JAC Advance Access originally published online on June 27, 2008
Journal of Antimicrobial Chemotherapy 2008 62(3):583-586; doi:10.1093/jac/dkn238
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Original research |
Long-term clinical and surrogate marker effects of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients
1 Department of Infectious Diseases, Vivantes Auguste Viktoria Klinikum, Rubensstr. 125, 12159 Berlin, Germany 2 HIV Clinical Research, Royal Free Hospital, London, UK 3 University of Minnesota, Minneapolis, MN, USA 4 Elton John Centre, Royal Sussex Hospital, University of Brighton, Brighton, UK 5 Department of HIV Medicine, Chelsea and Westminster Hospital, London, UK 6 National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
Received 6 March 2008; returned 8 April 2008; revised 21 May 2008; accepted 22 May 2008
* Corresponding author. Tel: +49-30-78717533; Fax: +49-30-78715732; E-mail: christian.herzmann{at}web.de
Objectives: Subcutaneous administration of interleukin-2 (IL-2) has been shown to increase CD4 counts in HIV-infected patients. It remains unclear whether this effect is associated with a clinical benefit.
Patients and methods: We conducted a long-term follow-up in the cohort of the UK-Vanguard study in which three groups of 12 antiretroviral-naive subjects with CD4 cell counts >350 cells/mm3 received no treatment or IL-2 at either 4.5 or 7.5 MIU twice daily in 5 day cycles, respectively.
Results: Mean follow-up was 376 weeks. IL-2 therapy was associated with a higher area under the curve of CD4 cell count change from baseline at week 48 but not thereafter. HIV-RNA levels were unaffected. Highly active antiretroviral therapy (HAART) was initiated after a mean of 172, 175 and 152 weeks in the control group, low-dose and high-dose IL-2 treatment group, respectively, a statistically non-significant difference. There was a tendency to start HAART soon after discontinuation of IL-2 therapy which may have been triggered by the steep decay of CD4 counts. There were two serious adverse events in the control group, seven in the low-dose IL-2 group and eight in the high-dose IL-2 group. No pattern of disease was detected, making an association with IL-2 therapy unlikely.
Conclusions: We could detect neither a benefit of IL-2 therapy after week 48 nor delayed initiation of HAART. This is currently the longest follow-up data comparing IL-2 therapy with no therapy in antiretroviral-naive HIV-infected patients and does not show a persistent benefit of the intervention.
Keywords: immunomodulation , CD4 cell count , HIV viral load , UK Vanguard , long-term follow-up