Combined approaches for HIV cure
- PMID: 23446138
- PMCID: PMC3966301
- DOI: 10.1097/COH.0b013e32835ef089
Combined approaches for HIV cure
Abstract
Purpose of review: A serious effort has begun to develop therapies that may be capable of eradicating established HIV infection in man. Because of the biological complexity of HIV infection that persists despite potent antiretroviral therapy, it is widely believed that if such therapies can be developed they will involve complex, multimodality approaches. We highlight some of the recent studies in this effort.
Recent findings: An inhibitor of histone deacetylase has been demonstrated to disrupt latency in man, and new histone deacetylase inhibitors have been identified. Other potential targets, such as histone methyltransferase, protein kinase C, and BRD4, have been recently studied. Model systems, both in primary cells and in animal models, are beginning to be validated. In the clinic, immune-based therapies to aid in the clearance of persistent infection are also being tested.
Summary: It is too early to know what combination eradication therapies for HIV infection will look like in the future, but candidate therapies and model systems to perform preclinical validation are beginning to take shape.
Conflict of interest statement
D.J.H. is an employee of Merck Research Laboratories, who hold the license for the clinical HDAC inhibitor, vorinostat.
Similar articles
-
New approaches in HIV eradication research.Curr Opin Infect Dis. 2011 Dec;24(6):593-8. doi: 10.1097/QCO.0b013e32834cfb2d. Curr Opin Infect Dis. 2011. PMID: 22001946 Review.
-
Latency reversal and viral clearance to cure HIV-1.Science. 2016 Jul 22;353(6297):aaf6517. doi: 10.1126/science.aaf6517. Science. 2016. PMID: 27463679 Free PMC article. Review.
-
HIV reservoirs and strategies for eradication.Curr HIV/AIDS Rep. 2012 Mar;9(1):5-15. doi: 10.1007/s11904-011-0108-2. Curr HIV/AIDS Rep. 2012. PMID: 22249405 Review.
-
The role of latency reversal agents in the cure of HIV: A review of current data.Immunol Lett. 2018 Apr;196:135-139. doi: 10.1016/j.imlet.2018.02.004. Epub 2018 Feb 7. Immunol Lett. 2018. PMID: 29427743 Review.
-
Nanotechnology approaches to eradicating HIV reservoirs.Eur J Pharm Biopharm. 2019 May;138:48-63. doi: 10.1016/j.ejpb.2018.06.002. Epub 2018 Jun 4. Eur J Pharm Biopharm. 2019. PMID: 29879528 Free PMC article. Review.
Cited by
-
HIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat.J Infect Dis. 2014 Sep 1;210(5):728-35. doi: 10.1093/infdis/jiu155. Epub 2014 Mar 11. J Infect Dis. 2014. PMID: 24620025 Free PMC article.
-
HIV: Seeking ultimate victory.Nature. 2015 Jan 15;517(7534):281-2. doi: 10.1038/nature14194. Epub 2015 Jan 7. Nature. 2015. PMID: 25561174 No abstract available.
-
Constellation pharmacology: a new paradigm for drug discovery.Annu Rev Pharmacol Toxicol. 2015;55:573-89. doi: 10.1146/annurev-pharmtox-010814-124551. Annu Rev Pharmacol Toxicol. 2015. PMID: 25562646 Free PMC article. Review.
-
Synergistic Reactivation of Latent HIV Expression by Ingenol-3-Angelate, PEP005, Targeted NF-kB Signaling in Combination with JQ1 Induced p-TEFb Activation.PLoS Pathog. 2015 Jul 30;11(7):e1005066. doi: 10.1371/journal.ppat.1005066. eCollection 2015 Jul. PLoS Pathog. 2015. PMID: 26225771 Free PMC article.
-
Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition.Mol Ther. 2016 Feb;24(2):375-384. doi: 10.1038/mt.2015.210. Epub 2015 Nov 19. Mol Ther. 2016. PMID: 26581160 Free PMC article.
References
-
- Archin NM, Liberty AL, Kashuba AD, et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012;487:482–485. In eight patients, a single dose of 400 mg of the HDAC inhibitor vorinostat induced the upregulation of HIV-RNA expression within resting CD4+ T cells of aviremic HIV-infected patients on ART. - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials