Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study

Am J Transplant. 2021 May;21(5):1765-1779. doi: 10.1111/ajt.16244. Epub 2020 Sep 15.


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.

Keywords: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Everolimus / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Mechanistic Target of Rapamycin Complex 1
  • Organ Transplantation*
  • Pharmaceutical Preparations*
  • Prospective Studies


  • Immunosuppressive Agents
  • Pharmaceutical Preparations
  • Everolimus
  • Mechanistic Target of Rapamycin Complex 1

Associated data

  • ClinicalTrials.gov/NCT02429869