There were good reasons for researchers to choose Truvada as the first medication to study comprehensively as PrEP. First, there was good clinical experience with Truvada for HIV treatment. The two drugs in Truvada (tenofovir disoproxil fumarate and emtricitabine) were approved for HIV treatment in 2001 and 2003. With millions of patient-years of experience with these drugs, they were found to be safe and well tolerated. They can be taken over long periods of time (many years), without losing effectiveness. Truvada as PrEP would be an easy regimen to follow: one pill once a day, taken with or without food.
For these reasons, Truvada was selected for study as PrEP. It was found to be effective at preventing infection in non-human primate studies. Subsequently, in large randomized clinical trials, starting with the iPrEx trial, Truvada was found to be highly effective at reducing the risk of acquiring HIV and was found to be safe and well tolerated in HIV-negative individuals. As a result, in 2012, Truvada became the first medication to be approved as PrEP.
Descovy, another Gilead drug, was approved for treatment of HIV infection in 2016. Descovy is similar to Truvada but contains a different formulation of tenofovir. Subsequently, Gilead conducted a large-scale clinical trial to compare Truvada with Descovy to find out whether Descovy works as PrEP. This trial, called the DISCOVER trial, enrolled more than 5,000 cisgender men and transgender women and found that Descovy is "non-inferior to" (meaning it works just as well as) Truvada for PrEP. FDA approved Descovy for PrEP in October 2019.
Other medications are being studied for use as PrEP, and we expect that others will be approved for use in the future.