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

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.