HIV-specific CD4+ T cells may contribute to viral persistence in HIV controllers.
BACKGROUND
Human immunodeficiency virus (HIV)--infected individuals maintaining plasma HIV RNA levels <75 copies/mL in the absence of therapy ("HIV controllers") often maintain high HIV-specific T cell responses, which likely contribute to the control of viral replication. Despite robust immune responses, these individuals never eradicate HIV infection. We hypothesized that HIV-specific CD4(+) T cells might serve as target cells for HIV, contributing to viral persistence in this setting.


METHODS
We measured frequencies of activated (CD38(+) HLA-DR(+)) and HIV Gag-specific CD4(+) and CD8(+) T cells and plasma- and cell-associated levels of HIV RNA and DNA in a cohort of 38 HIV controllers.


RESULTS
Although there was no evidence of a relationship between the extent of low-level viremia and the frequency of either activated or HIV-specific CD4(+) T cells, controllers with higher HIV-specific CD4(+) T cell frequencies had higher cell-associated HIV DNA levels (ρ = 0.53; P = .019). Higher activated CD4+ T cell frequencies were also associated with higher levels of cell-associated DNA (P = .027) and RNA (P = .0096). However, there was no evidence of a relationship between cell-associated HIV RNA or DNA levels and HIV-specific CD8(+) T cell frequencies.


CONCLUSIONS
These data support a model in which strong HIV-specific CD4(+) T cell responses in HIV controllers, while contributing to a potent adaptive immune response, may also contribute to viral persistence, preventing the natural eradication of HIV infection.
Department of Medicine, University of California, San Francisco, California, USA. phunt@php.ucsf.edu
Peter W
PW
Hunt
Hiroyu
H
Hatano
Elizabeth
E
Sinclair
Tzong-Hae
TH
Lee
Michael P
MP
Busch
Jeffrey N
JN
Martin
Joseph M
JM
McCune
Steven G
SG
Deeks
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D004279:DNA, Viral; D006684:HLA-DR Antigens; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; D051997:ADP-ribosyl Cyclase 1
AIDS. 2008 Jul 11;22(11):1313-22
18580611
J Infect Dis. 2008 Jan 1;197(1):126-33
18171295
J Infect Dis. 2009 May 1;199(9):1318-22
19301980
Nature. 2002 May 2;417(6884):95-8
11986671
J Immunol. 2005 Nov 1;175(9):6117-22
16237108
Clin Exp Immunol. 2006 Mar;143(3):435-44
16487242
J Virol. 2008 Aug;82(15):7395-410
18495769
J Virol. 2007 Dec;81(24):13904-15
17928341
Retrovirology. 2006 Jun 22;3:35
16792805
PLoS One. 2008;3(11):e3636
18982067
Lancet. 2008 Nov 29;372(9653):1881-1893
19012954
Nature. 2009 Apr 23;458(7241):1034-8
19262509
J Virol. 2008 Jun;82(11):5398-407
18353945
Immunity. 2008 Dec 19;29(6):1009-21
19062316
AIDS. 2009 Jun 1;23(9):1059-67
19390417
J Infect Dis. 2008 Feb 15;197(4):563-71
18275276
J Virol. 2009 Mar;83(6):2743-55
19116253
AIDS. 2007 May 11;21(8):1043-5
17457100
J Med Virol. 1995 Jun;46(2):116-21
7636497
PLoS Pathog. 2009 Apr;5(4):e1000377
19360131
Hepatology. 2008 May;47(5):1446-52
18220272
J Virol. 2009 Jan;83(1):329-35
18945778
Clin Immunol. 2001 Feb;98(2):200-11
11161976
J Infect Dis. 2010 Sep 1;202(5):705-16
20662716
Clin Infect Dis. 2005 Oct 1;41(7):1053-6
16142675
J Virol. 2005 Nov;79(22):14169-78
16254352
Science. 2007 Aug 17;317(5840):944-7
17641165
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6776-81
17428922
J Infect Dis. 2003 May 15;187(10):1534-43
12721933
Blood. 2006 Jun 15;107(12):4781-9
16467198
N Engl J Med. 2004 Aug 19;351(8):760-8
15317889
AIDS. 1991 Oct;5(10):1201-7
1786148
Blood. 2004 Feb 1;103(3):966-72
12958069
AIDS. 2000 Dec 22;14(18):2823-9
11153663
J Virol. 2007 Mar;81(5):2508-18
17151109
Transfusion. 2005 Aug;45(8):1280-90
16078913
J Virol. 2009 Jan;83(1):88-97
18945771
J Infect Dis. 2009 Feb 1;199(3):419-26
19115949
Nat Genet. 2007 Jun;39(6):733-40
17496894
Clin Infect Dis. 2010 Jul 15;51(2):233-8
20550452
AIDS. 2009 Jan 2;23(1):19-28
19050382
Transfusion. 2005 Dec;45(12):1853-63
16371038