Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues.
Antiretroviral therapy can reduce HIV-1 to undetectable levels in peripheral blood, but the effectiveness of treatment in suppressing replication in lymphoid tissue reservoirs has not been determined. Here we show in lymph node samples obtained before and during 6 mo of treatment that the tissue concentrations of five of the most frequently used antiretroviral drugs are much lower than in peripheral blood. These lower concentrations correlated with continued virus replication measured by the slower decay or increases in the follicular dendritic cell network pool of virions and with detection of viral RNA in productively infected cells. The evidence of persistent replication associated with apparently suboptimal drug concentrations argues for development and evaluation of novel therapeutic strategies that will fully suppress viral replication in lymphatic tissues. These strategies could avert the long-term clinical consequences of chronic immune activation driven directly or indirectly by low-level viral replication to thereby improve immune reconstitution.
Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198.
Courtney V
CV
Fletcher
Kathryn
K
Staskus
Stephen W
SW
Wietgrefe
Meghan
M
Rothenberger
Cavan
C
Reilly
Jeffrey G
JG
Chipman
Greg J
GJ
Beilman
Alexander
A
Khoruts
Ann
A
Thorkelson
Thomas E
TE
Schmidt
Jodi
J
Anderson
Katherine
K
Perkey
Mario
M
Stevenson
Alan S
AS
Perelson
Daniel C
DC
Douek
Ashley T
AT
Haase
Timothy W
TW
Schacker
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006207:Half-Life; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism*; D008297:Male; D014779:Virus Replication; D055815:Young Adult
D019380:Anti-HIV Agents
FDC network; drug levels; pharmacokinetics