Low‐Dose Prolonged Intermittent Interleukin‐2 Adjuvant Therapy: Results of a Randomized Trial among Human Immunodeficiency Virus–Positive Patients with Advanced Immune Impairment

Abstract

Twenty-two patients with CD4(+)cell counts <or=200 cells/microL after 12 months of stable highly active antiretroviral therapy (HAART; "immunologic nonresponders") were randomly assigned to receive subcutaneous low-dose prolonged intermittent interleukin (IL)-2 in addition to HAART (n=12) or to continue HAART alone (n=10). At 48 weeks of follow-up, no IL-2-related serious adverse events and no significant differences in plasma human immunodeficiency virus (HIV) RNA level were observed in the 2 groups. A higher incidence of HIV-related clinical events was observed among patients receiving HAART alone (3/10) than among subjects receiving HAART plus IL-2 (0/12). Significant increases in CD4(+), naive, and CD4(+)CD7(+) cells and plasma levels of IL-7 were observed in patients receiving IL-2 versus patients receiving HAART alone. A significant increase in cell turnover did not lead to a decrease in the frequency of T cell receptor excision circles, which remained stable. Rather, increased numbers of T cell receptor excision circles per microliter of blood were observed (not statistically significant). Thus, adjuvant IL-2 therapy in immunologic nonresponders resulted in a clinical benefit, suggesting that the quantitative cell recovery involves functionally competent immune cells.

Detrimental Immunologic Effects of Preoperative Chemoradiotherapy in Advanced Rectal Cancer

“…As far as the clinical relevance of these findings is concerned it should be pointed out that studies on adjuvant immune therapy in patients with HIV infection usually include patients with CD4ϩ cell counts below 200 cells/l, because these patients are considered advanced immune impaired. 29 In patients after preoperative chemoradiotherapy we observed CD4ϩ cell counts as low as 200 cells/l on Days 1 and 2 after surgery. Therefore, it seems that these patients may also be considered advanced immune impaired.…”

Safety and efficacy of treatment using interleukin-2 in a patient with idiopathic CD4+ lymphopenia andMycobacterium avium-intracellulare

“…Based on the Wilhem et al case report, we selected IL-2 at 600 000 IU/day as this was the lowest, well-tolerated dose that produced a significant and undelayed increase in CD4 + cell counts [14].We increased the dose as tolerated to achieve CD4 + counts greater than 300 cells/mm 3 , but unlike other case reports we titrated based on a three doses per week regimen, because of the patient's preference. The weekly 11 million IU (divided into three doses) our patient received exceeded the 7 million IU weekly (1 million daily) that Wilhem et al reported and was fewer than the intermittent doses used in HIV trials [14,[24][25][26][27] ( Table 1).…”

“…Interestingly, our patient appeared to have a prolonged immunological laboratory response to IL-2 therapy 6 months following IL-2 discontinuation; however, this effect appears to have diminished in the most recent laboratory results. The reason for this observation may include the differing dosage amount and scheduling of our patient's IL-2 regimen compared with other ICL case reports and HIV studies [12][13][14][15][24][25][26][27]. Continued out-patient monitoring will be required to elucidate more fully the durability of the clinical and immunological response.…”

Immunotherapy and Therapeutic antibodies

“…Highly active antiretroviral therapy (HAART) induces a substantial control of HIV viral replication [53], but it allows for only a partial immune reconstitution, thus prompting the rationale for the adjuvant use of immunomodulants. Based on its in vitro action as a major T cell growth factor, interleukin (IL)-2 has now been extensively investigated for its potential to correct the HIV-driven immune deficiencies, possibly translating into immunological control over HIV infection.…”