Chloroquine and Hydroxychloroquine as Inhibitors of Human Immunodeficiency Virus (HIV-1) Activity

Abstract

Recent advances in the development of antiretrovirals have significantly extended life-spans and positively impacted morbidity of HIV-seropositive patients. While effective, antiretrovirals are associated with complex medication regimens, large pill burdens, and significant side effects which may impact quality of life. Researchers continue to examine various chemical entities in their search for agents with anti-HIV activity. Ideal agents would be efficacious, easily dosed and administered, inexpensive, and with few adverse effects. Chloroquine and its analog hydroxychloroquine are two inexpensive agents that are widely used for the treatment of malaria and have been shown to achieve some level of anti-HIV activity. The exact mechanism of chloroquine and hydroxychloroquine's anti-HIV activity has not yet been discerned but may be related to effects on HIV's surface envelope glycoprotein 120. If found efficacious, both drugs would offer significant advantages to current therapy including a unique mechanism of action, lack of cross-resistance with other antiretrovirals, and low cost. Early and limited in vitro and in vivo data have demonstrated modest anti-HIV efficacy as indicated by measures of viral burden. Effects on CD4+ cell counts have not been as pronounced. It is premature to advocate the use of either of these agents in the management of routine HIV disease; however; the drugs should be further studied to determine their benefit in the treatment of patients who have exhausted all standard treatments. Larger, well-controlled trials are needed to discern the potential role of chloroquine and hydroxychloroquine in the management of HIV.

Blocked Autophagy Using Lysosomotropic Agents Sensitizes Resistant Prostate Tumor Cells to the Novel Akt Inhibitor AZD5363

“…Chloroquine has been used for decades for the treatment of malaria and rheumatoid arthritis, and has been shown to achieve some level of anti-HIV activity (50). Chloroquine is also known to be an inhibitor of autophagy by blocking acidification of the lysosome, preventing fusion with autophagosome (51) and, thus, represents a clinical opportunity.…”

Inhibition of Encephalomyocarditis Virus and Poliovirus Replication by Quinacrine: Implications for the Design and Discovery of Novel Antiviral Drugs

“…TBSV RNA accumulation was inhibited by QC both in plants and in protoplasts (42). In addition, QC and some other structurally similar intercalating antimalarial drugs, such as chloroquine and hydroxychloroquine, were suggested to have some antihuman immunodeficiency virus (HIV) effects (23,38). These studies, together with the results reported here, indicate that QC or QC-like molecules might be effective tools to inhibit replication of various positive-sense RNA viruses that rely on translation initiation from highly structured IRES elements in their genomes.…”

Evaluation of Immunomodulators, Interferons and Known in Vitro SARS-CoV Inhibitors for Inhibition of SARS-Cov Replication in BALB/c Mice

“…The drug has also been shown to prevent the up-regulation of major histocompatibility complex (MHC) I antigens and cellular abnormalities in coxsackie B4-infected human foetal thymocytes (Brilot et al, 2004). The mechanism of inhibition for HIV may be related to some inhibitory interaction with gp120 (Romanelli et al, 2004) or inhibition of the inflammatory cytokine response to HIV (Rayne et al, 2004). This mechanism may be important in treating SARS-CoV, since the virus induces a severe inflammatory response in the lungs of patients (Yen et al, 2006).…”