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/microL 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/microL, 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/microL.


RESULTS
After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4+ cell count to < 350/microL. Patients with a CD4+ nadir of < 200 cells/microL 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/microL.


CONCLUSIONS
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.
Seoane
Elena
E
Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain. meseoane.hdoc@salud.madrid.org
Resino
Salvador
S
Moreno
Santiago
S
de Quiros
Juan Carlos Lopez Bernaldo
JC
Moreno
Ana
A
Rubio
Rafael
R
Gonzalez-García
Juan
J
Arribas
José Ramón
JR
Pulido
Federico
F
Muñoz-Fernández
Ma Angeles
MA
D000328:Adult; D044966:Anti-Retroviral Agents / Q000097:blood* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D016207:Cytokines / Q000032:analysis; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007118:Immunoassay; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D013030:Spain; D016896:Treatment Outcome; D019562:Viral Load
D044966:Anti-Retroviral Agents; D016207:Cytokines; D012367:RNA, Viral