Antiretroviral drugs do not interfere with bryostatin-mediated HIV-1 latency reversal.

Abstract

Although an effective combination of antiretroviral therapy (cART) controls HIV-1 viraemia in infected patients, viral latency established soon after infection hinders HIV-1 eradication. It has been shown that bryostatin-1 (BRY) inhibits HIV-infection in vitro and reactivates the latent virus through the protein kinase C-NF-κB pathway. We determined the in vitro potential effect of BRY in combination with currently used antiretroviral drugs. BRY alone or in combination with maraviroc (MVC)/Atripla (ATP) was tested for its capacity to reactivate latent virus and inhibit new infections. JLTRG-R5 cells and two latent HIV-1-infected cell lines, J89GFP and THP89GFP, were used as latency models. To quantify HIV infection, the reporter cell line TZM-bl was used. We found that BRY reactivates HIV-1 even in combination with MVC or ATP. Antiretroviral combinations with BRY do not interfere with BRY activity (i.e., the reactivation of latently infected cells) or with the antiviral activity of antiretroviral drugs. In addition, BRY-mediated down-modulation of surface CD4 and CXCR4 was not affected when it was used in combination with other antiretrovirals, and no hyperactivation or high-proliferation effects were observed in primary T cells. Moreover, the BRY treatment was able to reactivate HIV-1 in CD4+ T cells from HIV-1-infected patients under cART. Thus, we propose the use of BRY to purge the viral reservoir and recommend its combination with current antiretroviral treatments.

• Authors: Marta Martínez-Bonet, Maria Isabel Clemente, Susana Álvarez, Laura Díaz, Dolores García-Alonso, Eduardo Muñoz, Santiago Moreno, Maria Ángeles Muñoz-Fernández
• Journal: Antiviral research (Antiviral Res) Vol. 123 Pg. 163-71 (Nov 2015) ISSN: 1872-9096 [Electronic] Netherlands
• PMID: 26427554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Retroviral Agents
• Bryostatins
• Cyclohexanes
• Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Triazoles
• Maraviroc

Topics

• Adult
• Anti-Retroviral Agents (metabolism)
• Bryostatins (metabolism)
• CD4-Positive T-Lymphocytes (drug effects, virology)
• Cells, Cultured
• Cyclohexanes (metabolism)
• Drug Interactions
• Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination (metabolism)
• HIV-1 (drug effects, physiology)
• Humans
• Male
• Maraviroc
• Middle Aged
• Triazoles (metabolism)
• Virus Latency (drug effects)