Evaluating the Clinical Benefit of Interleukin-2 Plus Antiretroviral Therapy: Is Raising CD4+ Cell Counts Sufficient?

Abstract

Since early in the AIDS epidemic, CD4 counts were recognized as the single best indicator of immunologic status in patients with HIV disease and are still used to define a patient’s risk of AIDS-related and other serious diseases. Thus, treatments that help boost CD4 counts beyond levels achieved by antiretroviral therapy (ART) alone may lead to improved health outcomes in patients with HIV disease. This could be of particular benefit in patients who fail to achieve significant increases in CD4 counts on ART despite achieving appropriate virologic control with low or undetectable HIV viral loads. Interleukin (IL)-2 is a potent inducer of CD4 cells, and subcutaneous recombinant IL-2 combined with ART results in significant sustained increases in CD4 counts in HIVinfected patients compared with ART alone. However, it is unclear if these increases in CD4 counts would translate into observed clinical benefit in HIV-infected individuals. In addition, there are many toxicities, some potentially fatal, associated with IL-2 use, which may outweigh any clinical benefit of this treatment. The Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients With Low CD4 Cell Counts Under Active Antiretroviral Therapy (SILCAAT) and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) were international multicenter studies designed to address whether there was any clinical benefit from the use of IL-2 with ART beyond the known increases in CD4 counts.