Acquired immunodeficiency syndrome drug development

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

The Orphan Drug Act of 1983 was passed to encourage die development and marketing of products used to treat rare diseases. The act defines a rare disease as a condition affecting fewer than 200,000 individuals in die United States. The National Organization of Rare Disorders reports that there are more tiian 6000 rare disorders that affect approximately 25 million individuals. Examples of rare disorders include Tourette s syndrome, ovarian cancer, acquired immunodeficiency syndrome (AIDS), Huntington s disease, and certain forms of leukemia... 

Human immunodeficiency virus (HIV) is a single-stranded RNA retrovirus that causes acquired immunodeficiency syndrome (AIDS), a condition in which individuals are at increased risk for developing certain infections and malignancies. The virus is found in two major forms HIV-1, the most prevalent worldwide, and HIV-2, the most common in western Africa. More than 22 million people have died of HIV infection, and 40 million are believed to be infected worldwide. AIDS epidemics threaten populations in sub-Saharan Africa, Southeast Asia, Central and South America, and Russia. In the United States about 450,000 deaths have occurred and another 900,000 people are estimated to carry the virus. Although the development of new drugs, complex multidrug regimens, and behavioral modification have done much to combat the spread of HIV in-... 

The human immunodeficiency virus (HIV) is one of only a few retroviruses known to infect humans. It is estimated that approximately twenty-two million people are now infected worldwide [1]. With only a tiny number of exceptions, infection ultimately leads to the development of the lethal condition of acquired immunodeficiency syndrome, or AIDS. To date, only a handful of drugs have been shown to have any effect on the course of the disease. These are, in general, relatively ineffective at significantly prolonging life, and drug resistance develops rapidly. Equally discouraging, vaccines have not yet been developed to prevent infection. 

Note The treatment of mycobacterial infections has become an even more important and challenging problem because of the emergence of multiple-drug-resistant organisms and because of the acquired immunodeficiency syndrome (AIDS) pandemic, which has been associated with a marked increase in tuberculosis and infection caused by the M. avium complex. Because the microorganisms grow slowly and the diseases often are chronic, patient compliance, drug toxicity, and the development of microbial resistance present special therapeutic problems. 

Efavirenz (DMP 266) (1) is an effective non-nucleoside inhibitor of reverse transcriptase of the human immunodeficiency virus (HIV) recently registered by the US Food Drug Administration (FDA) for treatment of the acquired immunodeficiency syndrome (AIDS).1 2 3 Inhibition of HIV reverse transcriptase by nucleosides like azidothymidine (AZT) (2) is a proven therapy for delaying the progression to AIDS. However, the rapid viral mutation to resistant strains requires the development of new therapeutic agents. The recent development of both protease inhibitors and non-nucleoside reverse transcriptase inhibitors offers hope of effective treatment especially when coadministered. 

Cys202 [208]. Human immunodeficiency virus (HIV) is the primary cause of acquired immunodeficiency syndrome (AIDS). In an effort to find new drugs preventing the growth of HIV, Masao et al developed an in vitro assay method of RNase H activity associated with reverse transcriptase (RT) from HIV-1. Some 1,4-naphthoquinones moderately inhibited RNase H activity [209]. Several natural occurring naphtoquinones have showed antiretroviral activity [210-211],... 

The public is aware of acquired immunodeficiency syndrome (AIDS) because it is a disease that travels" h human carriers and has infected and killed prominent people who are citizens in economically developed countries Nevertheless, compare the 2001 figures for AIDS and nu-laria. After approximately 20 years. 40 million people haw been infected with the human immunodeficiency iiii (HIV), of whom S million were infected and 3 million dial in 2001. For North America. 940.000 have become infetia in the past 20 years, of whom 45.(XX) were infected anJ 20.000 died in 2001. In contrast, approximately W ofik world s population has malaria (300 to 500 million). 0 the.se. about I million will die annually most an children. In contrast, there are only about 1.500 new ea.ses of malan annually in the United States, and nearly all of these com from travelers arriving from areas where malaria is endemic Most prescriptions for antimalarial drugs arc for prophylat -of travelers going to. and coming from, areas of die odJ where malaria is endemic. 

Historically, the development of antiviral drugs has been slow when compared with the development of other antimicrobial drugs. This was probably because the majority of viral infections are eliminated by the host s immune system. With the advent of the HIV and acquired immunodeficiency syndrome (AIDS) that follows infection with HIV, many new antiviral drugs have been introduced since the end of the 1990s. As more is known about how viruses replicate inside cells and how they affect cell function, then no doubt more antiviral dmgs will be developed. 

Abstract Acquired immunodeficiency syndrome (AIDS) and its related disorders, caused by retrovirus human immunodeficiency virus (HIV) are a major health concern worldwide. HIV protease is one of the major viral targets for the development of new chemotherapeutics. Currently, many HIV protease inhibitors are used in combination with HIV reverse transcriptase inhibitors. However, the use of current drugs regimens has several shortcomings, such as adherence, tolerability, long-term toxicity and drug- and... 

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