Methods for Treatment of HIV or Malaria Using Combinations of Chloroquine and Protease Inhibitors

Abstract

The present invention relates to a drug combination capable of conferring therapeutic benefits in the treatment of both AIDS and malaria. In particular, it relates to a drug combination including at least one quinolinic antimalarial compound such as chloroquine or hydroxychloroquine, and at least one inhibitor of the Human Immunodeficiency Virus (HIV) protease enzyme. This drug combination is capable of inhibiting the replication of both HIV and Plasmodium sp. It also relates to the direct antimalarial effects of the HIV PIs.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This patent application is a divisional of U.S. patent application Ser. No. 10 / 783,268, filed Feb. 20, 2004, entitled: “Methods for Treatment of HIV or Malaria Using Combinations of Chloroquine and Protease Inhibitors”, which claims the benefit of U.S. provisional application Ser. No. 60 / 449,517 filed on Feb. 21, 2003 and U.S. provisional patent application Ser. No. 60 / 471,038 filed on May 16, 2003, all of which are incorporated herein in their entirety.INCORPORATION BY REFERENCE[0002]In addition, the following Sequence Listing material is contained on a disc, and the files are hereby incorporated-by-reference into the present application in their entirety: Savarino Sequence Listing, PatentIn Document, 2 KB, created Sep. 21, 2004; Savarino Sequence Listing, Microsoft Word Document, 41 KB, created Sep. 21, 2004; Savarino Sequence Listing, Text Document, 6 KB, created Sep. 21, 2004. Print copies of the Sequence Listings are included as an A...

AI Technical Summary

Benefits of technology

[0018]The combination claimed in the present patent application unexpectedly demonstrated enhanced capability of conferring a more sustained inhibition of both HIV and Plasmodium sp. than the single agents administered alone, that is, CQ can reinforce the antiretroviral activity of a PI and a PI can strengthen the antimalarial activity of CQ.

[0021]Also, the combination of CQ and PIs can be used to restore the sensitivity of drug-resistant isolates of HIV and P. falciparum to the PIs and to CQ, respectively.

Problems solved by technology

The effects of these diseases are most pronounced in underdeveloped countries in that the diseases are accompanied by financial and living conditions that are already miserable to start with.

Several resource-poor countries cannot afford effective therapies that might allow the prevention of many deaths.

The difficulties per se in treating both AIDS and malaria, caused in part by the drug-resistance of both their etiological agents, i.e., the human immunodeficiency viruses (HIV) and protozoa belonging to the genus Plasmodium, become exaggerated when the pharmaceutical weapons are extremely limited.

In several resource-poor countries with high rates of HIV seroprevalence, the use of highly active antiretroviral therapy (HAART) has encountered major obstacles due to its high costs and the complexities of its prescription.

The problem is, however, still far from being solved.

Chloroquine (CQ), recommended for a long time by the World Health Organization (WHO) as a first line treatment of malaria, is still the most affordable and widely adopted antimalarial option in Africa; however, the continuous emergence of drug-resistant Plasmodium strains renders its administration ineffective in a large number of areas in Africa, Latin America and South-Eastern Asia.

Third, erythrocytes parasited by CQ-resistant P. falciparum strains accumulate more limited intracellular CQ pools than those parasited by CQ-sensitive strains.

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