Antiretroviral drug development for HIV: challenges for the future.

The scarcity of new innovative drugs in the development pipeline for combating HIV replication may signal a change in direction for HIV researchers and drug developers. The model of introducing drugs with incremental improvements within existing drug classes is no longer commercially viable. While an argument can be made that drugs aimed at novel targets may have a greater impact, the list of such targets is limited and the scientific challenge of intervening at another stage in the HIV replication cycle is high. It is difficult to envision a realistic risk/reward scenario that will ensure continued investment in the discovery of novel HIV drugs that simply block replication and suppress plasma viral load. Recently, it has been suggested that the scientific community should move research in a new direction, with the goal of attacking the reservoirs of latent HIV that persist despite treatment with current drugs to achieve a functional cure, if not a sterilizing cure. This process will have to be a long-term commitment, primarily funded by the NIH, with some involvement by the pharmaceutical and biotechnology industries. While most individuals infected with HIV can achieve viral suppression with the current approved therapies, treatment is lifelong, side effects are significant and resistance will eventually render more of these drugs less effective. New and innovative approaches must be developed to prevent viral infection and further improve the quality of life for those individuals who are already infected.