Efficacy of recombinant interleukin-2 (rIL-2) in patients with advanced HIV-1 infection and blunted immune response to HAART.
OBJECTIVE
The efficacy of recombinant interleukin-2 (rIL-2) was assessed in HIV-infected patients with advanced immune suppression and a discordant immune response to highly active antiretroviral therapy (HAART). The primary endpoint was median change in CD4+ T-cell counts at the end of treatment as compared to baseline. Secondary endpoints were safety and changes in the various T-cell subpopulations.


METHODS
In a prospective cohort study, 19 patients with HIV-RNA < 50 copies/mL and < 200 CD4+ T cells/mm3 without a significant increase in the previous 12 months were scheduled to receive 6 cycles of 4.5 x 10(6) IU subcutaneous rIL-2 daily for 5 consecutive days, every 4 weeks.


RESULTS
Median age was 43 years, and 64% had a previous AIDS-defining event. Median nadir and baseline CD4+ cell counts were 36 and 99 cells/mm3, respectively. Three patients discontinued treatment and one experienced grade 4 side effects. CD4+ T-cell counts increased to 147 cells/mm3 (range, 24-285) at 1 month following completion of treatment (P = 0.002), and 180 cells/mm3 (range, 38-280) at 18 months (P < 0.001). This improvement was associated with a significant decrease in expression rates of the activation markers, HLA-DR and CD38.


CONCLUSIONS
Our results suggest that in patients with advanced HIV-infection showing a blunted immune response to HAART, rIL-2 might increase the pool of CD4+ T-cells by down-regulating the status of immune activation.
Crespo
Manuel
M
Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain. mcrespo@vhebron.net
Caragol
Isabel
I
Falcó
Vicenç
V
Ribera
Esteban
E
Urban
Susana
S
Pahissa
Albert
A
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005334:Fever / Q000139:chemically induced; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008231:Lymphopenia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D019562:Viral Load
D016207:Cytokines; D007155:Immunologic Factors; D007376:Interleukin-2; D011994:Recombinant Proteins