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Background  The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4 + , but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4 +  cell count declines to < 350/μL in CD4-guided antiretroviral treatment interruptions.    Methods  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 +  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 +  cell count to < 350/μL.    Results  After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4 +  cell count to < 350/μL. Patients with a CD4 +  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  Mycobacterium tuberculosis  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 +  cell count to < 350/μL.    Conclusion  Both the number (CD4 +  nadir) and the functional activity of CD4 +  (lymphoproliferative response to PPD) predict the CD4 +  decrease associated with discontinuation of ART in patients with controlled viremia.

Immunological predictors of CD4+T cell decline in antiretroviral treatment interruptions