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Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.
Nat Med
January 2025
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.
View Article and Find Full Text PDFRev-RRE activity modulates HIV-1 replication and latency reactivation: Implications for viral persistence and cure strategies.
bioRxiv
January 2025
Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.
The HIV-1 Rev-RRE regulatory axis plays a crucial role in viral replication by facilitating the nucleo-cytoplasmic export and expression of viral mRNAs with retained introns. In this study, we investigated the impact of variation in Rev-RRE functional activity on HIV-1 replication kinetics and reactivation from latency. Using a novel HIV-1 clone with an interchangeable Rev cassette, we engineered viruses with different Rev functional activities and demonstrated that higher Rev-RRE activity confers greater viral replication capacity while maintaining a constant level of Nef expression.
View Article and Find Full Text PDFThe Importance of Clinical History in the Etiological Diagnosis of Diffuse Alveolar Hemorrhage Associated With Improper Adrenaline Use.
Cureus
December 2024
Department of Intensive Care Medicine, Centro Hospitalar Universitário de São João, Porto, PRT.
This case involves a 21-year-old male healthcare student with a medical history of HIV-1 infection for two years and anxiety disorder. He presented to the emergency department with hemoptysis and dyspnea of sudden onset. A thoracic CT scan revealed multiple bilateral nodular ground-glass opacities suggestive of diffuse alveolar hemorrhage (DAH).
View Article and Find Full Text PDFNo virological failure in patients living with HIV with past NNRTI resistance-associated mutations switched to doravirine-containing regimens.
J Antimicrob Chemother
January 2025
Sorbonne University, Infectious Diseases Department, Pitié-Salpêtrière hospital, AP-HP, Pierre Louis Institute of Epidemiology and Public Health (iPLESP), INSERM U1136, Paris, France.
Background: Doravirine is licensed in patients living with HIV (PWH) harbouring no prior resistance to any NNRTIs. We aimed to evaluate in real life the efficacy of doravirine with prior NNRTI virological failure and NNRTI resistance-associated mutations (RAMs).
Methods: This observational study included PWH switched to a doravirine-containing regimen between 30 September 2019 and 1 May 2022, with an HIV-1 RNA of ≤50 copies/mL and past NNRTI-RAMs.
HIV-1 DNA Genotypic Drug Resistance Testing Guides Antiretroviral Therapy in Patients with Low-Level Viremia.
AIDS Res Hum Retroviruses
January 2025
Department of Infectious Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
In 2023, we published a case study involving a 10-year-old HIV-1-infected child with low-level viremia (LLV). We showed that this child patient achieved successful viral suppression by modifying the antiretroviral therapy (ART) regimen according to the HIV-1 DNA genotypic drug resistance testing. In this study, we aimed to address whether HIV-1 DNA genotypic drug resistance testing could direct successfully virological suppression in HIV-1-infected patients experiencing persistent LLV based on evidence from a cohort study.
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