Immunophenotype of HIV+ patients during CD4 cell-monitored treatment interruption: role of the IL-7/IL-7 receptor system.
OBJECTIVE
To investigate immunological changes during CD4-guided therapy interruption in HIV(+) patients who suspended HAART.


METHODS
Seventeen patients aged > 18 years, who had received HAART for at least 12 months, and had a pre-interruption CD4+ cell count > 500 cells/microl, interrupted treatment. Median nadir CD4(+) cell count was 288 cells/microl. HIV plasma viral load at discontinuation was < 50 or > 50 copies/ml. Criteria for restarting treatment were: a CD4(+) T-lymphocyte count < 350 cells/microl on two separate occasions, a clinical manifestation of AIDS, and the patient's desire to resume HAART. Eleven patients were still off therapy after 12 months (group A); according to the first criterion, six patients restarted therapy within 12 months (group B).


METHODS
Haematological, viro-immunological, cytofluorimetic and molecular assays were performed at baseline and every 2 months following standard methods. Statistical analysis was performed under Stata 7.0.


RESULTS
In the first 2 months of treatment interruption, a significant increase in viral load and CD8(+) lymphocyte activation occurred. Then such parameters decreased and remained stable. In all patients, a decrease in CD4(+) lymphocytes took place as well, that affected in a similar manner naive, central memory, effector memory and terminally differentiated cells. Group B always presented lower amounts of CD4(+) effector memory lymphocytes. The expression of CD127 was always higher in group A.


CONCLUSIONS
The loss of CD4(+) lymphocytes upon viral rebound is equal among naive and memory subsets. Patients with higher expression of CD127, who are likely to exert a better capacity to utilize endogenous interleukin-7 by T cells, could remain off therapy for longer periods.
Nemes
Elisa
E
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Lugli
Enrico
E
Nasi
Milena
M
Ferraresi
Roberta
R
Pinti
Marcello
M
Bugarini
Roberto
R
Borghi
Vanni
V
Prati
Francesca
F
Esposito
Roberto
R
Cossarizza
Andrea
A
Mussini
Cristina
C
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000097:blood*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019562:Viral Load
D019380:Anti-HIV Agents; D015415:Biomarkers; D015851:Interleukin-7; D020395:Receptors, Interleukin-7