Chemokine receptors--future therapeutic targets for HIV?

To date, triple drug therapies for HIV have resulted in spectacular reductions in the number of virus particles and often remarkable recovery from disease in infected people. There is still, however, a great need for improved therapies. A battery of drugs aimed at different stages in the life cycle of HIV will enable switching of treatments if resistant viruses emerge or if patients are unable to tolerate particular therapies. Intense efforts are now underway to produce drugs that target chemokine receptors used by HIV to gain entry into cells. HIV needs two receptors on the host cell surface for efficient attachment and infection. HIV first interacts with CD4 but requires a coreceptor to penetrate the cell membrane. The first coreceptor, identified in 1996, is a member of the family of chemokine receptors, members of the G-protein coupled 7TM superfamily, which are involved in the trafficking of leukocytes in immune surveillance and inflammation. Such a therapeutic approach would differ from those used successfully to date, which focus largely on proteins coded by the HIV virus itself, and which are required for the replicative cycle of the virus. Many small, orally bioavailable molecules that block various 7TM receptors are used to treat a panoply of diseases including ulcers, allergies, migraines, and schizophrenia. These molecules are the cornerstone of the pharmaceutical industry's contribution to the fight against so many diseases, and it is hoped that a small molecule inhibitor of coreceptors can be developed that will become an invaluable drug in the fight against AIDS.