What if the most effective HIV prophylactic wasn’t pleasure-muting, giggle-inducing latex, but a pill you could take once a day—and prevent infection? That’s the idea behind pre-exposure prophylaxis, or “PREP,” a logical spinoff of PEP (post-exposure) that’s been in the works for years. But PREP has made even less progress than its equally controversial big brother, mainly because many preventionistas turn into Chicken Little when talk of condomless prevention comes up.

Now, after promising animal trials and an infusion of cash from the visionary Bill and Melinda Gates Foundation, the once-a-day nuke Viread (tenofovir) will be studied as PREP in humans. The participants, who will try the preparation as a pill and as a vaginal gel, are 1,600 sex workers worldwide, to be enrolled by the end of the year. (Sorry, guys: Testing in males isn’t on the drawing board yet.) 

The theory behind both PEP and PREP is simple: the HIV-killing drug gets inside the initial target cells and prevents HIV from replicating. Since tenofovir has low toxicity and causes few side effects, it’s the best available candidate for PREP, says study director Wade Cates, of Family Health International, the global health nonprofit. Controversial or not, if tenofovir proves effective, Gilead has promised to consider providing it free or at low cost in areas where the need for prevention is greatest.