Targeting the HIV reservoir: chimeric antigen receptor therapy for HIV cure / 中华医学杂志(英文版)

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.

Hospital contact patterns and vulnerability to SARS-CoV-2 outbreaks

The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). Heterogeneity of risk across wards is still poorly described. We measured CPIs in 15 clinical wards across three hospitals using wearable sensors over 36 hours in spring 2020. This data was combined with a transmission model to estimate and compare transmission risks across wards. We found a four-fold range of epidemic risk between wards, with patients frequently presenting high risk to patients and healthcare workers (HCWs). Using a simulation study, we then assessed the potential impact on global risk of targeting individuals for prevention based on their contact patterns. We found that targeting individuals with the highest cumulative contact hours was most impactful. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk. One Sentence SummaryWe measured contacts between staff, patients and visitors in 15 hospital wards, and used models to predict epidemic risk and evaluate interventions.