CATIE statement on the use of pre-exposure prophylaxis (PrEP) to prevent the sexual transmission of HIV

Over the past several years the HIV prevention toolbox has expanded significantly. This is due to a rapid growth in our knowledge of effective approaches that help prevent the transmission of HIV. However, to maximize the impact on the HIV epidemic, we must effectively increase awareness, uptake and proper use of these approaches.

The CATIE statements summarize the best available evidence on the effectiveness of three approaches to help prevent the sexual transmission of HIV. These statements were developed to help service providers in Canada adapt their programs and incorporate this evidence into their messaging.

There are three highly effective strategies to reduce the risk of the sexual transmission of HIV:

Highly effective strategies can reduce the risk of HIV transmission by 90% or more.

The following statement focuses on PrEP. A simple key message is followed by recommendations for service providers and a list of available tools and resources. A review of the evidence is also provided that service providers can use for more specific discussions around risk according to clients’ needs. Please consult the companion statements for more information on the other two highly effective strategies.

Key Message

The consistent and correct use of daily oral Truvada as pre-exposure prophylaxis (PrEP) is a highly effective strategy to reduce the risk of the sexual transmission of HIV. When a highly effective strategy is used consistently and correctly as part of a comprehensive plan for sexual health, it is rare for HIV to be transmitted.

For more information, please see the evidence review at the end of this statement. 

Recommendations for service providers

PrEP is no longer a strategy on the horizon but one that is currently available and being used in Canada. In February 2016, Health Canada approved the use of daily oral Truvada for PrEP in combination with safer sex practices to reduce the risk of the sexual transmission of HIV. Truvada contains two anti-HIV drugs: tenofovir (also called TDF) and emtricitabine (also called FTC).

People working in HIV prevention have an important role to play in promoting PrEP as a highly effective prevention strategy.

Below are recommendations on how you might better integrate PrEP into your practice.

1. Improve awareness of PrEP as a highly effective HIV prevention strategy, including the factors important for maximizing its effectiveness. Any educational and counselling activities provided for HIV-negative clients and for HIV-positive clients who have HIV-negative partners should include information on the prevention benefits of PrEP and how to use it correctly.

PrEP should only be used by people who are HIV negative and at high risk for HIV infection. The Truvada product monograph lists the following factors that may help to identify clients who are at high risk:

  • “has partner(s) known to be HIV-1 infected, or
  • engages in sexual activity within a high prevalence area or social network and one or more of the following:
    • inconsistent or no condom use
    • diagnosis of sexually transmitted infections
    • exchange of sex for commodities (such as money, food, shelter, or drugs)
    • use of illicit drugs or alcohol dependence
    • incarceration
    • partner(s) of unknown HIV-1 status with any of the factors listed above”

Therefore education and counselling activities should include a discussion of a client’s level of HIV risk so that they can make an informed decision about whether PrEP is right for them.

Education and counselling activities should also include discussion of other prevention strategies such as, but not limited to, condoms and the use of antiretroviral treatment (ART) as prevention. Encourage clients to choose the combination of strategies that will work most effectively for them.

Inform clients who are interested in PrEP of the factors important for maximizing its safety and effectiveness. Emphasize that PrEP:

  • must only be used by people who are HIV negative
  • must only be accessed through a healthcare provider
  • requires the daily use of a pill called Truvada
  • requires that people be screened for the hepatitis B virus before taking Truvada
  • requires regular clinic visits with a healthcare provider every three months to test for HIV and sexually transmitted infections (STIs), to monitor for side effects and toxicity, and for adherence and risk-reduction counselling.

Your clients should know that PrEP can be much less effective against HIV infection when doses of the medication are missed. They should also know that it is important to attend their regular medical appointments while taking PrEP.

You can also lead or support efforts to improve awareness of PrEP among a range of service providers in your area, including doctors, nurses, pharmacists, and non-clinical staff at community-based organizations.

2. Facilitate and support appropriate uptake and use of PrEP as a prevention strategy. Guidelines recommend the offer of PrEP to individuals at high risk for HIV infection as part of a comprehensive prevention package that includes regular STI testing and ongoing adherence and risk-reduction counselling. PrEP is not for everyone and you can support clients to decide whether PrEP is right for them. During discussions, help your clients consider their level of HIV risk, and the possible side effects, as well as their ability to cover the cost (i.e., insurance coverage), access a knowledgeable healthcare provider, and adhere to a daily pill-taking regimen and regular medical visits.

