How PrEP might be used

Pre- and post-exposure prophylaxis are not mutually exclusive. There is likely to be a window of opportunity for some time before or after exposure in which ARV drugs could prevent infection. Indeed, some animal studies indicate that combining pre- and post-exposure ARV doses may be more effective than a single pre-exposure dose, and in a couple of ongoing PrEP studies the trial regimen consists of one dose in advance of sex and another after – the same regimen as in the CAPRISA 004 trial of a topical microbicide.

Taking a single post-exposure dose is not the same as post-exposure prophylaxis, however. The main difference between PrEP and PEP is the envisaged pattern of use. PEP is already available in many countries as a course of drugs, an emergency measure designed to be provided occasionally to individuals who have just had a very high-risk exposure to HIV. It generally consists of four weeks’ worth of ARV triple-combination therapy. PrEP, at least as studied in current efficacy trials, consists of the daily, or at least routine, use of one or two ARV drugs, and is envisaged as a broader public health intervention, albeit one offered to specific populations at very high risk of HIV.

Daily dosing may not realistically reflect how people will eventually take PrEP. One of the unanswered research questions around PrEP is whether it will work if taken on an ad hoc or occasional basis. Adherence questions apart, PrEP appears to require quite high systemic levels of drug in the body in order to work, and it is not known if these will be achieved through occasional use. A study involving a monthly injection of a long-lasting formulation of one HIV drug is planned to circumvent some of these problems.

Until recently, there was also an obvious distinction between PrEP and microbicides in terms of timing of use. Microbicides might be described as peri­-exposure prophylaxis (prevention at the time of exposure), in that initially it was envisaged that they would be used during the time of exposure to HIV and would be applied shortly before sex.

With long-lasting microbicide formulations like vaginal rings now being developed, there is a less distinct difference between PrEP, PEP and microbicides in terms of timing of doses. Some researchers have preferred terms like ‘topical PrEP’ for microbicides for several years. At least one trial is directly comparing oral PrEP with a microbicide gel, and there is no reason, other than expense, why the two strategies could not be used together. Similarly, PrEP has been dubbed ‘oral ARV prophylaxis’.

Others, such as the virology and resistance expert John Mellors,¹ are using the even broader terms ‘antiretroviral-based therapy’ (ART) and ‘antiretroviral-based prevention’ (ARP) to make it clear that proposed prevention strategies like ‘universal test and treat’ (UTT) for HIV-positive people and PrEP for HIV-negative people are broadly similar in their application and mode of action.