Low-dose IL-2 reduces lymphocyte apoptosis and increases naive CD4 cells in HIV-1 patients treated with HAART.
During HIV disease an increased in vitro apoptosis of peripheral blood mononuclear cells has been demonstrated. This can be reversed in vitro by interleukin (IL)-2. Recent trials with highly active antiretroviral therapy (HAART) and IL-2 in HIV-1-infected patients showed promising immunological and clinical results. Here we investigated the effects of subcutaneous low-dose IL-2 administration in combination with HAART on in vitro apoptosis and the relationship between apoptosis, CD4(+) counts, and HIV replication. Twenty-two asymptomatic HIV patients were randomized for HAART (arm I) and HAART plus IL-2 (arm II). Spontaneous apoptosis was decreased in both arms after 28 weeks of therapy but the reduction was highly significant only in arm II (P = 0.05 vs P = 0.001). As the percentage of apoptosis decreased, there was a significantly higher increase of both CD4(+) and CD4(+) naive T cells in arm II vs arm I. HIV plasma viremia was reduced in all patients after therapy. Our data suggest that intermittent therapy with low-dose subcutaneous IL-2 in addition to HAART induces a positive immunomodulation in asymptomatic HIV-infected patients.
Pandolfi
F
F
Institute of Internal Medicine, Catholic University, Rome, Italy.
Pierdominici
M
M
Marziali
M
M
Livia Bernardi
M
M
Antonelli
G
G
Galati
V
V
D'Offizi
G
G
Aiuti
F
F
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage*; D018655:Lymphocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012190:Retroviridae / Q000187:drug effects; D019014:fas Receptor / Q000097:blood
D000998:Antiviral Agents; D007376:Interleukin-2; D012367:RNA, Viral; D019014:fas Receptor