The process for developing new salvage therapies unfolds in four principal steps. In the second step, the sequences of these two genes are analyzed for resistance mutations and entered into a computer database. At present, this database contains nearly 5,000 sequences from more than 1,000 patients, with some patients having submitted several sequence analyses to the database. The Stanford database is geared primarily to specialized researchers because of its focus on raw sequence data. With the treatment history for every sequenced patient included in the database, this information helps associate mutations with known treatment regimens.
Researchers can also quantify the frequency of specific mutational patterns.
Similarly, three protease gene mutational profiles were predominant in patients who had received at least three protease inhibitors. Knowing the amount and type of existing drug-induced mutations prior to initiation of the salvage therapy is useful for designing an appropriate salvage regimen. Although the database currently correlates sequences with treatment history, the plan is to expand the project to also correlate sequences with lab tests indicating susceptibility and clinical outcome. In the third step of the process, researchers test the activity of both approved and experimental antiretrovirals and try to correlate the results with specific mutations. Cross-resistance affected new compounds in clinical development, too.