Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART.
OBJECTIVE
Inadequate CD4 cell count recovery despite full HIV RNA control occurs in 30% of HAART-treated HIV-infected patients. A better understanding of the relationship between T-cell dynamics and the HIV intracellular reservoir in HIV-infected patients failing to recover CD4 cell count following long-term HAART, is required.


METHODS
In a cross-sectional study T-cell turnover and homeostatic parameters featuring discordant responses were investigated in 27 immunologic non-responders (INR; CD4 count, < or = 200 cells/microl; HIV RNA, < or = 50 copies/ml), 15 virological non-responders (VNR; CD4 count, > or = 350 cells/microl; HIV RNA, > or = 10 000) and 22 full responders (FR; CD4 count, > or = 500 cells/microl; HIV RNA, < or = 50 copies/ml).


RESULTS
INR displayed significantly higher activated CD38CD8 than FR (P < 0.05) and was comparable to VNR (P > 0.05). As compared with VNR and FR, INR displayed the highest level of proliferating Ki67CD4 and apoptotic CD4 cells (P < 0.05). VNR presented lower proliferation and apoptosis than FR and INR. INR displayed the lowest levels of naive T cells (P < 0.05) and a predominant memory pattern. Despite the memory/activated/apoptotic phenotype, INR showed a statistically non-significant reduction in T-cell receptor excision circles (TREC) compared to FR (P > 0.05), and substantially heightened interleukin (IL)-7 (P < 0.05), while VNR showed higher naive T-cell counts and TREC. Moreover, the reservoir of infected CD4 cells was increased in INR, with a trend toward highest intracellular HIV DNA within total, naive and memory CD4 cells.


CONCLUSIONS
The lack of CD4 cell count recovery in INR seems to reflect a highly activated apoptotic T-cell compartment, with elevated IL-7 and thymic impairment. High levels of intracellular HIV-DNA in INR could be strictly involved in the lack of T-cell reconstitution. Immune correlates of an ultimate direction of the response to HAART, could be exploited in clinical practice for the most effective management of discordant patients, to amend immune imbalances and to improve clinical outcome.
Marchetti
Giulia
G
Department of Clinical Sciences, Chair of Infectious Diseases and Tropical Medicine, Luigi Sacco Hospital, University of Milan, via G.B. Grassi 74, 20157 Milan, Italy. giulia.marchetti@unimi.it
Gori
Andrea
A
Casabianca
Anna
A
Magnani
Mauro
M
Franzetti
Fabio
F
Clerici
Mario
M
Perno
Carlo-Federico
CF
Monforte
Antonella d'Arminio
Ad
Galli
Massimo
M
Meroni
Luca
L
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000097:blood; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D013950:Thymus Gland / Q000276:immunology
D004279:DNA, Viral; D015851:Interleukin-7; D019394:Ki-67 Antigen