Abstract
BackgroundThe 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.Methods27 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.ResultsAfter 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.ConclusionBoth 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.
Highlights
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 decision to interrupt antiretroviral therapy (ART) was made jointly by the physician and the patient, during two weeks, while an offer to be included in this study was made to all the HIV patient from several different hospitals. 27 patients responded affirmatively and a written informed consent form was obtained from all patients
We looked for functional characteristics of CD4+ T cells that could be associated with the decline of CD4+ count after ART discontinuation
Summary
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. Large clinical trials have concluded that treatment interruptions can no longer be recommended due to the risk of clinical progression in some circumstances [4] Other studies, both retrospective and prospective, carried out under different conditions, have reached different conclusions [5,6]. In these studies, patients who discontinue therapy are not at an increased risk of clinical progression provided that ART is reinitiated before CD4+ counts fall below 200 cells/mm. The aim of this study was to identify predictive markers for declines in CD4+ cell count to < 350/μL and to evaluate the long-term effects of CD4-guided antiretroviral treatment interruptions (TI)
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