Immunotherapy in HIV infection; current and future challenges
- Yves Lévy1
© Lévy; licensee BioMed Central Ltd. 2010
Published: 11 May 2010
Administration of HAART has resulted in significant improvements in the survival of HIV-infected patients. However, despite now reaching a point where we can achieve durable, maximal suppression of plasma viral load in most of our HAART-treated patients, non-AIDS-related morbidity and mortality among these patients remain a concern. Conditions typical of aging, such as cardiovascular disease and cancer, are seen at a higher rate in HIV-infected patients compared to the general population, potentially because the ability of HAART to restore immunocompetence appears incomplete--even in patients who have long-term undetectable HIV-1 RNA.
New insights into the pathogenesis of HIV-1 infection highlight several new and promising areas of investigation for immune-based therapies, including strategies that target T-cell homeostasis and immune activation, as well those targeted at restoring immune responses directed against HIV.
The rationale behind the investigation of a of cytokines such as IL-2 and IL-7 as adjunctive therapies to antiretroviral treatment is to improve the restoration of the immune system and improve HIV-directed immune responses. Among cytokines, IL-2, was extensively studied in several phase II and two large phase III studies. Results from these studies showed that IL-2 increases signficantly CD4 counts in the long term. However, this biological effect did not translate into clinical benefit. These results raise several questions about the functionality of IL-2 expanded CD4 T cells that will be discussed.
The potential interest of IL-7 is based on its crucial role on T cell homeostasis both in thymic output and peripheral T proliferation and survival. This new promising cytokine is currently under evaluation is several I/II clinical trials in chronically HIV-infected patients with low level of immune restoration despite controlled viral load. Results from these studies will be presented and discussed.
This article is published under license to BioMed Central Ltd.