HIV in Canada: A primer for service providers
Pre-exposure prophylaxis (PrEP)
- Pre-exposure prophylaxis (PrEP) is a highly effective strategy to reduce the risk of the sexual transmission of HIV
- PrEP involves the use of antiretroviral drugs starting before an HIV exposure and continuing throughout periods of high risk.
- PrEP works after HIV has made its way into the body. If this happens the medications in PrEP may prevent the virus from multiplying and spreading throughout the body.
The consistent and correct use of oral Truvada as pre-exposure prophylaxis (PrEP) is a highly effective strategy to reduce the risk of the sexual transmission of HIV. When this 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.
There are several factors important for maximizing its safety and effectiveness. PrEP:
- must only be used by people who are HIV negative
- must only be accessed through a healthcare provider
- requires that people are highly adherent to PrEP medications
- requires that people be tested for kidney function and 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.
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 for people at high risk for HIV. Truvada contains two anti-HIV drugs: tenofovir (also called TDF) and emtricitabine (also called FTC).
Daily oral PrEP is the only type of PrEP approved for use by Health Canada. It is the most commonly prescribed type of PrEP. There is strong evidence from multiple studies to support that it is a highly effective strategy to reduce the risk of the sexual transmission of HIV when used consistently and correctly. It has also been proven to be highly effective for both heterosexual and same-sex male serodiscordant couples.
For gay men and other men who have sex with men (MSM) only, there is an alternative form of PrEP called intermittent or ‘on-demand’ PrEP that can be considered for use. It consists of two pills taken two to 24 hours before first sexual activity, followed by one pill taken daily until 48 hours after the last sexual activity. This type of PrEP is not approved by Health Canada but can be prescribed ‘off-label’ by physicians. There is one study that supports on-demand PrEP as a highly effective strategy to reduce the risk of the sexual transmission of HIV when used consistently and correctly in MSM. On-demand PrEP is not recommended for heterosexual people.
Evidence from several randomized clinical trials has found that the use of daily oral PrEP significantly reduces the risk of HIV transmission. In these trials, PrEP was provided along with a comprehensive prevention package that included regular STI testing and treatment and ongoing adherence and risk-reduction counselling. Trials were conducted in several populations, including gay men and other 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 responsible for this wide range, as some participants were only taking their pills occasionally and others were not taking their pills at all. Indeed, adherence was so low in two studies that PrEP provided no protection against HIV infection.
Some studies have limited their analyses of effectiveness to participants who were taking their pills consistently. These analyses compared the risk of HIV infection among those with antiretroviral 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 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%. 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.
The daily use of oral Truvada as PrEP has been evaluated in “open-label” studies predominantly among MSM. 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.
The randomized clinical trials of daily oral PrEP that enrolled 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.
Evidence suggests that intermittent or “on demand” PrEP reduces the risk of HIV transmission among MSM. One randomly controlled trial (RCT), known as IPERGAY, evaluated the use of on-demand PrEP among MSM. In the IPERGAY trial, men were to take two pills at once two to 24 hours before first sexual activity, followed by one pill taken daily until 48 hours after the last sexual activity. The RCT phase of IPERGAY found an 86% reduced risk of HIV infection among gay men in the on-demand PrEP group compared to a placebo group (two participants in the PrEP arm became infected). Men in the RCT phase of this study had sex frequently and – as a result – took their pills on a regular basis (four pills a week on average). IPERGAY continued as an open-label extension with all participants offered on-demand PrEP. Results from the open-label phase showed that one HIV transmission occurred in 362 participants, over 515 person-years of follow-up. None of the three participants who became infected over the entire course of the study had PrEP detected in their blood, which means they were likely not adherent. On-demand PrEP has not been evaluated in populations other than gay men.
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 a man who was adherent to PrEP; 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, these tend to be mild, infrequent (affecting between 1% and 10% of users), and resolve after one to two months of use. 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, and the changes were reversible after stopping PrEP.
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 high risk of developing drug resistance. On the other hand, those who started PrEP when they were HIV negative, and became infected while taking it, hade a lower risk of developing drug resistance.
Based on studies that looked at participants who took their pills consistently, the consistent and correct use of oral 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.
Pre-exposure prophylaxis (PrEP) – CATIE fact sheet
Preexposure Prophylaxis for the Prevention of HIV in the United States: A Clinical Practice Guideline – U.S. Public Health Service
Preexposure Prophylaxis for the Prevention of HIV in the United States: Clinical Providers’ Supplement – U.S. Public Health Service
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