The results of the primary analysis of the study have been recently published. 
In summary, three cycles of interleukin-2 given during the first 18 weeks of the study, delayed the initial decay of CD4 T cells after TI, but this benefit was lost by 72 weeks. Twenty-one of the study subjects were on a protease inhibitor based regimen.
Baseline and week 16 changes from baseline in fasting total cholesterol, triglycerides, HDL cholesterol and non-HDL cholesterol, fasting glucose and insulin were comparable between the study arms (). Although there were statistically marginally significant differences observed with respect to week 16 cholesterol and non HDL cholesterol (p
0.04 and p
0.03, not corrected for multiple comparisons), within each arm there were no significant changes from baseline. Because of these results the metabolic parameters from subjects in both arms after interruption were combined.
Summary of changes in lipid and glucose parameters during Step 1 of the trial, when participants were receiving ART with or without IL2.
The baseline values for subsequent analysis are the ones immediately before treatment interruption. After the discontinuation of ART there was a rapid decrease of the concentrations of total cholesterol. By week 8 of TI, levels of total cholesterol (TC) decreased (median(Q1, Q3)
−0.73 (−1.19, −0.18) mmol/L, p<0.0001) as well as triglycerides (−0.40 (−0.84, 0.07) mmol/L, p
0.005). LDL and HDL cholesterol also decreased (−0.36(−0.73,−0.03)mmol/L, p
0.0007 and −0.05(−0.26,0.03), p
0.0033, respectively) (). These decreases persisted for the duration of the follow up. All of these changes were evident before the return of detectable HIV plasma RNA, defined by HIV-1 RNA >500 copies/mL. Rebounding HIV-1 RNA values >500 copies/mL were identified at 2 weeks in 20 of 45, after 4 weeks in 35 of 45, and for 45 of 45 by week 8 of treatment interruption. This suggests that lipid changes were mediated directly by the discontinuation of ART and not by HIV replication itself. After 48 weeks off therapy there was a continuing decrease in HDL levels and a continuing increase in triglyceride levels.
Glucose and Lipid Metabolism During Prolonged TI (median % change from baseline and IQR).
The total cholesterol to HDL cholesterol ratio decreased slightly during the first 4 weeks (−0.5,IQR −1.2–0.06, p
0.001) after TI but returned to baseline by week 8 (−0.09 (IQR −1.2, 0.5), p
0.2) and remained unchanged afterwards due to the marked decreases in HDL cholesterol ().
Total cholesterol to HDL ratio changes overtime after treatment interruption (median change and IQR).
After interruption the percentage of individuals with HDL cholesterol less than 40 mg/mL (1.04 mmol/L) went from 53% before discontinuation to 76% after 48 weeks. After the discontinuation of ART there were no significant changes in either the fasting glucose or insulin levels.
During Step 1 (continuous ART), there was no significant difference within the arms in the change from baseline in the percentage of CD8+ T-cells expressing activation markers (HLA-DR and CD38). The median baseline absolute number of CD8+/HLA DR+ cells were 220 in the IL-2 arm and 204 cells per mm3
in the no-IL2 arm, at the end of step 1 they were 267 and 231 per mm3
0.55). There was no significant difference within the arms in the change from baseline in the percentage of CD8+ T-cells expressing activation markers (HLA-DR and CD38). Nevertheless, during Step 1 subjects in the IL-2 group (median change −1%, IQR: −3 to 0%) tended to experience a decrease in the percent of activated CD8+ T-cells while those not receiving IL-2 tended to experience an increase (median change 1%, IQR: −1 to 5%; p
0.03, Wilcoxon test for the difference between arms).
As expected, after the discontinuation of treatment there was a significant increase in cellular and soluble activation markers in all participants. The increase in CD8+ T-cell activation was faster among individuals that received ART alone during Step 1. These patients experienced a significant increase in activation at week 2 of Step 2 (median increase 3%, vs 0% p
0.01), while those not receiving IL-2 did not experience a significant increase in activation until week 4 (median increase 20%, p
0.0002). By eight weeks after ART discontinuation the median increase in activated CD8+ cells was similar between groups (median increase 32% and 42% for IL-2 and non-IL-2 recipients, p
0.17). After 8 weeks of TI the percentage of activated CD8 cells in the whole group (HLA-DR+ and CD38+ positive) had increased a median of 34% (IQR 13–43%, Wilcoxon signed rank p<0.0001). The levels of TNF receptor alfa II increased approximately by 30% after 24 weeks after the discontinuation of ART (1089 ng/L (−189, 1655), p
There were no significant correlations between the changes in lipid or glucose parameters and the changes in immune activation markers or viral markers during the first weeks of follow up (data not shown).