Use of antiretroviral drugs to prevent sexual transmission of HIV-1 has been a critical priority since their development. In the past 2 years results from seven important prevention trials have been reported (table). One of the trials, HPTN 052, 1 showed nearly complete prevention of HIV transmission when viraemia was suppressed. The other studies focused on antiretroviral agents for pre-exposure prophylaxis: two used 1% tenofovir gel (CAPRISA 0042 and VOICE3), four used oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in combination (iPrEX, 4 TDF2, 5 Partners in Prevention [PIP], 6 and Fem-PrEP7), and two used oral TDF alone (VOICE3 and PIP6). Somewhat confusingly, the findings of these studies have led to reports both of successful prevention of HIV infection (CAPRISA 004, 2 iPrEx, 4 TDF2, 5 and PIP6) and of futility (VOICE3 and Fem-PrEP7).

Clearly, results on pre-exposure prophylaxis will be used to inform policy and to plan future research, and so the trials’ findings need to be considered carefully. There were key differences in the pre-exposure prophylaxis trials (table): each included different populations with distinct routes of HIV transmission. For example, iPrEx4 was the first success for oral pre-exposure prophylaxis and focused on men who have sex with men. It is reasonable to assume that anal intercourse was the key route of transmission in the iPrEx trial, 4 and was less frequently the source of HIV infection in the heterosexual women and men in the Fem-PrEP, 7 VOICE, 3 TDF2, 5 and PIP6 studies. HIV acquisition is more efficient after anal intercourse, 8 and more HIV variants are acquired during anal intercourse than cervicovaginal exposure. 9 We have reported substantial differences in antiretroviral drug concen trations in mucosal tissues. 10–12