Mass spectrometry imaging reveals heterogeneous efavirenz distribution within putative HIV reservoirs.
Persistent HIV replication within active viral reservoirs may be caused by inadequate antiretroviral penetration. Here, we used mass spectrometry imaging with infrared matrix-assisted laser desorption-electrospray ionization to quantify the distribution of efavirenz within tissues from a macaque dosed orally to a steady state. Intratissue efavirenz distribution was heterogeneous, with the drug concentrating in the lamina propria of the colon, the primary follicles of lymph nodes, and the brain gray matter. These are the first imaging data of an antiretroviral drug in active viral reservoirs.
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Corbin G
CG
Thompson
W. M. Keck FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.
Mark T
MT
Bokhart
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Craig
C
Sykes
University of California, Davis, California, USA.
Lourdes
L
Adamson
School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Yuri
Y
Fedoriw
University of California, Davis, California, USA.
Paul A
PA
Luciw
W. M. Keck FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.
David C
DC
Muddiman
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Angela D M
AD
Kashuba
W. M. Keck FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA erosen@ncsu.edu.
Elias P
EP
Rosen
D000480:Alkynes; D000818:Animals; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D066128:Gray Matter / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008251:Macaca; D013058:Mass Spectrometry / Q000379:methods*
D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz