Pre‐exposure prophylaxis: where are we in Europe?

Despite major advances in HIV therapy, the number of new HIV infections remains very high, even in high‐income countries where resurgence among men who have sex with men (MSM) has been witnessed. New prevention strategies have therefore to be assessed in order to curb the incidence of HIV infection. Recent studies have explored the effectiveness of antiretroviral therapy (ART) for HIV prevention and have generally yielded encouraging results. ART has been used successfully to prevent mother‐to‐child transmission of HIV, HIV acquisition following occupational or sexual exposure to HIV (post‐exposure prophylaxis), and more recently, to reduce the risk of HIV transmission within a serodiscordant couple by treating the HIV‐positive partner (HPTN 052 study). Another possible use of ART in prevention is pre‐exposure prophylaxis, where ART is taken by an HIV‐seronegative individual before HIV exposure. This PrEP strategy has been validated in animal models and more recently assessed in clinical trials in humans. The results of six large efficacy trials of PrEP are now available, but results have been inconsistent. The use of tenofovir gel in women at higher risk in Sub‐Saharan Africa has shown efficacy when given before and after sex in the Caprisa 004 study (reduction of 39% of the incidence of HIV), whereas no efficacy was shown with daily use in the VOICE trial. Similarly, daily oral PrEP with tenofovir or tenofovir and emtricitabine has proved effective in the Iprex trial in MSM (reduction of 42% of HIV incidence), in the Partners PrEP study (reduction of 67 to 75% in HIV incidence) and in the TDF‐2 trial (reduction of 63% in HIV incidence), but not in the Fem‐PrEP or the VOICE trials in women. There are many potential explanations for these apparently conflicting results, such as the populations in which these strategies have been assessed, the differential pharmacokinetics of ART in the male and female genital tracts and most likely the high level of adherence which is required to confer protection against HIV acquisition. These results have also generated a lot of controversy about the implementation of PrEP. Some think that the data are good enough to rollout PrEP in key populations at higher risk. Others think more research is needed before PrEP is implemented because of concerns around safety, emerging resistance, cost and change in sexual behaviour that might offset the benefit of PrEP. Safety is indeed a major concern in healthy individuals. New studies are underway to address these issues and are assessing PrEP regimens in open‐label studies (Iprex‐OLE in MSM), intermittent PrEP regimens to try to improve adherence, new ART classes and new modalities of drug delivery. PrEP is therefore a promising biomedical intervention that might be used in the near future in addition to current prevention methods to prevent HIV infection and help control the spread of this infection.