Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial

Y Levy, C Capitant, S Houhou, I Carriere, JP Viard… - The Lancet, 1999 - thelancet.com
Y Levy, C Capitant, S Houhou, I Carriere, JP Viard, C Goujard, JA Gastaut, E Oksenhendler…
The Lancet, 1999thelancet.com
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, naļve to antiretroviral treatment,
with CD4-T-cell counts of 250–550 cells/μL at baseline were randomly assigned zidovudine …
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, naļve to antiretroviral treatment, with CD4-T-cell counts of 250–550 cells/μL 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.
Findings
CD4-T-cell count increased to higher than baseline by a mean of 564 cells/μL (subcutaneous group), 676 cells/μL (intravenous group), 105 cells/μL (PEG group), and 55 cells/μL (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. Naļve 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.
Interpretation
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.
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