The effect of continuous versus pericycle antiretroviral therapy on IL-2 responsiveness

Background: Intermittent administration of interleukin-2 (IL-2) to human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is capable of inducing significant increases in CD4 T cell counts as a result of increased T cell survival and decreased cell turnover. However, its role in the setting of ART interruptions (STI) is less well characterized. We sought to compare the effect of continuous (C) versus intermittent (P) ART on CD4 responses in patients undergoing IL-2 therapy. Methods: CD4 cell responses were compared in 25 patients who underwent IL-2 therapy during periods of continuous ART (n = 90 cycles) as well as during STI (n = 45 cycles). During STI, patients resumed ART for only 10 days surrounding each IL-2 cycle. Results: C cycles resulted in a significantly greater CD4 gain than P cycles (Delta 156 cells/mu L, 95% CI = 68-243). In multivariate analyses, baseline CD4/CD25 expression and treatment arm remained strong predictors of CD4 gain while CD8/CD38(+), CD8/DR+, and CD4 Ki67(+) phenotype were not predictive. Conclusions: Continuous ART was associated with a statistically significantly greater CD4 cell response to IL-2 therapy than was intermittent ART. These observations may have important implications for the appropriate integration of IL-2 therapy into STI strategies.

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