWHA). Specifically, the oral mycobiome may play a pivotal role in HIV-associated oral complications. However, the fungal species involved and their potential as biomarkers for HIV-related oral conditions remain poorly understood. This study investigates salivary fungal profiles in PLWHA who have sex with men (MSM), focusing on diversity, functional shifts, and correlations with disease progression.MethodsA cross-sectional study included 25 MSM participants divided into five groups: HIV-negative controls (n = 5) and four HIV-positive groups stratified by CD4 count: Stage 0 (HIV RNA-positive/antibody-negative; n = 5), Stage 1 (CD4 ≥500 cells/μL; n = 5), Stage 2 (CD4 200–499 cells/μL; n = 5), and Stage 3 (CD4 <200 cells/μL or opportunistic infections; n = 5). Saliva samples were collected and analyzed using metagenomic sequencing (Illumina NovaSeq platform). Bioinformatic analyses included genome assembly (MEGAHIT), gene clustering (CD-HIT), gene abundance calculation (SOAPaligner), species annotation (BLASTP), and KEGG pathway annotation (KOBAS 2.0). Statistical analyses (Kruskal-Wallis tests, Spearman’s correlation) assessed associations between fungal profiles, CD4 count, and viral loads.ResultsA total of 51 fungal genera were identified, with Pseudogymnoascus being the most abundant. Functional analysis revealed 113 shared KEGG pathways, of which 69 were unique to Stage 3, primarily related to metabolic and disease-related processes. Notably, Auricularia exhibited a positive correlation with CD4 count (P ≤ 0.01), while Mucor showed a negative correlation (P = 0.0299).ConclusionsSalivary mycobiome composition and function shift significantly across HIV stages, reflecting immune decline. Pseudogymnoascus dominance challenges conventional views of oral fungal ecology in immunocompromised hosts. These findings highlight the mycobiome’s diagnostic potential for monitoring HIV-related oral health. Longitudinal studies are needed to validate clinical relevance.

Abstract Background Ainuovirine (ANV) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infection. This study aimed to evaluate the safety, pharmacokinetics, and antiviral activity of short-term ANV monotherapy in antiretroviral treatment-naive adults with HIV-1.Table 1.Summary statistics of pharmacokinetic parameters of ainuovirine after single-dose and multi-doses in treatment-naïve HIV-infected adults. Data are expressed in median ± standard deviation (min, max); AUC0–t, area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration; AUC0-t,ss, AUC0-t at steady state; AUC0-∞,ss, AUC from time zero to infinity at steady state; AUC0-τ, AUC at steady state; AUC_%Extrap, percentage of extrapolated AUC; Cmax, maximum plasma concentration; Cmax,ss, Cmax at steady state; Cmin,ss, minimum plasma concentration at steady state; Cav,ss, average steady state concentration; CLss/F, apparent clearance at steady state; DF, degree of fluctuation; MRT0-∞, mean retention time from time zero to infinity; Ra, accumulation ratio; Tmax, time to maximum plasma concentration; Tmax,ss, Tmax at steady state; T1/2z, plasma terminal half-life; Vz/F, apparent volume of distribution; λz, elimination rate constant. Methods A single-center, open-label, dose-ranging study was conducted among 28 treatment-naive adults with HIV-1. Participants received ainuovirine monotherapy, 75, 150, or 300 mg, once daily, for 10 days.Figure 1.Mean change from baseline in HIV RNA.Data are expressed in median±standard deviation. Results Baseline characteristics were similar across dose cohorts (75 mg, n=8; 150 mg, n=10; 300 mg, n=10). Across all dose cohorts, all adverse events were rated as mild to moderate in severity. No serious adverse event was reported. Pharmacokinetic parameters are shown in Table 1. ANV was readily absorbed, with the maximum concentration achieved at a median time of approximately 2-3 h after dosing. The ANV exposure (AUC and Cmax) increased slightly greater than the dose proportionality after single dose (day 1). Plasma ANV concentration reached the steady state at day 10 of dosing. Saturated Cmax,ss, AUCmax,ss, and C24h,ss were observed at 150 and 300 mg on day 10 after repeated dosing. Mean changes in HIV RNA from baseline (log10 copies/mL [90%CI]) were -1.73 [-1.90, -1.57], -1.72 [-1.87, -1.57], and -1.66 [-1.80, -1.51], respectively, on day 11 (Figure 1). Conclusion ANV demonstrated favorable safety and pharmacokinetics, and potent antiviral activity in treatment-naive adults with HIV-1.An once-daily dosing regimen of 150 mg was recommended for subsequent confirmatory efficacy trial. Disclosures Li Zhang, M.S., Jiangsu Aidea Pharmaceutical Co., Ltd.: Honoraria Xinming Yun, PhD, Jiangsu Aidea Pharmaceutical Co., Ltd.: Honoraria Hong Qin, MD, PhD, Jiangsu Aidea Pharmaceutical Co., Ltd: Honoraria

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.

BackgroundEngaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual’s positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect.MethodsBased on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200–499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM.ResultsThe core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts.ConclusionAs HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

Copper-mediated cell death presents distinct pathways from established apoptosis processes, suggesting alternative therapeutic approaches for colon cancer. Our research aims to develop a predictive framework utilizing long-noncoding RNAs (lncRNAs) related to cuproptosis to predict colon cancer outcomes while examining immune interactions and intercellular signaling. We obtained colon cancer-related human mRNA expression profiles and clinical information from the Cancer Genome Atlas repository. To isolate lncRNAs involved in cuproptosis, we applied Cox proportional hazards modeling alongside the least absolute shrinkage and selection operator technique. We elucidated the underlying mechanisms by examining the tumor mutational burden, the extent of immune cell penetration, and intercellular communication dynamics. Based on the model, drugs were predicted and validated with cytological experiments. A 13 lncRNA–cuproptosis-associated risk model was constructed. Two colon cancer cell lines were used to validate the predicted representative mRNAs with high correlation coefficients with copper-induced cell death. Survival enhancement in the low-risk cohort was evidenced by the trends in Kaplan–Meier survival estimates. Analysis of immune cell infiltration suggested that survival was induced by the increased infiltration of naïve CD4+ T cells and a reduction of M2 macrophages within the low-risk faction. Decreased infiltration of naïve B cells, resting NK cells, and M0 macrophages was significantly associated with better overall survival. Combined single-cell analysis suggested that CCL5–ACKR1, CCL2–ACKR1, and CCL5–CCR1 pathways play key roles in mediating intercellular dialogues among immune constituents within the neoplastic microhabitat. We identified three drugs with a high sensitivity in the high-risk group. In summary, this discovery establishes the possibility of using 13 cuproptosis-associated lncRNAs as a risk model to assess the prognosis, unravel the immune mechanisms and cell communication, and improve treatment options, which may provide a new idea for treating colon cancer.

BACKGROUND:Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV. METHODS:Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses. RESULTS:ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). CONCLUSIONS:Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure. TRIAL REGISTRATION:Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Background. Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with human immunodeficiency virus (HIV)-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400 mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among HIV-positive men who have sex with men (MSM). Methods. This multicenter, open-label, randomized clinical trial enrolled MSM aged >= 18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV (400 mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/mL) at 48 weeks per US Food and Drug Administration Snapshot analysis. Results. Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression, and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (P < .001), respectively, discontinued treatment because of adverse effects, death, or lost to follow-up. The median increase of CD4 count was 181 and 223 cells/mu L (P = .020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < .001). Conclusions. BIC/FTC/TAF was more efficacious and safer than EFV (400 mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

BACKGROUND:Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. METHODS:The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 + ) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. RESULTS:The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10 -unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10 -unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. CONCLUSIONS:This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.

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/).

T follicular helper (Tfh) cells and their interactions with B cells within the germinal center play extensive roles in human immunodeficiency virus (HIV) pathology. However, their association with immune reconstitution during antiretroviral therapy (ART) is still unclear. The aim of this study was to determine the impact of Tfh and memory B cell function on T helper cell recovery in patients with acute or chronic HIV infection. A total of 100 HIV-infected individuals were enrolled in our study, classified into acute and chronic HIV infection groups (60 and 40, respectively), and subsequently classified into immunological responder (IR) and immunological nonresponder (INR) subgroups according to immune recovery outcomes after 96 weeks of ART. Liquid chromatography-mass spectrometry was used to quantify the temporal regulation patterns of B and CD4(+) T-cell profiles among patients, and flow cytometry was used to investigate certain subsets of B and T cells. Here we showed that the prevalence of Tfh cells in the T helper cell population correlated negatively with CD4(+) T-cell recovery. The proportion of CXCR3(-) Tfh cells in patients with acute or chronic infection was associated with CD4(+) T-cell count recovery, and the proportion of CD21(+) memory B cells at baseline was significantly higher in those with improved immune recovery outcomes. Universal proteomic dysregulation of B and CD4(+) T cells at baseline was detected in patients with acute infected and poor CD4(+) T-cell recovery. Proteomics analysis revealed distinct temporal regulation profiles of both T helper cells and B cells between IRs and INRs among patients with acute infection. Our results suggest that the functions of memory B cells in INRs are dysregulated at the early stage of ART, possibly through disruption of Tfh cell function. The frequency and function of Tfh cells and their subsets are potential predictors of poor immune recovery.

