Human immunodeficiency virus type 1 (HIV-1) persists in a latent reservoir of infected resting memory CD4 cells in patients receiving antiretroviral therapy. We assessed whether multitarget therapy with enfuvirtide, 2 reverse-transcriptase inhibitors, and a ritonavir-boosted protease inhibitor leads to decay of this reservoir. Nineteen treatment-naive patients initiated this regimen; 9 experienced virologic suppression and continued enfuvirtide-containing therapy for at least 48 weeks. In enfuvirtide-treated patients with virological suppression, there was no decay of the latent reservoir (95% confidence interval for half-life, 11 months to infinity). The stability of the latent reservoir despite intensive therapy suggests that new strategies are needed to eradicate HIV-1 from this reservoir. (ClinicalTrials.gov identifier: NCT00051831 .).
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http://dx.doi.org/10.1086/649569 | DOI Listing |
PLoS Pathog
January 2025
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
The latent viral reservoir remains the major barrier to HIV cure, placing the burden of strict adherence to antiretroviral therapy (ART) on people living with HIV to prevent recrudescence of viremia. For infants with perinatally acquired HIV, adherence is anticipated to be a lifelong need. In this study, we tested the hypothesis that administration of ART and viral Envelope-specific rhesus-derived IgG1 monoclonal antibodies (RhmAbs) with or without the IL-15 superagonist N-803 early in infection would limit viral reservoir establishment in SIV-infected infant rhesus macaques.
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January 2025
National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518112, Guangdong Province, China.
Early antiretroviral therapy (ART) initiation is known to limit the establishment of the HIV reservoir, with studies suggesting benefits such as a reduced number of infected cells and a smaller latent reservoir. However, the long-term impact of early ART initiation on the dynamics of the infected cell pool remains unclear, and clinical evidence directly comparing proviral integration site counts between early and late ART initiation is limited. In this study, we used Linear Target Amplification-PCR (LTA-PCR) and Next Generation Sequencing to compare unique integration site (UIS) clonal counts between individuals who initiated ART during acute HIV infection stage (Acute-ART group) and those in the AIDS stage (AIDS-ART group).
View Article and Find Full Text PDFCytotoxic T-lymphocytes (CTL) exert sustained pressure on reservoirs of HIV-infected cells that persist through years of antiretroviral therapy (ART). This selects for latently infected cells, but also potentially for cells that express HIV but possess intrinsic CTL resistance. We demonstrate that such resistance exists in HIV-infected CD4 T-cells that survive rigorous CTL attack and map CTL susceptibility to cell identities and states defined by single-cell multi-omics and functional metabolic profiling.
View Article and Find Full Text PDFiScience
December 2024
Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada.
Latent viral reservoirs (VRs) represent a main barrier to HIV cure. Thus, developing new approaches that can purge and eliminate VRs paves the path toward achieving an HIV-1 cure. APG-1387, a bivalent SMAC mimetic (SM), efficiently reactivates latent HIV expression in T cell line models and enhances active caspase 3 expression, a condition that typically leads to apoptosis.
View Article and Find Full Text PDFEpigenetics Chromatin
January 2025
Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
Despite significant advances in HIV treatment, a definitive cure remains elusive. The first-in-human clinical trial of Excision BioTherapeutics' CRISPR-based HIV cure, EBT-101, demonstrated safety but failed to prevent viral rebound. These outcomes may result from the interplay of several factors.
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