What is the evidence for PrEP (Pre-Exposure Prophylaxis)?

Bottle of Truvada
SAN ANSELMO, CA - NOVEMBER 23: Bottles of antiretroviral drug Truvada are displayed at Jack's Pharmacy on November 23, 2010 in San Anselmo, California. A study published by the New England Journal of Medicine showed that men who took the daily antiretroviral pill Truvada significantly reduced their risk of contracting HIV. (Photo Illustration by Justin Sullivan/Getty Images). Justin Sullivan/Getty Images News/Getty Images

Pre-exposure prophylaxis, otherwise known as PrEP, is the practice of giving high-risk individuals antiretroviral medication in order to reduce their risk of acquiring HIV. PrEP is primarily recommended for use by people who have a high probability of sexual exposure to HIV. It has been shown to be effective at helping people in serodiscordant couples reduce their risk of being infected by their partners.

It's also been shown to reduce the risk of HIV in men who have sex with men.

PrEP has not yet been thoroughly evaluated for people who are regularly exposed to HIV through means other than sexual activity, such as injection drug use. However, as there has been at least one successful study of PrEP in injection drug users,  the CDC currently recommends that providers who are working with drug users consider whether PrEP might be an appropriate means of HIV prevention for those who are at very high risk of acquiring HIV.

What is the Evidence for PrEP?

By the start of the year 2015, there had been more than a dozen trials examining the efficacy of PrEP in protecting high-risk individuals against HIV infection. They have consistently shown that use of PrEP significantly reduces the incidence of new HIV infections, particularly for people who take the drugs reliably. Evidence clearly supports the use of PrEP to reduce sexual transmission of HIV in both high risk men who have sex with men and in high risk heterosexual couples.

How Does PrEP Work?

When people are given PrEP, they are using the same medication that individuals who are infected with HIV take to keep their infections under control. Although the specific way that taking such medication can prevent infection has not yet been clarified, it is likely that having the medication in the bloodstream makes it difficult for any early infection to take hold and establish itself.

In other words, the medication doesn't stop HIV from entering the body. Instead, it seems to make it more difficult for it to turn into a lasting infection.

So far, the most significant problem identified for PrEP use is that it is difficult for people to remain adherent to the prescription regimen, particularly when they don't see themselves as at risk. Since good adherence is associated with better protection against infection, that is potentially a real concern. Some scientists are investigating different PrEP delivery methods, such as long-term injections, that might be able to make it easier for people to take their medication correctly.

Are There Any Dangers of Using PrEP?

There are several potential downsides of using PrEP. First, there is a small risk of side effects from the medication that is used for treatment, although a meta-analysis of the PrEP trials showed no increase in serious adverse events in the treatment groups when compared to the control groups.  However, people taking PrEP instead of a placebo were more likely to experience nausea and vomiting, and in some studies they also experienced changes to their liver and kidney function that were reversible when they stopped taking the drugs.

Other than side effects from the medication, the main thing researchers are worried about in people using PrEP, particularly if it is not used consistently, is their becoming infected with a strain of drug-resistant HIV that can't be treated with the PrEP medication. Fortunately, research to date suggests that resistance mutations caused by PrEP are quite rare and do not usually cause significant problems after people have stopped taking PrEP. As resistance also seems to be more common in people who start on PrEP when they already have an unrecognized acute HIV infection, it is a good idea for doctors to carefully assess whether there is any chance people might be infected before starting PrEP.

Some individuals also have concerns about the ethics of treating people who aren't infected with HIV when so many people around the world who are infected have difficulty accessing medication. In addition, many health educators (including myself) have been concerned about the possibility of risk compensation in PrEP users. However, to date, studies have not shown that people have riskier sex when they start using PrEP. Those inclined to practice safe sex still do so, and those who aren't wouldn't use condoms anyway. In fact, some professionals think that offering people a choice of prevention techniques might actually make them more likely to take steps to reduce their risk, because talking about PrEP and other options can make the possibility of HIV infection seem more immediate.

Clarifying The Difference Between PEP and PrEP

Post-exposure prophylaxis, or PEP, is an entirely different type of prevention than PrEP. It is used for people who have a known exposure to HIV, most often after exposure to infected blood in a workplace environment, although it can also be given to people who have had risky sex with an infected person. When someone receives PEP, they are given antiretroviral medication for approximately one month after the exposure occurred, and then treatment is stopped. In contrast, PrEP may be used indefinitely by people who believe there is a possibility they could be exposed to the virus at some point in the future.

Condoms Are Still Part of Being PrEPared

PrEP works pretty well at preventing sexual transmission of HIV in people who use it correctly and consistently. However, it's still not as effective or convenient as condoms and other barrier methods, which prevent exposure to potentially infectious bodily fluids. That, along with the risk of being exposed to other STDs, is a reason why it's still a good idea for people using PrEP to practice safer sex, whenever it is practical to do so. For that matter, it's also be a good idea for people at high risk who use condoms consistently to consider adding PrEP.

Sources:

Centers for Disease Control and Prevention (CDC). Update to Interim Guidance for Preexposure Prophylaxis (PrEP) for the Prevention of HIV Infection: PrEP for injecting drug users. MMWR Morb Mortal Wkly Rep. 2013 Jun 14;62(23):463-5

Corneli A, Wang M, Agot K, Ahmed K, Lombaard J, Van Damme L; FEM-PrEP Study Group. Perception of HIV risk and adherence to a daily, investigational pill for HIV prevention in FEM-PrEP. J Acquir Immune Defic Syndr. 2014 Dec 15;67(5):555-63. doi: 10.1097/QAI.0000000000000362.

Escudero DJ, Lurie MN, Kerr T, Howe CJ, Marshall BD. HIV pre-exposure prophylaxis for people who inject drugs: a review of current results and an agenda for future research. J Int AIDS Soc. 2014 Mar 27;17:18899. doi:10.7448/IAS.17.1.18899.

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Krakower DS, Mayer KH. Pre-Exposure Prophylaxis to Prevent HIV Infection: Current Status, Future Opportunities and Challenges. Drugs. 2015 Feb;75(3):243-51. doi: 10.1007/s40265-015-0355-4.

Liegler T, Abdel-Mohsen M, Bentley LG, Atchison R, Schmidt T, Javier J, Mehrotra M, Eden C, Glidden DV, McMahan V, Anderson PL, Li P, Wong JK, Buchbinder S, Guanira JV, Grant RM; iPrEx Study Team. HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial. J Infect Dis. 2014 Oct 15;210(8):1217-27. doi:10.1093/infdis/jiu233.

Marcus JL, Glidden DV, Mayer KH, Liu AY, Buchbinder SP, Amico KR, McMahan V, Kallas EG, Montoya-Herrera O, Pilotto J, Grant RM. No evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis. PLoS One. 2013 Dec 18;8(12):e81997. doi: 10.1371/journal.pone.0081997.

Okwundu CI, Uthman OA, Okoromah CA. Antiretroviral pre-exposure prophylaxis(PrEP) for preventing HIV in high-risk individuals. Cochrane Database Syst Rev.2012 Jul 11;7:CD007189. doi: 10.1002/14651858.CD007189.pub3.

Smith DK, Herbst JH, Rose CE. Estimating HIV protective effects of method adherence with combinations of preexposure prophylaxis and condom use among African American men who have sex with men. Sex Transm Dis. 2015 Feb;42(2):88-92. doi: 10.1097/OLQ.0000000000000238.

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