Whenever possible, be aware of – and develop partnerships with – local healthcare providers, clinics, and health centres that are willing to prescribe PrEP. Establishing these connections with other service providers can ensure that clients who may benefit from PrEP (and are interested in using it) are linked to a location where it is available. Clients may need support in talking to a healthcare provider about PrEP and determining whether their provincial/territorial or private health insurance will cover the cost of the medications. Clients who start PrEP should also be supported with the consistent and correct use of this strategy. You may have to offer, or link clients to, interventions and services to support medication adherence and continued engagement in medical care.

3. Encourage a comprehensive plan for sexual health. Discuss how PrEP fits into a comprehensive plan for sexual health. When used consistently and correctly, PrEP is a highly effective strategy to reduce the risk of sexual transmission of HIV. However, it does not eliminate the risk. We know that adherence to daily medications can be an issue for many people and that this decreases the effectiveness of PrEP. We also know that, while the risk for HIV transmission is quite low from a single exposure, the risk for HIV transmission increases over multiple exposures to HIV. This means that the more someone participates in a behaviour that poses a risk for HIV transmission the greater their risk of getting HIV. Finally, we also know that PrEP does not protect against STIs or some drug-resistant strains of HIV. It’s important that clients know these risks so they can make an informed decision about combining PrEP with other risk-reduction strategies to help minimize their HIV and STI risk over the long term.

4. Address underlying risk of HIV transmission. HIV prevention counselling offers an opportunity to engage individuals at risk for acquiring or transmitting HIV in additional services. You can help your clients address the underlying factors that may increase their risk for acquiring and transmitting HIV, such as depression or alcohol and other substance use; reinforce safer sex strategies; and facilitate the increased use of all appropriate prevention strategies. You may find that risk-reduction counselling alone is not enough. You may need to provide – or link clients to – appropriate and relevant support services.

5. Offer comprehensive couples-based counselling. For couples, you may want to offer to counsel both partners in the relationship at the same time (couples-based counselling) as this may be more effective than counselling partners individually. Couples-based counselling can create a supportive space where clients can come to a consensual agreement on how to reduce their risk of HIV transmission, develop ways to support each other in using HIV prevention strategies consistently and correctly, and discuss potentially sensitive issues relevant to HIV prevention. Be prepared to discuss issues such as: what a couple wants from sex and the type of sex they enjoy most; the desire for pleasure, intimacy, conception, and monogamy or non-monogamy; and disclosure of sex outside the relationship. This counselling can also support non-monogamous clients to develop strategies or agreements to reduce the risk of acquiring HIV or STIs from outside partners, such as the consistent and correct use of condoms when having sex outside the relationship.

6. Incorporate information about PrEP into all prevention programming to increase its impact. In-person counselling is one way to convey information about PrEP as a highly effective prevention strategy. However, this information can be integrated into a variety of other communication channels, such as print publications, websites and campaigns to increase its reach and impact.

Tools and Resources

CATIE resources

Pre-exposure prophylaxis (PrEP) – Fact sheet

Truvada – Fact sheet

Condoms, PrEP, and the use of antiretroviral treatment to prevent HIV – webinar

Truvada approved for HIV prevention in Canada – CATIE News

Use of daily Truvada as PrEP is highly effective for gay men in PROUD demonstration project – CATIE News

PrEP use in the “real world”: Results from the iPrEX open label extension – CATIE News

“On-demand” PrEP strategy highly effective for gay men who have frequent sex – CATIE News

A case of HIV transmission on PrEP and its implications – CATIE News

Uptake of PrEP in the United StatesCATIE News

Two North American surveys engage doctors about their attitudes towards PrEPCATIE News

Guidelines

Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations – World Health Organization

Oral pre-exposure prophylaxis–putting a new choice in context – UNAIDS

PrEP for the prevention of HIV infection in the United States: A clinical practice guideline – US Centers for Disease Control and Prevention (CDC)

