ABX464 Decreases the Total Human Immunodeficiency Virus (HIV) Reservoir and HIV Transcription Initiation in CD4+ T Cells From Antiretroviral Therapy-Suppressed Individuals Living With HIV
| Autor: | Moron-Lopez, S, Bernal, S, Wong, JK, Martinez-Picado, J, Yukl, SA |
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| Rok vydání: | 2022 |
| Předmět: |
CD4-Positive T-Lymphocytes
Clinical Trials and Supportive Activities HIV Infections ABX464 DNA HIV-1 transcription Viral Load HIV-1 DNA Biological Sciences Medical and Health Sciences Microbiology antiviral drugs Infectious Diseases Proviruses Clinical Research HIV-1 Quinolines Genetics Humans RNA HIV/AIDS HIV-1 RNA Viral Infection |
| Zdroj: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol 74, iss 11 Clinical Infectious Diseases r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname |
| ISSN: | 1058-4838 |
| Popis: | We evaluated the effect of ABX464 on the human immunodeficiency virus (HIV) reservoir and on the HIV transcription profile. ABX464 decreases total HIV DNA, may decrease intact HIV DNA, decreases HIV transcriptional initiation, and may decrease HIV transcriptional elongation. Background Antiretroviral therapy (ART) intensification and disruption of latency have been suggested as strategies to eradicate HIV. ABX464 is a novel antiviral that inhibits HIV RNA biogenesis. We investigated its effect on HIV transcription and total and intact HIV DNA in CD4(+) T cells from ART-suppressed participants enrolled in the ABIVAX-005 clinical trial (NCT02990325). Methods Peripheral CD4(+) T cells were available for analysis from 9 ART-suppressed participants who were treated daily with 150 mg of ABX464 for 4 weeks. Total and intact HIV DNA and initiated, 5'elongated, unspliced, polyadenylated, and multiply-spliced HIV transcripts were quantified at weeks 0, 4, and 8 using ddPCR. Results We observed a significant decrease in total HIV DNA (P = .008, median fold change (mfc) = 0.8) and a lower median level of intact HIV DNA (P = not significant [n.s.], mfc = 0.8) after ABX464 treatment. Moreover, we observed a decrease in initiated HIV RNA per million CD4(+) T cells and per provirus (P = .05, mfc = 0.7; P = .004, mfc = 0.5, respectively), a trend toward a decrease in the 5'elongated HIV RNA per provirus (P = .07, mfc = 0.5), and a lower median level of unspliced HIV RNA (P = n.s., mfc = 0.6), but no decrease in polyadenylated or multiply-spliced HIV RNA. Conclusions In this substudy, ABX464 had a dual effect of decreasing total HIV DNA (and possibly intact proviruses) and HIV transcription per provirus. To further characterize its specific mechanism of action, long-term administration of ABX464 should be studied in a larger cohort. |
| Databáze: | OpenAIRE |
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