Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study.
Am J Transplant
; 21(5): 1765-1779, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-32780519
Pharmacologic inhibition of the mammalian target of rapamycin (mTOR) in the setting of renal transplantation has previously been associated with lower human immunodeficiency virus 1 (HIV-1) DNA burden, and in vitro studies suggest that mTOR inhibition may lead to HIV transcriptional silencing. Because prospective clinical trials are lacking, we conducted an open-label, single-arm study to determine the impact of the broad mTOR inhibitor, everolimus, on residual HIV burden, transcriptional gene expression profiles, and immune responses in HIV-infected adult solid organ transplant (SOT) recipients on antiretroviral therapy. Whereas everolimus therapy did not have an overall effect on cell-associated HIV-1 DNA and RNA levels in the entire cohort, participants who maintained everolimus time-averaged trough levels >5 ng/mL during the first 2 months of therapy had significantly lower RNA levels up to 6 months after the cessation of study drug. Time-averaged everolimus trough levels significantly correlated with greater inhibition of mTOR gene pathway transcriptional activity. Everolimus treatment also led to decreased PD-1 expression on certain T cell subsets. These data support the rationale for further study of the effects of mTOR inhibition on HIV transcriptional silencing in non-SOT populations, either alone or in combination with other strategies. Trial Registration: ClinicalTrials.gov NCT02429869.
Palabras clave
clinical research/practice; immunosuppressant - mechanistic target of rapamycin: everolimus; immunosuppression/immune modulation; infection and infectious agents - viral: human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS); infectious disease; organ transplantation in general; translational research/science
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Preparaciones Farmacéuticas
/
Trasplante de Órganos
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos