PMID- 32780519
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 21
IP  - 5
DP  - 2021 May
TI  - Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received 
      solid organ transplantation: A prospective study.
PG  - 1765-1779
LID - 10.1111/ajt.16244 [doi]
AB  - 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.
CI  - (c) 2020 The American Society of Transplantation and the American Society of 
      Transplant Surgeons.
FAU - Henrich, Timothy J
AU  - Henrich TJ
AUID- ORCID: 0000-0002-6684-0622
AD  - Division of Experimental Medicine, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Schreiner, Corinna
AU  - Schreiner C
AD  - Division of Experimental Medicine, University of California San Francisco, San 
      Francisco, California, USA.
AD  - Institute of Biochemistry and Molecular Biology, Ulm University, Ulm, Germany.
FAU - Cameron, Cheryl
AU  - Cameron C
AD  - Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA.
FAU - Hogan, Louise E
AU  - Hogan LE
AD  - Division of Experimental Medicine, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Richardson, Brian
AU  - Richardson B
AD  - Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA.
FAU - Rutishauser, Rachel L
AU  - Rutishauser RL
AD  - Division of Experimental Medicine, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Deitchman, Amelia N
AU  - Deitchman AN
AD  - Department of Clinical Pharmacy, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Chu, Simon
AU  - Chu S
AD  - Department of Surgery, University of California San Francisco, San Francisco, 
      California, USA.
FAU - Rogers, Rodney
AU  - Rogers R
AD  - Department of Surgery, University of California San Francisco, San Francisco, 
      California, USA.
FAU - Thanh, Cassandra
AU  - Thanh C
AD  - Division of Experimental Medicine, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Gibson, Erica A
AU  - Gibson EA
AD  - Division of Experimental Medicine, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Zarinsefat, Arya
AU  - Zarinsefat A
AD  - Department of Surgery, University of California San Francisco, San Francisco, 
      California, USA.
FAU - Bakkour, Sonia
AU  - Bakkour S
AD  - Vitalant Research Institute, San Francisco, California, USA.
FAU - Aweeka, Francesca
AU  - Aweeka F
AD  - Department of Clinical Pharmacy, University of California San Francisco, San 
      Francisco, California, USA.
FAU - Busch, Michael P
AU  - Busch MP
AD  - Vitalant Research Institute, San Francisco, California, USA.
FAU - Liegler, Teri
AU  - Liegler T
AD  - Division of HIV, Infectious Diseases & Global Medicine, University of California 
      San Francisco, San Francisco, California, USA.
FAU - Baker, Christopher
AU  - Baker C
AD  - Division of HIV, Infectious Diseases & Global Medicine, University of California 
      San Francisco, San Francisco, California, USA.
FAU - Milush, Jeffrey
AU  - Milush J
AD  - Division of HIV, Infectious Diseases & Global Medicine, University of California 
      San Francisco, San Francisco, California, USA.
FAU - Deeks, Steven G
AU  - Deeks SG
AD  - Division of HIV, Infectious Diseases & Global Medicine, University of California 
      San Francisco, San Francisco, California, USA.
FAU - Stock, Peter G
AU  - Stock PG
AUID- ORCID: 0000-0002-5806-0167
AD  - Department of Surgery, University of California San Francisco, San Francisco, 
      California, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02429869
GR  - K23 AI134327/AI/NIAID NIH HHS/United States
GR  - 109301/WT_/Wellcome Trust/United Kingdom
GR  - L30 AI147223/AI/NIAID NIH HHS/United States
GR  - T32 AI125222/AI/NIAID NIH HHS/United States
GR  - K23AI134327/NIH/NIAID/
GR  - P30 AI027763/AI/NIAID NIH HHS/United States
GR  - R01 AI122862/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200915
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Pharmaceutical Preparations)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Adult
MH  - Everolimus/therapeutic use
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - *Organ Transplantation
MH  - *Pharmaceutical Preparations
MH  - Prospective Studies
PMC - PMC9177122
MID - NIHMS1810885
OTO - NOTNLM
OT  - clinical research/practice
OT  - immunosuppressant - mechanistic target of rapamycin: everolimus
OT  - immunosuppression/immune modulation
OT  - infection and infectious agents - viral: human immunodeficiency virus 
      (HIV)/acquired immunodeficiency syndrome (AIDS)
OT  - infectious disease
OT  - organ transplantation in general
OT  - translational research/science
EDAT- 2020/08/12 06:00
MHDA- 2021/06/22 06:00
PMCR- 2022/06/08
CRDT- 2020/08/12 06:00
PHST- 2020/06/30 00:00 [revised]
PHST- 2020/05/03 00:00 [received]
PHST- 2020/07/19 00:00 [accepted]
PHST- 2020/08/12 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/08/12 06:00 [entrez]
PHST- 2022/06/08 00:00 [pmc-release]
AID - S1600-6135(22)08540-9 [pii]
AID - 10.1111/ajt.16244 [doi]
PST - ppublish
SO  - Am J Transplant. 2021 May;21(5):1765-1779. doi: 10.1111/ajt.16244. Epub 2020 Sep 
      15.