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.
Clin Infect Dis
; 74(11): 2044-2049, 2022 06 10.
Article
em En
| MEDLINE
| ID: mdl-34436569
ABSTRACT
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 (Pâ =â .008, median fold change (mfc)â =â 0.8) and a lower median level of intact HIV DNA (Pâ =â not significant [n.s.], mfcâ =â 0.8) after ABX464 treatment. Moreover, we observed a decrease in initiated HIV RNA per million CD4+ T cells and per provirus (Pâ =â .05, mfcâ =â 0.7; Pâ =â .004, mfcâ =â 0.5, respectively), a trend toward a decrease in the 5'elongated HIV RNA per provirus (Pâ =â .07, mfcâ =â 0.5), and a lower median level of unspliced HIV RNA (Pâ =â n.s., mfcâ =â 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. CLINICAL TRIALS REGISTRATION NCT02990325.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
Limite:
Humans
Idioma:
En
Revista:
Clin Infect Dis
Ano de publicação:
2022
Tipo de documento:
Article