Opioid use does not limit potent low-dose HIV-1 latency reversal agent boosting.
medRxiv
; 2023 Jun 03.
Article
en En
| MEDLINE
| ID: mdl-37398278
ABSTRACT
The combined effects of the HIV-1 and opioid epidemics on virus reservoir dynamics are less well characterized. To assess the impact of opioid use on HIV-1 latency reversal, we studied forty-seven suppressed participants with HIV-1 and observed that lower concentrations of combination latency reversal agents (LRA) led to synergistic virus reactivation ex vivo, regardless of opioid use. The use of a Smac mimetic or low-dose protein kinase C agonist, compounds that did not reverse latency alone, in combination with low-dose histone deacetylase inhibitors generated significantly more HIV-1 transcription than phorbol 12-myristate 13-acetate (PMA) with ionomycin, the maximal known HIV-1 reactivator. This LRA boosting did not differ by sex or race and associated with greater histone acetylation in CD4+ T cells and modulation of T cell phenotype. Virion production and the frequency of multiply spliced HIV-1 transcripts did not increase, suggesting a post-transcriptional block still limits potent HIV-1 LRA boosting.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
MedRxiv
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos