A common anti-cytomegalovirus drug, ganciclovir, inhibits HIV-1 replication in human tissues ex vivo. (17th July 2017)

• Record Type: Journal Article
• Authors: Vanpouille, Christophe; Bernatchez, Jean A.; Lisco, Andrea; Arakelyan, Anush; Saba, Elisa; Götte, Matthias; Margolis, Leonid
• Is Part Of: AIDS. Volume 31:Number 11(2017)
• Publication Date: 2017-07-17
• Subjects: cytomegalovirus -- delayed-chain termination -- ganciclovir -- HIV-1 -- reverse transcriptase; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001532
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Background: Cytomegalovirus (CMV) is a common HIV-1 copathogen. Since CMV infection is an important contributor to immune activation, the driving force of HIV disease, an anti-CMV strategy might be beneficial to HIV-infected patients. Shin et al . ( J Acquir Immune Defic Syndr 2014; 65:251–258) reported that anti-CMV therapy with valganciclovir in coinfected individuals results in a decrease of HIV viral load that is not accompanied by a decrease of immune activation. This suggests an alternative mechanism for HIV inhibition other than suppression of CMV-mediated inflammation. Method: We evaluated the anti-HIV activity of ganciclovir (GCV), the active form of valganciclovir, on HIV replication in human tissues ex vivo . Results: We show that GCV has a direct suppressive activity on HIV replication in human tissues ex vivo, including laboratory strains, drug-resistant and primate HIV-1 isolates. We deciphered the mechanism of this inhibition and showed that GCV-TP is incorporated in the nascent DNA chain and acts as a delayed chain terminator. Conclusion: Our results suggest that anti-CMV strategy using valganciclovir in HIV-1-infected individuals may reduce HIV-1 viral load not only indirectly by decreasing CMV-mediated immune activation but also directly by inhibiting HIV-1 reverse transcriptase. Abstract : Supplemental Digital Content is available in the text