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  • 1
    In: Journal of Infection, Elsevier BV, Vol. 85, No. 3 ( 2022-09), p. 334-363
    Type of Medium: Online Resource
    ISSN: 0163-4453
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2012883-6
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  • 2
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 133, No. 24 ( 2020-11-25), p. 2919-2927
    Abstract: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. Methods We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for 〉 6 months with a plasma viral load 〉 1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. Results At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. Conclusions The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. Trial registration ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov. Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 3
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 4
    Online Resource
    Online Resource
    Massachusetts Medical Society ; 2019
    In:  New England Journal of Medicine Vol. 381, No. 13 ( 2019-09-26), p. 1240-1247
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 381, No. 13 ( 2019-09-26), p. 1240-1247
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    RVK:
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2019
    detail.hit.zdb_id: 1468837-2
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  • 5
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 12 ( 2021-2-24)
    Abstract: Background: Efavirenz (EFV) is widely used in antiretroviral therapy (ART), but the incidence and risk factors of neuropsychiatric adverse events (NPAEs) after EFV treatment have rarely been studied in Chinese ART naïve patients. Methods: This prospective cohort study assessed HIV-infected patients initiating antiretroviral treatment with EFV to determine prevalence of and factors associated with NPAEs over a 12-month follow-up period using the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). Results: A total of 546 patients were enrolled. Prevalence of anxiety, depression, and sleep disturbances at baseline were 30.4, 22.7, and 68.1%, respectively. Six patients discontinued treatment due to drug related NPAEs. Treatment was associated with improvements in HADS-A, HADS-D, and PSQI scores over the 12-month follow-up, and the frequencies of patients with anxiety, depression, and sleep disturbances significantly decreased after 12 months. Abnormal baseline HADS-A, HADS-D, and PSQI scores and other factors, including high school education or lower income, unemployment, divorce, and WHO III/IV stages, were associated with severe neuropsychiatric disorders over the 12 months. Conclusions: These findings suggested EFV discontinuation due to NAPEs was low, and the HADS-A, HADS-D, and PSQI scores after 12 months of EFV treatment were associated with several risk factors. The clinicians should keep in mind and routinely screen for the risk factors associated with neuropsychiatric disorders in HIV-infected patients.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564218-2
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  • 6
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: This paper introduces a comprehensive case management model uniting doctors, nurses, and non-governmental organizations (NGOs) in order to shorten the time from HIV diagnosis to initiation of antiviral therapy, improve patients’ adherence, and ameliorate antiretroviral treatment (ART)-related outcomes. Methods All newly diagnosed human immunodeficiency virus (HIV) cases at Beijing YouAn Hospital from January 2012 to December 2013 were selected as the control group, while all newly diagnosed HIV-infected patients from January 2015 to December 2016 were selected as the intervention group, receiving the comprehensive case management model. Results 4906 patients were enrolled, of which 1549 were in the control group and 3357 in the intervention group. The median time from confirming HIV infection to ART initiation in the intervention group was 35 (18–133) days, much shorter than the control group (56 (26–253) days, P  〈  0.001). Participants in the intervention group had better ART adherence compared to those in the control group (intervention: 95.3%; control: 89.2%; p  〈  0.001). During the 2 years’ follow-up, those receiving case management were at decreased odds of experiencing virological failure (OR: 0.27, 95%CI: 0.17–0.42, P   〈  0.001). Observed mortality was 0.4 deaths per 100 patient-years of follow-up for patients in the control group compared with 0.2 deaths per 100 patient-years of follow-up in the intervention group. Conclusions People living with HIV engaged in the comprehensive case management model were more likely to initiate ART sooner and maintained better treatment compliance and improved clinical outcomes compared to those who received routine care. A comprehensive case management program could be implemented in hospitals across China in order to reduce the HIV disease burden in the country.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041550-3
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Chinese Medical Journal Vol. 136, No. 4 ( 2022-12-29), p. 433-445
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 4 ( 2022-12-29), p. 433-445
    Abstract: Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low ) or high levels (CD8 high ) on HIV-1 replication inhibition after HIV-1 invasion into individual. Methods: Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 + CD8 low T cells and their counterpart CD3 + CD8 high T cells at different stages of HIV-1 infection. Results: Compared with healthy donors, CD3 + CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 + CD8 low T cells gradually decreased. Simultaneously, CD3 + CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 + CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 − HLA-DR + CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = −0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 + CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 + CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = −0.456, P = 0.043; TIGIT: r = −0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 + CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = −0.578, P = 0.015). Notably, in the first month of AHI, few CD3 + CD8 low T cells, but comparable amounts of CD3 + CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 + CD8 low T cells than CD3 + CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Conclusions: Our findings suggest that CD3 + CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 + CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 + CD8 high T cells.
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 8
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 136, No. 24 ( 2023-12-20), p. 2948-2959
    Abstract: 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. Conclusion: s: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.
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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  • 9
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-2-10)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
    In: Journal of Medical Virology, Wiley, Vol. 95, No. 2 ( 2023-02)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0146-6615 , 1096-9071
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 752392-0
    detail.hit.zdb_id: 1475090-9
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