Seventh International Congress on Drug Therapy in HIV Infection Glasgow, UK - 14-17 November 2004

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL8.1

Jens D. Lundgren
Copenhagen HIV Programme, Hvidovre University Hospital, Hvidovre, Denmark

PURPOSE OF PRESENTATION: Provide an update on the current research efforts directed towards defining the potential clinical utility of interleukin 2 (IL-2) in slowing the progression of HIV-1 infection.

SUMMARY OF RESULTS: An extensive phase II database has established that intermittent 5 day cycles of IL-2 are capable of increasing circulating levels of CD4 T-lymphocytes in many patients. This effect is due primarily to proliferation of the peripheral pool of CD4 cells and to a subsequent increase in the survival time of the expanded CD4 population. The latter effect is most pronounced after several cycles of IL-2 induction, and often allows for extended periods of time (several years) to elapse between additional cycles of IL-2 required to maintain the CD4 response. Cellular mechanisms of these effects will be presented.

The benefit of IL-2 on CD4 cell numbers has been described in patients both on incompletely or fully suppressive antiretroviral therapy (ART) regimens as well as in ART-naïve patients. Factors associated with better responses to IL-2 include higher baseline CD4 counts, no prior severe immunodeficiency, shorter exposure to ART, younger age, black race, and a low level of ongoing HIV replication.

Constitutional symptoms are the most frequently observed adverse effects during IL-2 therapy. Patients vary markedly in their susceptibility to these treatment-limiting toxicities. Prophylactic use of combinations of paracetamol and NSAID at the time of IL-2 cycle initiation appear to reduce the severity of these adverse effects. Other types of adverse effects are observed less frequently and will be discussed.

Two ongoing, investigator-driven, fully enrolled (+6,000) phase III trials are exploring whether IL-2 can reduce the risk of HIV-related clinical disease progression. The enrolment criterion in the ESPRIT trial was a CD4 count > 300/µL, whereas the SILCAAT study enrolled more advanced patients with CD4 counts below this limit. Key to the scientific success of both trials will be the continued use of IL-2 as needed in order to maintain the difference in CD4 count numbers between the two arms of the study, to keep the lost-to-follow-up rate low, and to ensure that all clinical events are captured accurately during follow-up.

CONCLUSIONS: Evidence generated in the last 20 years provides a substantive database to suggest that the CD4 cells induced by IL-2 may reduce the risk of progression of HIV-related clinical disease. However, only the ongoing phase III trials are capable of addressing this question definitively and must be completed before IL-2 should be used in routine care. While these clinical endpoint trials are underway, exploration of additional potential therapeutic roles for IL-2, such as providing the backbone of ART-sparing strategies, should also be undertaken in patients at various stages of their disease.

SESSION 8: IMMUNOLOGY, IMMUNE-BASED THERAPIES AND VACCINES

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