The use of daily Truvada pills as pre-exposure prophylaxis (PrEP) is a new HIV prevention strategy recently found to be effective in clinical trials. While generating a significant amount of excitement and hope, current use of PrEP in Canada is low and there are several unanswered questions about how this strategy can be safely and effectively implemented.
This article reviews the research on PrEP, what has happened to move this tool into practice, and the role front-line service providers can play in its safe and effective implementation in Canada.
PrEP refers to the ongoing use of anti-HIV drugs by an HIV-negative person in an effort to reduce their risk of becoming infected with HIV. It is a potential HIV prevention option during periods where a person is at "high risk" of HIV infection.
Many types of PrEP may be possible and are currently being researched, but only one type has been found effective in multiple clinical trials and approved by the Food and Drug Administration (FDA) in the United States. This form of PrEP involves taking a daily oral pill called Truvada (starting before a potential exposure to HIV and continuing afterwards). Truvada is a single pill that contains two anti-HIV drugs (tenofovir and emtricitabine). Tenofovir alone was also found to be effective in two PrEP clinical trials.
Before daily Truvada was found effective as PrEP, it was (and still is) commonly used in combination with other drugs for the treatment of HIV infection. Truvada is also used in combination with other drugs for preventing HIV after a high-risk exposure (post-exposure prophylaxis -- PEP).
While this article defines PrEP as the daily use of Truvada, it is important to note that other types of PrEP are being researched. For example, the IPERGAY study -- which has sites in Montreal and France -- is currently investigating the effectiveness of Truvada when taken on an intermittent basis (instead of daily).
More Than Taking a Pill a Day
The use of daily Truvada as PrEP is a tool for HIV-negative people at "high risk" of HIV infection. Therefore its use must be preceded with an HIV test and a risk assessment to determine if a person's level of risk makes them a good candidate (eligible) for PrEP.
Those who are eligible for PrEP, and decide to use it, also need to commit to regular medical appointments -- generally every three months. At each visit the client is monitored for side effects and toxicity, and tested for HIV (if a person tests HIV positive, their PrEP use must be discontinued) and sexually transmitted infections (STIs). PrEP does not protect against other STIs, such as gonorrhea, chlamydia, herpes and syphilis, and their presence may decrease the ability of PrEP to prevent HIV infection.
PrEP also needs to be combined with ongoing adherence support and additional HIV prevention services, such as risk-reduction counselling and access to condoms. Ongoing risk assessments are important to determine if a PrEP user is still at "high risk" and eligible for PrEP.
It Works ... When Taken
Several randomized placebo-controlled trials have investigated the effectiveness of daily Truvada as PrEP. These trials show that PrEP can reduce the risk of HIV infection when used by several different populations, including gay men and other men who have sex with men (MSM), transgender women who have sex with men, people who use injection drugs, and heterosexual men and women.
The overall effectiveness of PrEP in these trials has ranged widely; from 0 to 75%.1-6 The general consensus among researchers is that the varying levels of adherence to 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.7
For example, a study known as iPrEX found PrEP to be 44% effective overall but further investigation found that only half of the study participants had anti-HIV drugs in their blood, suggesting that many were not taking their pills consistently.1 Therefore, this 44% effectiveness is an underestimate of the effectiveness of PrEP when taken consistently. Adherence was so low in two other trials that PrEP was not found to be any more effective than a placebo pill at reducing the risk of HIV infection.3,6,7
It is unclear how much PrEP can reduce the risk of HIV infection when used consistently. In the iPrEX study, participants who were randomized to take PrEP and self-reported greater than 90% adherence to daily pill taking were 73% less likely to become infected with HIV compared to participants who were randomized to take a placebo pill and also reported high adherence.
Some studies have limited their analyses to participants randomized to take PrEP (and ignored participants randomized to take a placebo pill). These studies 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. Promisingly, these analyses suggest that the consistent use of PrEP may be able to reduce the risk of HIV infection by over 90%.1,2,8
However, since these analyses only looked at those who were assigned to take PrEP and randomization was not used to determine who had drug levels in their blood and who did not, their findings are observational (not protected by randomization). In general, observational evidence is considered to be less strong than randomized evidence because other factors, which are unaccounted for, may partly explain their findings.
Although the research on PrEP effectiveness can be difficult to interpret, the bottom line is that PrEP works and it works better when taken consistently.