Repurposing medications for use in treating HIV infection: A focus on valproic acid as a latency-reversing agent

Abstract

What is known and objective: Combined antiretroviral therapy (ART) reduces human immunodeficiency virus type 1 (HIV-1) RNA plasma levels below the limit of detection. However, HIV-1 persists in latently infected CD4+ T cells, which is currently the barrier to curing HIV-1. Novel mechanisms are being explored to target HIV-1 latent reservoirs. The purpose of this review was to critically evaluate the available literature on innovative use of valproic acid (VPA) for the agent's therapeutic effects on reversing latent human immunodeficiency virus (HIV) reservoirs. Methods: A search of PubMed (1996-December 2017) and International Pharmaceutical Abstracts (1970-December 2017) was conducted using the MeSH terms HIV, valproic acid and latency. Free text searches included the terms latency-reversing agents, HIV therapy and valproic acid. Results: Six clinical trials and one case report were critically evaluated on VPA's therapeutic effects on reversing HIV reservoirs. Only one study reported that VPA therapy has a significant effect on reversing HIV-1 latent reservoirs; all other studies reviewed and did not demonstrate an appreciable effect of VPA on reversing HIV latent reservoirs. What is new and conclusion: Current literature does not support the use of VPA as adjunctive therapy to reverse HIV-1 latent reservoirs. Sample sizes were small, and overall studies were not sufficiently powered. Further studies are needed to make informed conclusions on the use of VPA as an HIV-1 latency-reversing agent.