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Everolimus, an mTORC1/2 inhibitor, in ART‐suppressed individuals who received solid organ transplantation: A prospective study
Author(s) -
Henrich Timothy J.,
Schreiner Corinna,
Cameron Cheryl,
Hogan Louise E.,
Richardson Brian,
Rutishauser Rachel L.,
Deitchman Amelia N.,
Chu Simon,
Rogers Rodney,
Thanh Cassandra,
Gibson Erica A.,
Zarinsefat Arya,
Bakkour Sonia,
Aweeka Francesca,
Busch Michael P.,
Liegler Teri,
Baker Christopher,
Milush Jeffrey,
Deeks Steven G.,
Stock Peter G.
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16244
Subject(s) - everolimus , medicine , pi3k/akt/mtor pathway , transplantation , mtorc1 , clinical trial , kidney transplantation , oncology , prospective cohort study , sirolimus , pharmacology , biology , signal transduction , biochemistry
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.