Exploiting the Anti-HIV-1 Activity of Acyclovir: Suppression of Primary and Drug-Resistant HIV Isolates and Potentiation of the Activity by Ribavirin

• Published in: Antimicrobial Agents and Chemotherapy Vol. 56; no. 5; pp. 2604 - 2611
• Main Authors: Vanpouille, Christophe, Lisco, Andrea, Introini, Andrea, Grivel, Jean-Charles, Munawwar, Arshi, Merbah, Melanie, Schinazi, Raymond F, Derudas, Marco, McGuigan, Christopher, Balzarini, Jan, Margolis, Leonid
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.05.2012
• Subjects: Acyclovir; Acyclovir - pharmacology; Anti-HIV Agents; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral Agents; antiviral properties; Biological and medical sciences; Cell Line; Clinical trials; combination drug therapy; Data processing; DNA; drug effects; Drug resistance; Drug Resistance, Viral; Drug Resistance, Viral - drug effects; Drug Synergism; drugs; Elongation; guanine; Herpes simplex virus 2; highly active antiretroviral therapy; HIV Fusion Inhibitors; HIV Fusion Inhibitors - pharmacology; HIV infections; HIV Infections - virology; HIV-1; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Lamivudine; Lamivudine - pharmacology; Medical sciences; Nevirapine; Nevirapine - pharmacology; nucleoside reverse transcriptase inhibitors; Palatine Tonsil; Palatine Tonsil - drug effects; Palatine Tonsil - virology; patients; pharmacology; Pharmacology. Drug treatments; physiology; Potentiation; Protease Inhibitors; Protease Inhibitors - pharmacology; Proteinase inhibitors; Replication; Ribavirin; Ribavirin - pharmacology; Survival; T-Lymphocytes; T-Lymphocytes - drug effects; T-Lymphocytes - virology; Tissue Culture Techniques; valacyclovir; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; virology; virus replication; Zidovudine; Zidovudine - pharmacology; Potentiation; Immunopathology; Acyclic nucleoside; Purine nucleoside; Antiretroviral agent; Treatment resistance; HIV-1 virus; Suppression; Retroviridae; AIDS; Immune deficiency; Lentivirus; Biological activity; Ribavirin; Infection; Virus; Viral disease; Primary; Aciclovir; Nucleoside analog; Antiviral; Isolate; Human immunodeficiency virus; DNA polymerase inhibitor
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/AAC.05986-11

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.