The retrovirus that causes Acquired Immune Deficiency Syndrome (AIDS) was first identified in 1983 and later became known as the Human Immunodeficiency Virus (HIV). According to the UNAIDS (the Joint United Nations Program on HIV/AIDS), in 2003, 38 million people were infected with HIV, 5 million of which were newly infected, and 3 million people died from AIDS.

The treatment of HIV has been revolutionized since the introduction of highly active antiretroviral (HAART) therapy and improved patient survival. The global market for HIV antiretrovirals was valued at $6.6 billion in 2004, with the U.S. accounting for approximately 70% of this value. The drug combination of Sustiva and Combivir is currently the preferred regimen for newly treated patients, but we expect this to change in the near future as Truvada gains traction and eventually supplant Combivir as the dominant dual nucleoside fixed dose combination.

Despite the success of HAART in extending patient survival, new antiretroviral drugs are needed to combat the increasing emergence of drug-resistant HIV strains and to provide drugs that can be better tolerated. Newer generation non-nucleosides (GW695634 and TMC125), nucleosides (Reverset), and protease inhibitors (TMC114) are designed to combat drug resistance and indeed are demonstrating activity against common HIV mutation strains. Because of their ability to overcome resistance, we believe these newer agents will most likely be used in the second or third line setting in patients who have developed resistance to the preferred front-line regimen.

Another strategy for overcoming drug resistance is to target different aspects in the HIV infection cycle. There a numerous drugs in development that are attempting to do so and of these, the entry inhibitors that block HIV binding to the CD4 receptor (BMS-488043 and TNX-355) and those that block HIV binding to the CCR co-receptors are furthest in development. The CCR5 inhibitors (Maraviroc, Vicriviroc and GW873140) in particular, have been eagerly awaited because of their novel mechanism of action. However, due to the potential for co-receptor switching to more aggressive HIV strains, we are cautious of this class of drugs until their long-term safety can be established.

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