Different immunologic profiles characterize HIV infection in highly active antiretroviral therapy-treated and antiretroviral-naïve patients with undetectable viraemia. The Master Group.
BACKGROUND
Suppression of human immunodeficiency virus (HIV) replication can be obtained in chronically infected individuals by highly active antiretroviral therapy (HAART) and can also be observed in antiretroviral-naïve patients. The immunological correlates of these two situations were examined.


METHODS
Cross-sectional study involving 32 HIV-infected patients with undetectable HIV plasma viraemia (< 500 copies/ml) and either antiretroviral-naive (n = 14) or undergoing HAART therapy with two nucleoside reverse transcriptase inhibitors (NRTI) plus one (n = 13) or two (n = 5) protease inhibitors (PI). CD4 counts, disease duration, and CDC clinical stage were comparable between the two groups of individuals. Immune parameters (antigen- and mitogen-stimulated proliferation and cytokine production; cytokine mRNA; beta chemokine production; HIV coreceptors mRNA) were analysed in all patients.


RESULTS
Results showed immune profiles to be profoundly different in antiretroviral-naive in comparison with HAART-treated patients. Thus: (1) T-cell proliferation to HIV-specific and HIV-unrelated antigens is potent in antiretroviral-naive but suppressed in HAART-treated individuals; (2) interleukin-(IL)2, IL-12 and interferon gamma (IFNgamma) production is robust in naive patients; and (3) a high CCR5/low CXCR4 pattern of HIV coreceptors-specific mRNA is observed in naive but not in HAART-treated patients. In contrast with these observations, no clear differences were detected when beta chemokine production by either peripheral blood mononuclear cells or purified CD8+ T-cells was analysed. Results from HAART-treated patients undergoing therapy with one PI and two NRTI or two PI and two NRTI were in very close agreement.


CONCLUSIONS
These data suggest that control over HIV replication can be independently achieved by pharmacological or immunologic means. HAART is associated with weaker HIV-specific and -non-specific immune responses.
Clerici
M
M
Cattedra di Immunologia, Universitá degli Studi di Milano, Padiglione L.I.T.A., Ospedale L. Sacco, Italy. mago@mailserver.unimi.it
Seminari
E
E
Suter
F
F
Castelli
F
F
Pan
A
A
Biasin
M
M
Colombo
F
F
Trabattoni
D
D
Maggiolo
F
F
Carosi
G
G
Maserati
R
R
D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D012333:RNA, Messenger; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018894:Reverse Transcriptase Inhibitors; D018664:Interleukin-12; D007371:Interferon-gamma