Induction and maintenance therapy with intermittent interleukin-2 in HIV-1 infection

Abstract

Studies establishing that intermittent subcutaneous interleukin-2 (IL-2) therapy can lead to substantial CD4 cell increases in many HIV-infected patients have generally been of limited duration. We studied 77 patients participating in active longitudinal studies of subcutaneous IL-2 therapy at our center in order to determine the long-term feasibility of this approach. Following initial induction, patients in each trial were eligible to receive intermittent 5-day cycles of subcutaneous IL-2 treatment at individualized doses and frequencies capable of maintaining CD4 counts at postinduction levels. The mean duration of study participation to date is 5.9 years (range, 1.0-9.3 years). Mean baseline CD4 cell count and CD4 percent values of 0.521 ؋ 10 9 /L (521 cells/ L) and 27% have risen to 1.005 ؋ 10 9 /L (1005 cells/L) and 38%, respectively, at 90 months. The mean number of subcutaneous IL-2 cycles required to achieve and maintain these increases was 10 cycles (range, 3-29 cycles), and the current mean interval of cycling required to maintain these elevations is 39 months (median, 35 months; range, 2-91 months). We conclude that subcutaneous IL-2 therapy is capable of maintaining CD4 cell increases for an extended period using a remarkably low frequency of intermittent cycling. These observations may contribute to patients' acceptance of subcutaneous IL-2 as a favorable long-term treatment strategy. (Blood. 2004;103:3282-3286)

IL-2 Regulates Perforin and Granzyme Gene Expression in CD8+ T Cells Independently of Its Effects on Survival and Proliferation

“…This is particularly pertinent to studies of IL-2 treatment in HIV infection. Because IL-2 is generally used to reconstitute the immune system, most reports from clinical trials in HIV infection focus on its effect on CD4 ϩ T cell numbers (56,57). However, CD8…”

IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates

“…IL-2 was the first of the T cell "growth factors" to be discovered, and as a result, it has been extensively evaluated as a therapeutic approach to T cell reconstitution (16). Significantly, while long-term, intermittent low-dose IL-2 therapy in HIVinfected individuals has been shown to be efficacious in increasing CD4 + T cell numbers in peripheral blood (36)(37)(38), the CD4 + T cells increased by these regimens are predominantly naive, and to a lesser extent T CM , in phenotype (36). The effect of such longterm IL-2 therapy on tissue CD4 + T EM cell populations has not been reported, but efficient repletion of this compartment would not be predicted on the basis of this pattern of activity.…”

Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2

“…[7][8][9][10][11] Moreover, CD4 ϩ T-cell expansions can be lastingly maintained by low frequency IL-2 administration. 12 Expanded cells comprise naive and memory CD4 ϩ T cells, as well as foxP3 positive, but poorly suppressive, CD4 ϩ CD25 ϩ T cells. 13 In the present study we investigated the effect of IL-2 therapy in combination with effective ART on the NKT cell compartment in primary HIV-1 infection.…”