Email updates

Keep up to date with the latest news and content from Retrovirology and BioMed Central.

Open Access Highly Accessed Research

Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS

Iart Luca Shytaj1, Barbara Chirullo1, Wendeline Wagner2, Maria G Ferrari3, Rossella Sgarbanti4, Alessandro Della Corte1, Celia LaBranche5, Lucia Lopalco6, Anna Teresa Palamara78, David Montefiori5, Mark G Lewis2, Enrico Garaci1 and Andrea Savarino1*

Author Affiliations

1 Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy

2 BIOQUAL, Inc., 9600 Medical Center Drive, Rockville, MD 20850, USA

3 ABL, Rockville, MD 20850, USA

4 Università Telematica San Raffaele, via di val Cannuta 247, Rome, Italy

5 Duke University, Durham, North Carolina, USA

6 San Raffaele Scientific Institute, Milan, Italy

7 Department of Public Health and Infectious Diseases, Institute Pasteur, Cenci-Bolognetti Foundation, “Sapienza”, University of Rome, Rome, Italy

8 San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, Rome, Italy

For all author emails, please log on.

Retrovirology 2013, 10:71  doi:10.1186/1742-4690-10-71

Published: 16 July 2013

Abstract

Background

HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia.

Results

We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8+ cells and associated with enhanced levels of cell-mediated immune responses.

Conclusions

The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current “ART for life” plight.

Keywords:
Functional cure of HIV/AIDS; Viral reservoirs; Eradication research; Antireservoir therapy; Auranofin; Buthionine sulfoximine; SIVmac251 infection; Macaque AIDS model