Using IL-2 With Low CD4s.

Christine Katlama reported on study ANSR 082 which is a randomized comparitive open-label study in 19 centers in France of IL-2 in patients with CD4 below 200 despite effective HAART. Patients were included in this study if they had CD4 count between 50-200, if their viral load was below 1000 copies/ml, and on stable HAART for a minimum of 6 months.

Patients were randomized to IL-2 +HAART or no IL-2. The IL-2 was given sub-cutaneous 4.5 MIU bid in 4 cycles of 5 days every 6 weeks up to week 24. After 24 weeks IL-2 was given s.c. 9 MIU qd for 5 days every 8 weeks up to week 80. After week 24, IL-2 was offered to initial control group and if they still fit the inclusion criteria. 72 patients were randomized and 70 were evaluated. 31 patients in the IL-2 group completed the 24 weeks on IL-2. Three of 34 patients discontinued: 1 for adverse event, 1 wanted to stop, and 1 for progression to KS. Five patients reduced their dose.

After 24 weeks, 89% in the control group started IL-2 and 82% in IL-2 group continued with IL-2. 55% of patients in both groups had a prior AIDS defining event. They were all on mean duration of HAART for about 18 months. At initiation of HAART CD4 was about 65. After 6 months on HAART CD4s were 113 in IL-2 group and 89 in control group. At study entry CD4s were 149 in IL-2 group (n=34) and 138 in control group (n=36). The % with below 100 CD4s was 15% in the IL-2 group and 22% in the control group.

76% in the IL-2 group and 89% in the control group had below 200 copies/ml. 18% in the IL-2 group and 8% in the control group had 200-500 copies/ml. And, 6% in the IL-2 group and 3% in the control group had 500-1000 copies/ml.

Results.  At week 24 by ITT analysis, there was a highly significant difference between the two groups. The median CD4 count was 220 in the IL-2 group (range 101-394) and 158 (30-281) in the control group. The median increase was 65 (12-228) in the IL-2 group and 18 (-60 to 107) in the control group. The % of patients with CD4 increase of at least 50 was 73% in the 1L-2 group and 22% in the control group. The % with at least an 80 CD4 increase was 41% in the IL-2 group and 3% in the control group.

During the study 6 in the IL-2 group and 2 in control group had transient rise in viral load above 1000 copies/ml. Within 1 or 2 evaluation points the viral load returned to below 1000.

There was a significant increase in the proliferation activity against CMV with 58% in the IL-2 group who became positive (30% at baseline) compared to 21% (44% at baseline) in the control group. There was no significant difference between the 2 groups at baseline and week 24 using PPD, tetanus and p24 Ag. There was no activity at baseline and week 24 against p24.

There was a significant higher rise both in memory cells (44 in IL-2 group versus 1 in control group) and na´ve cells (27 IL-2 versus 5 in control). Nearly all patients experienced the expected IL-2 side effects: fever, fatigue, muscle pain, nausea, rhinitis, sweats, dry skin/mouth, rash, arthralgia, insomnia, headache. But there was only 1 discontinuation of IL-2 and 5 dose reductions. Over 90% experienced fever and fatigue.

Additional cycles of IL-2 may result in continued increases in CD4s.