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About the Authors:
Jorge A. Tavel
* E-mail: [email protected]
Affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
INSIGHT STALWART Study Group
¶Membership of the Writing Group and the STALWART Study Group is provided in the Acknowledgments.
Introduction
Antiretroviral therapy (ART) has led to significant suppression of HIV replication and improvement in both morbidity and mortality in patients with HIV-infection [1]–[3]. However, despite maximal viral suppression, viral eradication has not been achieved and viremia recurs in patients after treatment interruption [4]–[6]. Moreover, ART therapy is associated with significant toxicities, important interactions with other medications, difficulties in maintaining rigorous adherence, and its efficacy is limited by the emergence of drug resistant HIV variants [7]–[9]. Once ART has been started, lifelong therapy is required since treatment interruptions are associated with an increased risk of disease progression or death [10]. These limitations of ART have underscored the need to explore adjuvant or alternative therapeutic strategies for the treatment of HIV infection.
A number of randomized controlled trials have shown that the use of recombinant interleukin-2 (IL-2) with ART leads to significant and sustained increases in CD4+ counts in HIV-infected patients [11]–[22]. Although the use of IL-2 with antiretrovirals in the pre-ART era was associated with transient rises in plasma HIV RNA levels in some study participants, no clinical trial of IL-2 in HIV-infected patients has demonstrated a significant sustained increase in either plasma HIV RNA or intracellular HIV DNA in IL-2 recipients compared to controls. In fact, one randomized study actually showed a larger decrease in viral load after one year in participants given IL-2 and ART compared to those who received ART alone [22]. Similarly, a pooled analysis of long-term follow-up data from 3 randomized controlled trials showed that IL-2 used with combination ART produced significant decreases in viral load after a median of 30 months compared to ART alone [23]. While the success observed in increasing CD4+ counts without increasing viral load suggests IL-2 may be an effective strategy to complement the effects of ART in HIV-infected patients, it also raises the question of whether IL-2 can be used to maintain CD4+ counts while sparing the use of ART.
One small pilot trial, the United Kingdom Vanguard...