A once daily pill reduces risk in some groups but implementation will be challenging On 16 July 2012, the US Food and Drug Administration (FDA) approved a fixed dose combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC; Truvada) as a once daily pill for prevention of HIV infection in at risk adults.1 Approval of this combination for pre-exposure prophylaxis is one of several reasons why some HIV experts believe “the end of AIDS” is in sight.2 But is such optimism justified? The excitement about this treatment is understandable given that the HIV epidemic in the United States persists,1 mainly among men who have sex with men and African-Americans. Condoms are effective at preventing HIV,3 but their use is inconsistent.1 Identifying and treating every infected person to achieve viral suppression could reduce transmission (so called treatment as prevention),4 but such treatment expansion is still a long way off. Therefore, pre-exposure prophylaxis could, in theory, produce population level reductions in HIV transmission. The efficacy of TDF-FTC for pre-exposure prophylaxis was demonstrated in two large randomised double blind placebo controlled trials, which were the basis for its approval by the FDA. The multinational Pre-exposure Prophylaxis Initiative trial, which looked at 2499 HIV negative men or transgender women who have sex with men who reported high risk behaviour, found a 44% reduction in incidence (95% confidence interval 15% to 63%; P=0.005).5 A pre-exposure prophylaxis trial in Kenya and Uganda of 4758 HIV serodiscordant heterosexual couples found …