Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy.
OBJECTIVE
To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut.


METHODS
Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml.


METHODS
Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers.


RESULTS
Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 10 CD4(+) T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8(+) T cells in the ileum and PBMC, and a trend towards increased CD4(+) T cells in the ileum.


CONCLUSIONS
Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.
Yukl
Steven A
SA
San Francisco VA Medical Center (SFVAMC) and University of California, San Francisco (UCSF), San Francisco, California, USA. steven.yukl@ucsf.edu
Shergill
Amandeep K
AK
McQuaid
Kenneth
K
Gianella
Sara
S
Lampiris
Harry
H
Hare
C Bradley
CB
Pandori
Mark
M
Sinclair
Elizabeth
E
Günthard
Huldrych F
HF
Fischer
Marek
M
Wong
Joseph K
JK
Havlir
Diane V
DV
D000293:Adolescent; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage*; D012367:RNA, Viral / Q000276:immunology*; D000068898:Raltegravir Potassium; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium
J Virol Methods. 2007 Apr;141(1):49-57
17184853
J Virol Methods. 2007 Dec;146(1-2):236-45
17707519
Methods Mol Biol. 2009;485:347-56
19020836
J Infect Dis. 2004 Dec 1;190(11):1979-88
15529263
Nat Rev Microbiol. 2008 Nov;6(11):815-26
18923409
J Acquir Immune Defic Syndr. 2004 Jan 1;35(1):33-7
14707789
Biol Chem. 2008 Oct;389(10):1253-60
18713012
Immunol Today. 1998 Nov;19(11):528-32
9818549
AIDS. 1994 Jun;8(6):719-31
8086128
Retrovirology. 2008 Nov 26;5:107
19036147
J Infect Dis. 2003 May 15;187(10):1534-43
12721933
Clin Immunol. 2008 Mar;126(3):315-21
17997138
J Clin Invest. 2004 Sep;114(5):605-10
15343375
J Infect Dis. 2008 Jan 1;197(1):126-33
18171295
J Virol. 2007 Sep;81(18):9693-706
17609262
J Virol Methods. 2001 Jun;95(1-2):65-79
11377714
J Virol. 2003 Oct;77(20):11212-9
14512569
J Virol. 2007 Jun;81(11):5460-71
17344302
AIDS. 2008 Sep 12;22(14):1880-2
18753926
J Infect Dis. 2008 Feb 1;197(3):411-9
18248304
J Infect Dis. 2004 Apr 15;189(8):1452-65
15073683
J Clin Invest. 2005 Nov;115(11):3250-5
16276421
Retrovirology. 2007 Aug 29;4:60
17727722
Immunity. 2002 Jan;16(1):145-55
11825573
Retrovirology. 2009 Oct 13;6:89
19825175
J Virol Methods. 2010 Dec;170(1-2):115-20
20863855
J Infect Dis. 2010 Nov 15;202(10):1553-61
20939732
J Virol Methods. 2010 May;165(2):151-60
20116399
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16725-30
18936487
Curr Opin HIV AIDS. 2009 Mar;4(2):143-9
19339954
Nat Med. 1999 Oct;5(10):1099-104
10502799
Nat Med. 2000 Jan;6(1):76-81
10613828
Traffic. 2004 Sep;5(9):643-50
15296489
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9403-8
19470482
J Virol. 2004 Jan;78(2):968-79
14694128
Clin Infect Dis. 2010 Mar 15;50(6):912-9
20156060
J Clin Microbiol. 1999 May;37(5):1260-4
10203467
J Infect Dis. 2008 Mar 1;197(5):714-20
18260759
J Virol. 2009 Jun;83(12):6234-46
19369333