Long-term effects of intermittent IL-2 in HIV infection: extended follow-up of the INSIGHT STALWART Study

Markowitz, Norman, Lopardo, Gustavo, Wentworth, Deborah, Gey, Daniela, Babiker, Abdel, Fox, Lawrence, Tavel, Jorge, Fisher, Martin and for the STALWART Study Group, (2012) Long-term effects of intermittent IL-2 in HIV infection: extended follow-up of the INSIGHT STALWART Study. PloS ONE, 7 (10). e47506. ISSN 1932-6203

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Abstract

BACKGROUND

The Study of Aldesleukin with and without Antiretroviral Therapy (STALWART) was designed to evaluate whether intermittent IL-2 alone or with peri-cycle ART increased CD4+ cell counts (and so delayed initiation of ART) in HIV infected individuals having ≥ 300 CD4+ cells/mm(3) compared to untreated controls. When the results of two large clinical trials, ESPRIT and SILCAAT, showed no clinical benefit from IL-2 therapy, IL-2 administration was halted in STALWART. Because IL-2 recipients in STALWART experienced a greater number of opportunistic disease (OD) or death and adverse events (AEs), participants were asked to consent to an extended follow-up phase in order to assess persistence of IL-2 effects.

METHODOLOGY

Participants in this study were followed for clinical events and AEs every 4 months for 24 months. Unadjusted Cox proportional hazards models were used to summarize death, death or first OD event, and first grade 3 or 4 AE.

PRINCIPAL FINDINGS

A total of 267 persons were enrolled in STALWART (176 randomized to the IL-2 arms and 91 to the no therapy arm); 142 individuals in the IL-2 group and 80 controls agreed to enter the extended follow-up study. Initiation of continuous ART was delayed in the IL-2 groups, but once started, resulted in similar CD4+ cell and viral load responses compared to controls. The hazard ratios (95% CI) for IL-2 versus control during the extension phase for death or OD, grade 3 or 4 AE, and grade 4 AE were 1.45 (0.38, 5.45), 0.43 (0.24, 1.63) and 0.20 (0.04, 1.03), respectively. The hazard ratios for the AE outcomes were significantly lower during the extension than during the main study.

CONCLUSIONS

Adverse events associated with IL-2 cycling did not persist upon discontinuation of IL-2. The use of IL-2 did not impact the subsequent response to initiation of cART.

Item Type: Article
Additional Information: Martin Fisher is part of the STALWART Study Group and not one of the principal authors
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0643 Communicable diseases and public health > RA0644 Individual diseases or groups of diseases, A-Z > RA0644.A25 AIDS. HIV infections
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Depositing User: Ellen Thomas
Date Deposited: 23 Dec 2013 13:16
Last Modified: 06 Mar 2017 17:28
URI: http://sro.sussex.ac.uk/id/eprint/47278

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