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

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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.
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Keywords: chloroquine; hiv; hydroxychloroquine; malaria; treatment

Document Type: Review Article

Affiliations: Assistant Professor of Pharmacy, Clinical Specialist in HIV / AIDS, University of Kentucky College of Pharmacy, 800 Rose Street, Lexington, KY 40536

Publication date: August 1, 2004

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    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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