Clinical providers’ supplement for providing PrEP – CDC

Interim guidance on providing HIV PrEP – Quebec Ministry of Health (French only)

Pre-exposure prophylaxis (PrEP) guidelines – B.C. Centre for Excellence in HIV/AIDS

Other resources

Truvada Product Monograph – Gilead Sciences

Ongoing and planned PrEP evaluation studies – AVAC

Len Tooley on PrEP – PositiveLite.com

PrEP pops up on cruising sites – PositiveLite.com

PrEP – Is this just a phase I am going through? – My PrEP Experience

Evidence

The use of daily oral Truvada is the only type of PrEP that has been found to be effective in multiple studies, approved by Health Canada, and recommended by the World Health Organization (WHO) and Centers for Disease Control (CDC).

The use of daily oral PrEP has been evaluated in several randomized clinical trials.1–7 These trials have found that the use of daily PrEP as part of a comprehensive prevention package that includes regular STI testing and treatment and ongoing adherence and risk-reduction counselling can reduce the risk of HIV infection for several populations, including gay men and other men who have sex with men (MSM), heterosexual men and women, and people who use injection drugs. The overall reduction in HIV risk provided by PrEP in these studies ranged from zero to 86%. Varying levels of adherence to daily pill-taking among study participants is generally thought to be responsible for this wide range, as some participants were only taking their pills occasionally and others were not taking their pills at all.8 Indeed, adherence was so low in two studies that PrEP provided no protection against HIV infection.3,6

Some studies have limited their analyses of effectiveness to participants who were taking their pills consistently.1,2,5 These analyses compared the risk of HIV infection among those with anti-HIV drugs in their blood (which suggests they were using PrEP consistently) to those who did not have these drugs in their blood. These analyses show us that that the consistent use of PrEP can reduce the risk for the sexual transmission of HIV for gay men and other MSM and heterosexual men and women by between 85% and 92%.9 A modelling study has estimated that daily oral PrEP may be up to 99% effective at reducing the risk for the sexual transmission of HIV among MSM but this has not been demonstrated in a clinical trial.10

The daily use of oral Truvada as PrEP has been evaluated in “open-label” studies predominantly among MSM.7,11 In these types of studies, no placebo is used and participants using PrEP know that they are taking Truvada pills and that it is effective against HIV infection. Several of these "open-label" studies have been completed and they support the conclusion that the daily use of Truvada as PrEP is highly effective against HIV infection when used consistently and correctly. For example, one of these studies found that PrEP in the "real world" reduced the risk of HIV infection by 86% in MSM.7

The randomized clinical trials that enrolled both heterosexual men and women found no difference in the effectiveness of PrEP based on sex when used consistently and correctly. However, there is some evidence to suggest that Truvada reaches maximum drug concentrations more quickly in rectal tissues compared to vaginal tissues, and that drug levels are higher in rectal tissues. For this reason, women having vaginal sex may need to be more adherent to PrEP than men having anal sex to maintain sufficient drug levels to help prevent HIV infection.3, 12-17

Truvada as PrEP is not effective against strains of HIV that are resistant to Truvada. There has been one reported case of transmission of drug resistant HIV to someone who was adherent to PrEP.18 However this is a rare case.

PrEP appears to be generally safe and well tolerated. Although Truvada is associated with some side effects such as headache, nausea, diarrhea and fatigue, they tend to be mild, infrequent (affecting between 1% and 10% of users), and resolve after one to two months of use.1–6 The use of Truvada as PrEP has been associated with more concerning toxicities in a small number of people, such as small decreases in kidney, liver and bone health. Promisingly, these toxicities did not increase the risk of kidney or liver failure, or bone fracture. However, the long-term clinical significance remains unclear, as most studies only followed participants for an average of one to two years.

Of concern is the potential for the development of drug resistance in people who are taking Truvada as PrEP. If drug resistance develops, this could limit future treatment options. In clinical trials, those who started PrEP when they were already HIV positive (their infection was missed during initial screening for HIV because they were recently infected and in the “window period”) were at very high risk of developing drug resistance.1–6 On the other hand, those who started PrEP when they were HIV negative, and became infected while taking it, appeared to have a lower risk of developing drug resistance.