Background::Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals.Methods::Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated.Results::SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs. Conclusions::SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.

Interactions between T follicular helper (Tfh) cells and germinal center B cells are essential for the differentiation of B cells and specific antibody responses against HIV-1 infection. However, the extent to which HIV-1 infection affects the dynamic interplay between these two cell populations in the bloodstream remains unclear. In this study, the dynamics of circulating Tfh (cTfh) and B cells and their relationship in individuals with acute and chronic HIV-1 infection were investigated. Twenty-five study subjects were enrolled from the Beijing PRIMO clinical cohort, a prospective cohort of HIV-1-negative men who have sex with men (MSM) for the identification of cases of acute HIV-1 infection (AHI) at Beijing Youan Hospital, Capital Medical University. Individuals with AHI were selected at random. Matched samples were also collected and analyzed from the same patients with chronic HIV-1 infection. None of the study subjects received antiretroviral therapy during acute or chronic infection. Multicolor flow cytometry was used for the immunophenotypic and functional characterization of cTfh cell and B cell subsets. AHI resulted in increased proportions in bulk cTfh, ICOS+cTfh or IL-21+ICOS+cTfh cells. In both acute and chronic infections, activated memory (AM), tissue-like memory (TLM), and plasmablast (PB) B cell levels were increased whilst resting memory (RM) and naïve mature (NM) B cell levels were decreased. Classical memory (CM) B cells were unaffected during infection. Association analyses showed that the levels of ICOS+cTfh and IL-21+ICOS+cTfh cells were negatively correlated with those of AM, CM, RM cells, and positively correlated with those of NM cells in AHI but not chronic HIV-1 infection stage (CHI). Moreover, the frequency of IL-21+ICOS+cTfh cells was also positively correlated with plasma HIV-1 viral load, and had an opposite association trend with CD4+T cell count in AHI. Our data suggests that HIV-1 infection drives the expansion of cTfh cells, which in turn leads to perturbations of B cell differentiation through ICOS signaling during acute infection stage. These findings provide insight on the role of ICOS in the regulation of cTfh/B cell interaction during AHI and may potentially guide the design of effective strategies for restoring anti-HIV-1 immunity in the infected patients.

ObjectiveTo investigate the characteristics and mechanism of the dynamics of HBV infection with the progression of HIV disease and to explore the different responses of T lymphocytes to HBV in HIV patients in different stages of disease.MethodsWe compared the rates and characteristics of HBV coinfection between 372 early HIV-infected and 306 chronically HIV-infected men who have sex with men (MSM) in the Beijing Youan Hospital from October 2006 to November 2014. We further analysed IFN-γ-producing HBV-specific CD8+ T cells in 15 early HIV-infected individuals and 20 chronic HIV-infected individuals with HBV coinfection.ResultsTwenty-three HBsAg-positive cases were detected among the 372 early HIV-infected patients of this cohort, and the coinfection rate was 6.18%, while 35 HBsAg-positive cases were detected among the 306 chronically HIV-infected patients, with a coinfection rate of 11.44%. The coinfection rate of the chronically HIV-infected patients was significantly higher than that of the early-infected patients (p=0.0005). The median CD4+ T cell count in the early HIV infection patients was 445 cells/μL (196-1,030 cells/μL), which was higher than that in the chronic HIV infection patients [358 cells/μL (17-783 cells/μL)] (p<0.001). The proportion of IFN-γ-producing CD8+ T cells in early HIV-infected patients was significantly higher than that in chronically HIV-infected patients.ConclusionThe coinfection rate of HBV in HIV patients increases with HIV disease progression, which might be related to the decreased IFN-γ-producing HBV-specific CD8+ T cell numbers. The closely monitored HBV serum markers from the early stage of HIV infection are warranted.

•Albuvirtide (ABT) is a novel long-acting HIV fusion inhibitor.•ABT combined with LPV/r was non-inferior to LPV/r based three-drug regimen.•ABT combined with LPV/r showed a good safety profile.•ABT combined with LPV/r showed a trend of improvement in renal function.•ABT might be an interesting alternative option for HIV treatment and prevention.