All you need to know about PrEP
What is PrEP?
Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy that uses antiretroviral drugs to protect HIVnegative people from HIV infection. People take antiretrovirals (ARVs) when they are at risk of exposure to HIV, in order to lower their risk of infection. PrEP is highly effective in preventing the sexual transmission of HIV, as long as the drugs are taken regularly, as directed. However, PrEP does not prevent other sexually transmitted infections or pregnancy.
What drug does PrEP contain?
Currently, people take PrEP as a pill which contains two drugs: tenofovir disoproxil fumarate and emtricitabine. Several different companies produce this pill, under different brand names. The original, patented version is called Truvada and is manufactured by Gilead. Other brand names for PrEP include Ricovir-EM (produced by Mylan), Tenvir-EM (Cipla) and Teno-EM (GPO). These are generic medicines which are much cheaper than Truvada but contain exactly the same active ingredients.
What does PrEP do?
The principle of PrEP is similar to that of antimalarial tablets used to prevent malaria when travelling in tropical countries. PrEP works in the following way. A person who does not have HIV takes enough antiretrovirals for there to be high levels of the drugs in their bloodstream, genital tract and rectum before any exposure to HIV. If exposure occurs, the ARVs stop the virus from entering cells and replicating. This prevents HIV from establishing itself and the person remains HIV negative.
Who is PrEP for?
National and international guidelines generally recommend that PrEP users should be HIV-negative, with no suspicion of acute (recent) HIV infection, be at substantial risk of HIV infection, have no medical reasons why they should not take PrEP drugs (such as kidney problems) and be willing to use PrEP as prescribed, including regular HIV testing. The question of who is considered to be at sufficiently substantial risk of HIV infection for public health agencies to recommend PrEP depends on the characteristics of the HIV epidemic in a particular place. The World Health Organization defines substantial risk of HIV in terms of an incidence of 3% or more. In other words, that in a particular group of people, at least 3 in 100 people would become HIV positive each year, if PrEP was not provided.
Why take PrEP?
The risk of acquiring HIV is higher for people who come from countries with a high prevalence of HIV (e.g. subSaharan Africa, south east Asia) and for their sexual partners. It is also higher for people travelling to those countries and having sex with people they meet there. Guidelines therefore often refer to these kinds of factors to identify cisgender heterosexual men and women considered to be at substantial risk of HIV infection. Nonetheless, individuals often have a clearer understanding of whether they need PrEP than their doctors. The World Health Organization's PrEP implementation tool suggests that if someone requests PrEP, this is an indication that they are likely to be at substantial risk of HIV. People asking for PrEP are likely to have made this choice based on a careful assessment of their personal circumstances, risk and desire for additional HIV prevention. Clinicians should consider any request for PrEP seriously, the World Health Organisation.
How to take PrEP
For people whose HIV risk is through vaginal sex or injecting drug use, PrEP needs to be taken daily. For people whose risk is through anal sex, there are two additional options: four-days-a-week and on-demand dosing.
DAILY DOSING This involves taking PrEP once a day, every day, on an ongoing basis. Most PrEP studies were based on daily dosing, so there is more scientific evidence for daily dosing than other approaches. Daily dosing has been tested in relation to anal sex, vaginal sex (with cisgender people) and injecting drug use. Many international guidelines recommend daily dosing as the only way to take PrEP.
FOUR DAYS A WEEK Studies suggest that for people whose HIV risk is through anal sex, taking PrEP four days a week is highly effective (see question 19). This hasn't been tested in the most rigorous kind of study (a randomised controlled trial), but the experience so far suggests that this approach is effective. Some people may decide to take just four doses a week, out of concern about cost or side-effects. In this case, it is best to take PrEP on alternate days, for example on Tuesdays, Thursdays, Saturdays and Sundays. Due to differences in drug absorption in different parts of the body, this is unlikely to work when the HIV risk is through vaginal sex or injecting drug use.
ON-DEMAND DOSING This approach, also known as 'event-driven' or 'event based' dosing, involves taking PrEP just before and after having sex. The French IPERGAY study showed that on-demand dosing is very effective in preventing transmission through anal sex. The on-demand IPERGAY regimen involves taking a double dose of PrEP (two pills) from 2-24 hours before anticipated sex, and then, if sex happens, additional pills 24 hours and 48 hours after the double dose. In the event of sex on several days in a row, one pill should be taken each day until 48 hours after the last sexual intercourse. Most European guidelines support on-demand dosing for people whose HIV risk is through anal sex. There is more information on its effectiveness in question 13. The UK guide to PrEP, published by HIV i-Base, gives practical examples of how this regimen can be used. Due to differences in drug absorption in different parts of the body, on-demand dosing is not recommended for people whose HIV risk is through vaginal sex or injecting drug use.
How PrEP works
The research to answer this question comes from lab studies which show how long it takes for a maximum concentration or 'steady state' of drug to be reached in blood, vaginal tissues and rectal tissues. Drugs vary in how long they take to achieve this concentration in different parts of the body. For example, there are differences between the two drugs contained in PrEP, tenofovir and emtricitabine, although both are probably needed for PrEP to be effective. The research is complex but incomplete (see the next question for more details). After reviewing it, the authors of [draft] BHIVA guidelines make the following recommendations for practical advice to give to PrEP users. There are different recommendations for people whose risk is through anal or vaginal sex.
For people whose risk of HIV is through anal sex, whatever dosing schedule they use: Starting: PrEP can be started with a double dose (two pills) taken 2–24 hours before sex. Stopping: PrEP should be continued daily until 48 hours after the last sexual risk. Re-starting: If PrEP has been stopped and it is less than 7 days since the last dose then PrEP can be restarted with a single dose. If it has been more than 7 days, take a double dose.
For people whose risk of HIV is through vaginal sex or frontal sex: Starting: PrEP should be started as a daily regimen of one pill a day, 7 days ahead of the likely sexual risk. If it is not possible to take PrEP for a full 7 days before a likely sexual risk, starting with a double dose (two pills) might provide some extra protection, but this is unproven.
Condoms and other prevention strategies could also be used during the first few days of PrEP use. Stopping: PrEP should be continued daily until 7 days after the last sexual risk. Re-starting: The same guidance as for starting.
People who are at risk through injecting drug use (slamming) as well as sexual risk need to know that PrEP takes longer to achieve protective concentrations in the blood than in tissues. Taking PrEP for 7 days before and 7 days after is recommended.
Adherence in order for PrEP to work
By testing participants' blood for the presence of PrEP drugs, researchers have attempted to estimate the number of PrEP doses they have actually taken. They have then looked at the number of HIV infections in people with different levels of adherence. The useful studies which have taken this approach have all been with MSM, where the HIV risk is through anal sex.
Nonetheless, for people whose risk is through anal sex, it may be reassuring to know that four or more doses a week appears to be highly effective. Due to differences in drug absorption in different body tissues, it is thought that higher levels of adherence are required when the HIV risk is through vaginal sex – probably six or seven doses a week.