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During HAART Interruption Interleukin-2 Was Ineffective in Maintaining Baseline CD4 T Cell Counts in IL-2-experienced Recipients: Results of a Randomized, Controlled Trial
Brian Porter*1, K Anthony2, J Shen1, B Hahn1, B Blackwelder1, C Lane1, J Kovacs1, R Davey1, and I Sereti1
1NIH, Bethesda, MD, US and 2Univ of Pennsylvania Hlth System, Philadelphia, US
Background: Intermittent cycling of subcutaneous
interleukin (IL) -2 leads to sustained increases in peripheral CD4 T cells in
HIV+ patients on HAART. However, IL-2 as HAART-sparing therapy has
been only partially investigated.
Methods: The ICARUS study was a randomized,
controlled, phase II non-inferiority trial of 40 IL-2-experienced (≥3
past cycles) adult HIV-1 infected patients with baseline CD4 counts ≥500 clearance
volume (cl)/µL. Following a 5-day cycle of IL-2 upon enrollment, participants
were randomized 2:1 to HAART treatment interruption or continuous therapy for 6
months, with monthly CD4 and viral load monitoring and an extensive metabolic
assessment at baseline and month 6. Participants in the continuous therapy arm
could undergo treatment interruption at month 6, and follow-up continued for a
total of 12 months. Additional IL-2 cycles (with 10 days of peri-cycle HAART
during treatment interruption) were given up to every 8 weeks for consecutive
CD4 counts <90% of baseline. Treatment success was defined as having a CD4
count ≥90% of baseline at month 6. Non-inferiority was defined as a
difference in success proportions (treatment interruption/continuous therapy)
with a lower 95% confidence limit ≥20%. Mann-Whitney and Fisher’s exact
tests were used to compare group medians and proportions.
Results: Both groups were comparable at baseline (treatment
interruption: 96% male, 96% white, 46 years of age; continuous therapy: 100%
male, 92% white, 45 years of age). At month 6 CD4 T cell count and viral load significantly
differed (see the table), as did treatment success rates (percentage difference
= –40.5%; 95%CI –60.9%, –10.2%). Metabolic differences are shown below. No
significant differences were seen in body mass index, percentage of body fat,
anthropometric measurements, CT scan fat measures, component lipids, glucose
tolerance, thyroid function, or hepatobiliary tests. During treatment
interruption, we observed in separate patients an acute retroviral syndrome, a
case of secondary syphilis, and, after month 12, a recurrence of Kaposi’s
sarcoma and a new diagnosis of non-Hodgkin’s lymphoma.
Conclusions: Treatment interruption combined with
intermittent IL-2 is inferior to HAART plus IL-2 in maintaining baseline CD4 T
cell counts in IL-2-experienced recipients.
|
|
Treatment Interruption (n = 27)
|
Continuous Therapy
(n = 13)
|
|
Baseline
|
Month 6
|
Baseline
|
Month 6
|
|
CD4*
(range)
|
947 cl/µL
(538 to 1390)
|
866 cl/µL
(445 to 1698)
|
947 cl/µL
(639 to 1326)
|
1246 cl/µL
(517 to 2253)
|
|
HIV VL*
|
<50 copies/mL
|
39,389 copies/mL
|
<50c/ml
|
<50 copies/mL
|
|
Tx Success**
|
51.9%, CD4 change –93 cl/µL
|
92.3%, CD4 change 396
cl/µL
|
|
HgA1c*
|
4.9%
|
5.4%
|
4.8%
|
5.0%
|
|
Cholesterol**
|
209 mg/dL
|
161 mg/dL
|
216 mg/dL
|
190 mg/dL
|
|
ApoA**
|
107 mg/dL
|
98.5 mg/dL
|
112.5 mg/dL
|
111 mg/dL
|
*p
≤0.001 treatment interruption vs continuous
therapy at month 6
**p
<0.05 treatment interruption vs continuous
therapy at month 6;
Tx = treatment
|
