The 40-year-old – who has not appeared in a movie since 2009 – will replace Gael Garcia Bernal in the new film from the director of Café de Flore.
The 30 Seconds to Mars frontman will star alongside Jennifer Garner and Matthew McConaughey in the AIDS drama, report Deadline.
The picture – based on the true story of Ron Woodruff – follows an electrician who is diagnosed with the disease in 1986 and told he has six months to live.
In a bid to extend his life, Woodruff began experimenting with underground, illegal drugs that successfully extended his timespan.
Woodruff began distributing the drugs into the hands of other AIDS sufferers, before the FDA tried to shut him down and keep the drugs out of the country.
Leto – who will play a cross-dressing HIV-positive man who helps the lead character – has had roles in Darren Aronofsky’s Requiem For A Dream, David Fincher’s Fight Club and Panic Room, and was last seen in Jaco Van Dormael’s Mr. Nobody.
