AEGiS-08CROI: Prospective, randomized, controlled phase II study of highly active antiretroviral therapy (HAART) with continuous IV (CIV) or subcutaneous (SC) interleukin-2 (IL-2) in HIV-infected patients with CD4+ counts of 50-350 cells/mm

³: ACTG 328-final results at 84 weeks.

8th Conference on Retroviruses and Opportunistic Infections

Chicago, IL - February 4 - 8, 2001

Prospective, randomized, controlled phase II study of highly active antiretroviral therapy (HAART) with continuous IV (CIV) or subcutaneous (SC) interleukin-2 (IL-2) in HIV-infected patients with CD4+ counts of 50-350 cells/mm³: ACTG 328-final results at 84 weeks

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:48 (abstract no. 17)

R. Mitsuyasu¹, R. Pollard², R. Gelman³, and D. Weng³for the ACTG 328 Protocol Team
¹Univ. of California, Los Angeles; ²Univ. of Texas Med. Branch, Galveston; and ³SDAC, Harvard Univ., Boston, MA.

BACKGROUND: The objectives of this study were to ascertain the effects of IL-2 given by either CIV or SC routes added to HAART vs HAART alone on CD4 response, immune phenotype and function, antiviral effectiveness of HAART, tolerability and quality of life in patients (pts) with advanced HIV.

METHODS: 204 protease inhibitor-naïve pts (CD4 50-350) were treated with HAART alone (indinavir + 2 NRTIs) for 12 wks. If HIV RNA <5000 c/ml at wk 12, pts were randomized to HAART alone (n=52), HAART + CIV IL-2 at 9 MIU qd × 5d q8wks (n=54), or HAART + SC IL-2 at 7.5 MIU bid × 5d q8wks (n=55) for up to 84 wks. Pts on CIV could switch to SC IL-2 after 3 or 6 cycles if CD4 >25% and >100 cells above wk 12 baseline. IL-2 dose reduction was allowed in both IL-2 arms for toxicities or poor tolerance. Immunologic and virologic changes were assessed in the 3 arms every 8 wks. Primary endpoint at wk 60 was proportion of pts at wk 60 with >50% rise in CD4 count above wk 12 baseline. Pts were followed on randomized treatment arm to 84 wks.

RESULTS: 36/55 (65%) in SC and 39/54 (72%) in CIV completed at least 6 cycles of IL-2, with 40/54 (74%) crossing over to SC after 3 or 6 cycles. Average daily doses of IL-2 were 9.3 MIU/d in CIV and 9.8 MIU/d in SC arms. Changes from baseline to wk 84 were as shown in the table.

	HAART	H+CIV	H+SC
Median CD4 ct. week 12	283	247	237
Median CD4 ct. week 60	376	675	579
Median CD4 ct. week 84	396	800	614
Median CD4 ct. week 84 - week 12	121	480	302
% with <50% rise CD4 wk 12-84 (N=44 ea)	41	86*	77*
*p<0.001 vs. HAART alone, 2-sided Fishes exact test.

CONCLUSIONS: In this largest prospective randomized study of IL-2 in advanced HIV patients to date, significant increases in CD4+ counts were seen with both CIV and SC IL-2 compared to HAART alone after 60 wks of therapy, which continued to increase and grow larger to week 84. Additional virology and immunologic assessment are in progress.

2001-02-04
17

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.