A novel chemokine-receptor-5 (CCR5) blocker, SCH532706, has differential effects on CCR5+CD4+ and CCR5+CD8+ T cell numbers in chronic HIV infection

Pett, Sarah L., Zaunders, John, Bailey, Michelle, Murray, John, MacRae, Karen, Emery, Sean, Cooper, David A. and Kelleher, Anthony D. (2010) A novel chemokine-receptor-5 (CCR5) blocker, SCH532706, has differential effects on CCR5+CD4+ and CCR5+CD8+ T cell numbers in chronic HIV infection. Aids Research and Human Retroviruses, 26 6: 653-661. doi:10.1089/aid.2009.0278


Author Pett, Sarah L.
Zaunders, John
Bailey, Michelle
Murray, John
MacRae, Karen
Emery, Sean
Cooper, David A.
Kelleher, Anthony D.
Title A novel chemokine-receptor-5 (CCR5) blocker, SCH532706, has differential effects on CCR5+CD4+ and CCR5+CD8+ T cell numbers in chronic HIV infection
Formatted title
A novel chemokine-receptor-5 (CCR5) blocker, SCH532706, has differential effects on CCR5+CD4+ and CCR5+CD8+ T cell numbers in chronic HIV infection
Journal name Aids Research and Human Retroviruses   Check publisher's open access policy
ISSN 0889-2229
1931-8405
Publication date 2010-06-20
Sub-type Article (original research)
DOI 10.1089/aid.2009.0278
Open Access Status Not yet assessed
Volume 26
Issue 6
Start page 653
End page 661
Total pages 9
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Language eng
Formatted abstract
HIV treatment with CCR5 receptor blockers may impact CCR5+ cell distribution. T cell subsets, plasmacytoid dendritic cells (PDC), and antigen-specific [Mycobacteria tuberculosis/avium (M.TB/MAI), cytomegalovirus (CMV), Herpes simplex (HSV), HIV-Gag] CD4+ T cells were measured in untreated R5-tropic-HIV-infected adults receiving 10 days of SCH532706 (Phase 1), 15 days no therapy, then 10 days of cART (without SCH532706) (Phase 2). Ten males were enrolled with median cells/μl (range) of CD4+ 310 (92-848), CCR5+CD4+ 57 (17-118), CD8+ 895 (459-1666), and CCR5+CD8+ 392 (250-983), and median plasma HIV RNA of 4.6 log10 copies/ml. At baseline, proportions of M.TB, MAI, CMV, HSV, and HIV-Gag-specific CD4+ T cells were 0.3%, 3.0%, 6.0%, 2.0%, and 1.6%, respectively. Median log10 HIV RNA copies/ml declines were 1.5 (Phase 1) and 1.75 (Phase 2) (p=0.7). Median CD4+ and CD8+ changes, respectively, during Phases 1 (+16; +91) and 2 (+28; -71) were similar (p=0.7 both). However, CCR5+CD8+ T cell fluctuations were significantly different (p=0.02) during Phase 1 (+147 cells) vs. Phase 2 (-35 cells). PDC increased significantly more during Phase 1 (p=0.04). Declines in antigen-specific cells were similar except for M. avium, which declined significantly during Phase 2 (p=0.04). Similar declines in activation and proliferation of T cell subsets were observed during both treatment phases. For equivalent HIV RNA declines, CCR5-receptor blockade differentially increased CD8+ T cell and PDC numbers in the circulation. These results confirm that cell surface CCR5 expression on these cells constantly directs trafficking during HIV infection. The persistence and clinical meaning of these immunological changes during long-term exposure to this class of anti-HIV drugs are unknown, but may have implications for immunosurveillance of inflammation.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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