Immunological predictors of CD4<sup>+ </sup>T cell decline in antiretroviral treatment interruptions

<p>Abstract</p> <p>Background</p> <p>The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4<sup>+</sup>, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify pred...

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Main Authors: Gonzalez-García Juan, Rubio Rafael, Moreno Ana, de Quiros Juan, Moreno Santiago, Resino Salvador, Seoane Elena, Arribas José, Pulido Federico, Muñoz-Fernández Ma Ángeles
Format: Article
Language:English
Published: BMC 2008-02-01
Series:BMC Infectious Diseases
Online Access:http://www.biomedcentral.com/1471-2334/8/20
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Summary:<p>Abstract</p> <p>Background</p> <p>The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4<sup>+</sup>, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4<sup>+ </sup>cell count declines to < 350/μL in CD4-guided antiretroviral treatment interruptions.</p> <p>Methods</p> <p>27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4<sup>+ </sup>count > 600/μL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4<sup>+ </sup>cell count to < 350/μL.</p> <p>Results</p> <p>After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4<sup>+ </sup>cell count to < 350/μL. Patients with a CD4<sup>+ </sup>nadir of < 200 cells/μL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to <it>Mycobacterium tuberculosis </it>purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4<sup>+ </sup>cell count to < 350/μL.</p> <p>Conclusion</p> <p>Both the number (CD4<sup>+ </sup>nadir) and the functional activity of CD4<sup>+ </sup>(lymphoproliferative response to PPD) predict the CD4<sup>+ </sup>decrease associated with discontinuation of ART in patients with controlled viremia.</p>
ISSN:1471-2334