Exploiting the Anti-HIV-1 activity of acyclovir: Suppression of primary and drug-resistant HIV isolates and potentiation of the activity by Ribavirin

Vanpouille, Christopher, Lisco, Andrea, Introini, Andrea, Grivel, Jean-Charles, Munawwar, Arshi, Merbah, Melanie, Schinazi, Raymond F., Derudas, Marco, McGuigan, Christopher ORCID: https://orcid.org/0000-0001-8409-710X, Balzarini, Jan and Margolis, Leonid 2012. Exploiting the Anti-HIV-1 activity of acyclovir: Suppression of primary and drug-resistant HIV isolates and potentiation of the activity by Ribavirin. Antimicrobial Agents and Chemotherapy 56 (5) , pp. 2604-2611. 10.1128/AAC.05986-11

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Abstract

Multiple clinical trials have demonstrated that herpes simplex virus 2 (HSV-2) suppressive therapy using acyclovir (ACV) or valacyclovir in HIV-1/HSV-2-infected persons increased the patient's survival and decreased the HIV-1 load. It has been shown that the incorporation of ACV-monophosphate into the nascent DNA chain instead of dGMP results in the termination of viral DNA elongation and directly inhibits laboratory strains of HIV-1. We evaluated here the anti-HIV activity of ACV against primary HIV-1 isolates of different clades and coreceptor specificity and against viral isolates resistant to currently used drugs, including zidovudine, lamivudine, nevirapine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs), a fusion inhibitor, and two protease inhibitors. We found that, at clinically relevant concentrations, ACV inhibits the replication of these isolates in human tissues infected ex vivo. Moreover, addition of ribavirin, an antiviral capable of depleting the pool of intracellular dGTP, potentiated the ACV-mediated HIV-1 suppression. These data warrant further clinical investigations of the benefits of using inexpensive and safe ACV alone or in combination with other drugs against HIV-1, especially to complement or delay highly active antiretroviral therapy (HAART) initiation in low-resource settings.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0066-4804/ (accessed 24/02/2014)
Publisher:	American Society for Microbiology
ISSN:	0066-4804
Date of First Compliant Deposit:	30 March 2016
Last Modified:	10 May 2023 21:09
URI:	https://orca.cardiff.ac.uk/id/eprint/32133

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