Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group.
BACKGROUND
Intermittent interleukin-2 therapy for HIV-1 by continuous intravenous infusion leads to sustained increase of CD4 T cells. This method of administration is, however, inconvenient and has limiting toxic effects. We did a randomised study to compare safety and efficacy of antiviral treatment alone or combined with various interleukin-2 regimens in HIV-1-infected patients.


METHODS
94 symptom-free patients, naïve to antiretroviral treatment, with CD4-T-cell counts of 250-550 cells/microL at baseline were randomly assigned zidovudine and didanosine alone (n=26) or combined with interleukin-2 administered intravenously (12 million IU/day, n=22) or subcutaneously (3 million IU/m2 twice daily, n=24) for 5 days, or were given polyethylene-glycol-modified (PEG) interleukin-2 (2 million IU/m2 intravenous bolus, n=22) administered every 2 months from week 2 to week 50 (seven cycles). Safety and immunological and virological results were monitored until week 56.


RESULTS
CD4-T-cell count increased to higher than baseline by a mean of 564 cells/microL (subcutaneous group), 676 cells/microL (intravenous group), 105 cells/microL (PEG group), and 55 cells/microL (antiretroviral-therapy group, p=0.0001). 68% and 77% of patients in the subcutaneous and intravenous groups, respectively, achieved an 80% increase of CD4 T cells (p<0.001). In these two groups, 50% of patients restored a CD4/CD8-T-cell ratio of more than 1. The groups did not differ significantly for changes in plasma HIV-1 RNA loads throughout the study. The duration of common side-effects of interleukin-2 was shorter in the subcutaneous group, which enabled outpatient treatment. Naïve and memory CD4 T cells, CD28 expression on CD4 and CD8 T cells, and restoration of in-vitro proliferative response to mitogens and recall antigens increased in the intravenous and subcutaneous groups.


CONCLUSIONS
Subcutaneous interleukin-2 is a convenient regimen that, as well as intravenous therapy, improves immunological function in HIV-1-infected patients receiving two nucleosides. Larger studies are needed to show whether immunological improvements translate into clinical benefit.
Levy
Y
Y
Unité d'Immunologie clinique, Hôpital Henri Mondor, Creteil, France. yves.levy@hmn.ap-hop-paris.fr
Capitant
C
C
Houhou
S
S
Carriere
I
I
Viard
J P
JP
Goujard
C
C
Gastaut
J A
JA
Oksenhendler
E
E
Boumsell
L
L
Gomard
E
E
Rabian
C
C
Weiss
L
L
Guillet
J G
JG
Delfraissy
J F
JF
Aboulker
J P
JP
Seligmann
M
M
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D007376:Interleukin-2; D015215:Zidovudine; D016049:Didanosine