The Virus. 

HIV- The Pandemic

More than 60 million people worldwide have been infected with HIV to date, with over 25 million of these individuals having died of AIDS.  In 2005 alone, approximately five million people became infected at a rate of approximately 13,600 new infections a day, almost all of which are occurring outside of the U.S. and Europe.  It is estimated that only one person in ten in Africa and one in seven in Asia in need of HIV antivirals were receiving it in mid-2005, and less than one in five people worldwide at risk of becoming infected with HIV has access to basic prevention services.  This is in spite of a $7.7 billion increase in annual global funding for HIV research and prevention activities between 1996 ($300 million) and 2005 ($8 billion).  The Joint United Nations Programme on HIV/AIDS estimates that $15 billion will be needed to effectively respond to the HIV/AIDS epidemic in low- and middle-income countries in 2006, with this figure rising to $22 billion in 2008.

Current estimates also suggest that 30% to 50% of people infected with HIV eventually develop resistance to one or more HAART drug combinations.  If new therapies are not introduced soon, this percentage is expected to increase rapidly in the coming years, possibly culminating in a “second wave” of AIDS deaths due to drug failure in the developed world.  There is currently no cure for HIV, and existing therapies can only work for so long before new solutions are needed.  In other words, HIV is not just a problem of the developing world. 

HIV - Viral Entry. 

HIV is a retrovirus (a membrane-bound RNA virus) coated with spikes created by trimers of its envelope protein.  HIV invades a susceptible cell in a multi-step process that uses these envelope spikes to mediate fusion between the membranes of the virus and the target cell.  This process begins when a specific glycoprotein within the HIV envelope spike, referred to as gp120, binds with a specific receptor found on the surface of T-cells, macrophages and dendritic cells, referred to as CD4.  This interaction prompts gp120 to alter its shape to reveal a second site within the glycoprotein that binds to a chemokine receptor called CCR5 or CXCR4.  This second interaction prompts another series of structural changes within the HIV envelope spike to reveal gp41, a glycoprotein that tethers together the viral and target cell membranes and draws them closer until they fuse and HIV’s genetic material is released into the cytoplasm of the target cell.  Preventing this entire process is possible using reagents that block HIV from binding to CD4 and/or CCR5 or CXCR4, or that interfere with viral-target cell membrane fusion.

HIV – AIDS

HIV, like all viruses, exists only to reproduce.  It does this by invading living cells and hijacking their cellular machinery to produce more viruses.  In the initial, Acute Phase of the disease, HIV production from infected cells quickly outpaces the body’s defensive immune response.  The human immune response eventually dampens HIV production, but it is unable to eradicate it completely, leading to a stand-off between the host’s immune defenses and HIV viral production. 

HIV primarily uses activated memory T-cells (T-cells specific to previously encountered pathogens) for viral production, the death of which slowly creates a defect in the immune system.  In fact, based on research performed with SIV-infected rhesus macaques, it is estimated that over 50% of all memory CD4+ T-cells are destroyed by viral infection during the Acute Phase of disease.  As a result, the host’s immune defenses are eventually rendered helpless in fighting even the most innocuous of pathogens, and the host develops Acquired Immunodeficiency Syndrome (AIDS).  The following chart illustrates the various phases of HIV disease:

Individuals infected with HIV typically reach their peak viral load within 14 days of infection, but might remain in the Acute Phase of the disease for several months before the immune defenses establish equilibrium with viral production (termed the viral “set point”).  Most individuals undergoing HIV treatment are able to remain in the Progressive Phase for one to ten years; however, certain infected individuals have been able to control their infection and remain at their viral set point for longer than 15 years, even without treatment.  

(Sources: www.iavi.org; “Financing the Response to HIV/AIDS in Low and Middle Income Countries: Funding for HIV/AIDS from the G7 and the European Commission,” The Henry J. Kaiser Family Foundation, July 2005; UNAIDS/World Health Organization AIDS epidemic update: December 2005)