The Virologic, Immunologic, and Clinical Effects of Interleukin 2 With Potent Antiretroviral Therapy in Patients With Moderately Advanced Human Immunodeficiency Virus Infection

Abstract

Background: Interleukin 2 (IL-2) administration increases CD4 counts in persons with higher counts. This study investigated persons with moderately advanced human immunodeficiency virus infection receiving highly active antiretroviral therapy (HAART). Methods: Two hundred four patients with CD4 T-cell counts from 50/µL to 350/µL who were treatment naive or had been treated only with reverse transcriptase inhibitors began a specified protease inhibitor HAART regimen. Virologic responders (Յ5000 copies/mL) at 12 weeks were randomized to open-label continuousinfusion IL-2 (IV IL-2), subcutaneous IL-2 (SC IL-2), or HAART alone. Thirty were not randomized and 15 enrolled in a substudy, leaving 159 for analysis. Subjects continued HAART alone for 72 weeks (n = 52) or with IV IL-2 (n = 53) or SC IL-2 (n = 54) for 5 days every 8 weeks. The IV IL-2 subjects could switch to SC IL-2 if their CD4 T-cell count increased by 100/µL or by 25%. Results: Patients receiving IV or SC IL-2 had greater increases in CD4 cell counts. At week 84, median increases were 459/µL, 312/µL, and 102/µL. Increases of greater than 50% at week 60 (primary end point) were achieved in 39 patients (81%) and 32 (67%) in the IV and SC IL-2 arms, respectively, compared with 13 (29%) in the HAART arm (PϽ.001 for both). Treatment with IL-2 did not increase plasma human immunodeficiency virus RNA levels. There were fewer new AIDS-defining events in the IV (P=.006) and SC (P=.03) IL-2 groups than in the HAART group (0, 1, and 7, respectively). Drug-related adverse events were more frequent with IL-2 treatment. Conclusion: Addition of IL-2 to HAART can significantly expand CD4 T-cell counts in moderately advanced human immunodeficiency virus infection, without loss of virologic control.

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).…”

“…+ lymphopenia [21][22][23][24]. However, our patient did not have clinical features consistent with any of these syndromes, a personal or family history of malignancy or a karyotypical analysis consistent with chromosomal instability.…”

“…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.…”

Quality of Life in a Clinical Trial of Highly Active Antiretroviral Therapy Alone or With Intravenous or Subcutaneous Interleukin-2 Administration

“…Median CD4 + cell count changes at the end of the study (week 84), were +102, +312, and +459 3 10 6 cells/L, respectively, for the HAART only, HAART plus subcutaneous IL-2, and HAART plus intravenous IL-2 groups (P = 0.001). 18 Interestingly, the subcutaneous IL-2 group had the best HRQOL scores overall, but the intravenous group had the best immunologic measures of the 3 treatment groups. HRQOL scores in the intravenous IL-2 group may have been affected by issues of inconvenience and time required for treatment, which were not specifically asked about on our questionnaires.…”

Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts during HAART interruption: a randomized controlled trial

“…Several phase II studies have documented IL-2 dose-dependent expansions of CD4 T cells, with increases in naïve and memory subsets due to improved survival and decreased immune activation when administered with HAART [13, 18, 24, 25, 42]. The immune restoration conferred by HAART alone is incomplete, however, despite reductions in CD4 T cell activation, turnover, and lymphopenia [43–46].…”