A randomized, placebo-controlled trial found that an intermittent, “on demand” PrEP strategy was effective at reducing the risk of HIV infection for gay men who had frequent sex.19 This strategy involved taking an initial dose of two Truvada pills between two and 24 hours before a sex act, then a single pill taken 24 hours after the initial dose, and finally a single pill taken 48 hours after the initial dose. If a person had sex again before completing this regimen, they were asked to take a pill every 24 hours while sexually active and then finish with a pill a day for the two days after their last sexual event. This strategy reduced the risk of HIV infection by 86%. However, men in the study reported having frequent sex and taking on average four pills per week. This frequent dosing may be important to maintain high levels of drug in the body. It is still unclear how well an intermittent PrEP strategy would work for gay men who have less frequent sex, or for other populations such as women or people who inject drugs.  

Intermittent PrEP is not currently recommended by the CDC or WHO guidelines but the European AIDS Clinical Society guidelines include its use for MSM who have frequent condomless sex.20 However, intermittent PrEP can be prescribed "off label" by physicians in Canada.

Based on studies that looked at participants who took their pills consistently, we conclude that the consistent and correct use of PrEP, when combined with a comprehensive sexual health plan that includes regular STI testing and treatment, HIV testing and ongoing adherence and risk-reduction counselling, is a highly effective strategy for reducing the risk of the sexual transmission of HIV.

References

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  2. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. New England Journal of Medicine. 2012;367(5):399–410.
  3. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. New England Journal of Medicine. 2012;367(5):411–422.
  4. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet. 2013;381(9883):2083–2090.
  5. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. New England Journal of Medicine 2012;367(5):423–434.
  6. Marrazzo J, Ramjee G, Richardson BA et al. Pre-exposure prophylaxis for HIV infection among African women. New England Journal of Medicine 2015; 372: 509-518.
  7. McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. The Lancet. 2016; 387 (10013): 53–60.
  8. Van der Straten A, Van Damme L, Haberer JE, Bangsberg DR. Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention. AIDS. 2012;26(7):F13–19.
  9. Spinner C; Boesecke C, Zink A,  et al. HIV pre-exposure prophylaxis (PrEP): a review of current knowledge or oral systemic HIV PrEP in humans. Infection. 2015 Oct 15:1–8.
  10. Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Science Translational Medicine. 2012;4(151):151ra125.
  11. Grant RM, Anderson PL, McMahan V, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infectious Diseases. 2014; 14(9):820–829.
  12. Patterson KB, Prince HA, Kraft E, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Science Translational Medicine. 2011;3(112):112re114.
  13. Anderson PL, Kiser JJ, Gardner EM, et al. Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection. Journal of Antimicrobial Chemotherapy. 2011;66(2):240-250.
  14. Anderson PL. Pharmacology considerations for HIV prevention. 13th International Workshop on Clinical Pharmacology of HIV, 2012.
  15. Cottrell ML, Srinivas N, Kashuba AD. Pharmacokinetics of antiretrovirals in mucosal tissue. Expert Opinion on Drug Metabolism and Toxicology. 2015; 11: 893–905.
  16. Cottrell MI YK, Prince Ha, Sykes C, et al. Predicting effective Truvada PrEP dosing strategies with a novel PK-PD model incorporating tissue active metabolites and endogenous nucleotides. HIV Research for Prevention (R4P), 2014.
  17. Landovitz RJ. PrEP for HIV Prevention: what we know and what we still need to know for implementation. Conference on Retroviruses and Opportunistic Infections (CROI), 2015.
  18. Knox DC, Tan DH, Harrigan PR, et al. HIV infection with multi-class resistance despite pre-exposure prophylaxis (PrEP). Conference on Retroviruses and Opportunistic Infections (CROI), 22-25 February, 2016. Abstract 169aLB.
  19. Molina J-M, Capitant C, Spire B, et al. On demand Preexposure Prophylaxis in Men at High risk for HIV-1 Infection. New England Journal of Medicine. 2015; 373(23):2237-2246.
  20. European AIDS Clinical Society (EACS). Guidelines Version 8.0, October 2015. Available at: http://www.eacsociety.org/files/guidelines_8_0-english_web.pdf