Immunological and virological factors at baseline may predict response to structured therapy interruption in early stage chronic HIV-1 infection.
BACKGROUND
The objective was to analyse which baseline factors could predict a favourable outcome after structured therapy interruption (STI).


METHODS
Data of three Spanish pilot studies of STI in early stage chronic HIV-1-infected patients were analysed. A set of 37 variables at baseline was used. Plasma and tonsillar tissue viral load (VL), lymphocyte immunophenotyping and proliferative responses (LPR) to mitogens and specific antigens, and HIV-1 specific cytotoxic T lymphocyte responses were assessed at baseline. Response was defined as a VL set-point after 6 months off antiretroviral therapy after the last interruption of < 5000 copies/ml and 0.5 log(10) below baseline PVL before any antiretroviral therapy.


RESULTS
After STI, the 44 patients were classified as follows: 18 (41%) as responders, 26 (59%) as non-responders. In the univariate analysis patients who responded had a significantly lower baseline level of CD4CD38 (P = 0.0068) and naive CD4 T cells (P = 0.03), and a higher level of memory CD4 T cells (P = 0.03) and proliferative response to tetanus toxoid (TT) (P = 0.01) and HIV-1 p24 (P = 0.03) than non-responders. A model incorporating five qualitative variables transformed according to the median value (CD4CD38, CD4 naive and memory T cells and stimulation index to TT and HIV-1 p24) at baseline could classify 97% of patients correctly (P = 0.0001).


CONCLUSIONS
A level of memory CD4 T cells and proliferative response to recall antigens above the median may predict a good response to STI, suggesting that preserved memory response in CD4 T cells is important factor.
García
Felipe
F
Clinic Institute of Infections and Immunology, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain.
Plana
Montserrat
M
Mestre
Gabriel
G
Arnedo
Mireia
M
Gil
Cristina
C
Miró
José M
JM
Cruceta
Anna
A
Pumarola
Tomas
T
Gallart
Teresa
T
Gatell
José M
JM
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D010865:Pilot Projects; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors