Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study

TY - JOUR

T1 - Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study

AU - Tavel, Jorge A

AU - INSIGHT STALWART Study Group

AU - Babiker, Abdel

AU - Fox, Lawrence

AU - Gey, Daniela

AU - Lopardo, Gustavo

AU - Markowitz, Norman

AU - Paton, Nicholas

AU - Wentworth, Deborah

AU - Wyman, Nicole

PY - 2010/2/23

Y1 - 2010/2/23

N2 - Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions: IL-2 alone or with peri-cycle HAART increases CD4+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4+ cells. Trial Registration: ClinicalTrials.gov NCT00110812.

AB - Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions: IL-2 alone or with peri-cycle HAART increases CD4+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4+ cells. Trial Registration: ClinicalTrials.gov NCT00110812.

U2 - 10.1371/journal.pone.0009334

DO - 10.1371/journal.pone.0009334

M3 - Journal article

C2 - 20186278

SN - 1932-6203

VL - 5

SP - e9334

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 2

ER -