HIV Integrase

HIV INTEGRASE: A MAJOR NEW DRUG TARGET FOR HIV INFECTION

According to World Health Organisation statistics HIV has become the fourth largest cause of death globally. There are an estimated 40 million HIV sufferers worldwide, with around 900,000 in the United States and 600,000 in Western Europe.

Although the introduction of anti-viral drugs has improved life expectancy and slowed disease progression, HIV rapidly becomes resistant to these drugs. Around 270,000 patients in the United States are resistant to at least one class of HIV drug, and around 50,000 have developed resistance to all three current drug classes. In addition to new classes of drugs to overcome resistance, there is also a need for new drugs with an improved side-effect profile and/or easier administration. The discovery of new classes of anti-viral drugs (especially those against new targets) provides, perhaps, the only hope of treatment for an increasing number of patients.

Therapeutic Potential

Since the development of the first HIV reverse transcriptase inhibitors, new classes of inhibitors (such as the protease inhibitors and the non-nucleoside inhibitors) have been developed, and each new class has expanded the total HIV market as patients are treated with several drugs simultaneously. In addition to new drugs classes, several additional drugs in the same existing classes have been successfully developed, with each capturing significant market share.

To date there is no integrase inhibitor on the market. Given the success of drugs that inhibit the two other HIV enzymes (reverse transcriptase and protease), there is every reason to believe that the first, second, third and following integrase inhibitors to reach the market could be expected to achieve significant sales.

Project Status

A series of lead compounds has been generated through high throughput screening assays and these compounds are presently being optimized using comprehensive cellular assays and molecular modelling techniques to select a lead molecule for preclinical testing.

Scientific Rationale

The replication cycle of HIV contains a number of enzymes/processes which are essential for viral replication and which are therefore good targets for the discovery of anti-HIV drugs. Effective inhibitors have been developed to target the fusion event, the reverse transcriptase (RT) enzyme and the protease (PR) enzyme. HIV integrase is the third enzyme encoded by HIV, and Avexa expects inhibitors of HIV integrase may be as successful at controlling HIV disease as the RT and PR inhibitors already on the market.