Mass spectrometry imaging reveals heterogeneous efavirenz distribution within putative HIV reservoirs

Abstract

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.

Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Figures

FIG 1

EFV distribution in macaque reservoir sites. Representative MSI images are shown on the left, with adjacent CD3+ cell staining of serial colon (A), ileum (B), inguinal lymph node (C), cerebellum (D), and spleen (E) tissue slices. MSI signal intensity is shown next to each image on a concentration-dependent scale. The bottom of the scale (0) represents the presence of no EFV, while the top of the scale reflects the highest per-voxel EFV signal observed within each slice. Brighter colors represent higher EFV concentrations.