Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
Open Access
- 16 July 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Retrovirology
- Vol. 10 (1), 71-15
- https://doi.org/10.1186/1742-4690-10-71
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
This publication has 47 references indexed in Scilit:
- Macrophages and their relevance in Human Immunodeficiency Virus Type I infectionRetrovirology, 2012
- Therapeutic imprinting of the immune system: towards a remission of AIDS in primates?Retrovirology, 2012
- Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawalRetrovirology, 2012
- Nonpathogenic Simian Immunodeficiency Virus InfectionsCold Spring Harbor Perspectives in Medicine, 2011
- Breaking Free of Sample Size Dogma to Perform Innovative Translational ResearchScience Translational Medicine, 2011
- Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapyRetrovirology, 2010
- Modeling Latently Infected Cell Activation: Viral and Latent Reservoir Persistence, and Viral Blips in HIV-infected Patients on Potent TherapyPLoS Computational Biology, 2009
- HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferationNature Medicine, 2009
- "Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescenceRetrovirology, 2009
- Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaquesProceedings of the National Academy of Sciences of the United States of America, 2007