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hiv reservoir: antiviral immune responses and immune interventions for curing hiv infection

Chinese Medical Journal 2022年第22期135卷 2667-2676页

作者： Shuang Li Christiane Moog Tong Zhang Bin Su Beijing Key Laboratory for hiv/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Laboratoire d’ImmunoRhumatologie Moléculaire Institut national de la santéet de la recherche médicale(INSERM)UMR_S 1109Institut thématique interdisciplinaire(ITI)de Médecine de Précision de StrasbourgTransplantex NGFacultéde MédecineFédération Hospitalo-Universitaire OMICAREFédération de Médecine Translationnelle de Strasbourg(FMTS)Universitéde StrasbourgStrasbourg 67000France

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.

关键词： Antiviral immune response Functional hiv cure hiv reservoir Human immunodeficiency virus Immune interventions

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Targeting the hiv reservoir:chimeric antigen receptor therapy for hiv cure

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Chinese Medical Journal 2023年第22期136卷 2658-2667页

作者： Shuang Li Hu Wang Na Guo Bin Su Olivier Lambotte Tong Zhang Beijing Key Laboratory for hiv/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Department of Internal Medicine AP-HPBicêtre HospitalUMR1184 INSERM CEALe Kremlin BicêtreUniversity Paris SaclayParis 94270France

Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(hiv)-infected individuals,ART alone cannot completely eliminate hiv due to its integration into the host cell genome to form viral reservoirs.To achieve a functional cure for hiv infection,numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate hiv reservoirs in the absence of ART.Early studies have tested adoptive T-cell therapies in hiv-infected individuals,but their effectiveness was limited.In recent years,with the technological progress and great success of chimeric antigen receptor(CAR)therapy in the treatment of hematological malignancies,CAR therapy has gradually shown its advantages in the field of hiv infection.Many studies have identified a variety of hiv-specific CAR structures and types of cytolytic effector cells.Therefore,CAR therapy may be beneficial for enhancing hiv immunity,achieving hiv control,and eliminating hiv reservoirs,gradually becoming a promising strategy for achieving a functional hiv cure.In this review,we provide an overview of the design of anti-hiv CAR proteins,the cell types of anti-hiv CAR(including CAR T cells,CAR natural killer cells,and CAR-encoding hematopoietic stem/progenitor cells),the clinical application of CAR therapy in hiv infection,and the prospects and challenges in anti-hiv CAR therapy for maintaining viral suppression and eliminating hiv reservoirs.

关键词： Functional hiv cure hiv reservoir Chimeric antigen receptor therapy CAR T cells CAR natural killer cells

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Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated hiv-1 DNA

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Chinese Medical Journal 2024年第6期137卷 729-736页

作者： Lin Yuan Zhiying Liu Xin Zhang Feili Wei Shan Guo Na Guo Lifeng Liu Zhenglai Ma Yunxia Ji Rui Wang Xiaofan Lu Zhen Li Wei Xia Hao Wu Tong Zhang Bin Su Beijing Key Laboratory for hiv/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical UniversityBeijing 100069China

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,Phiv 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.

关键词： Human immunodeficiency virus hiv Integrated hiv-1 DNA Total hiv DNA Droplet digital polymerase chain reaction hiv reservoir Antiretroviral therapy

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