Authors: Darrell Tan (University of Toronto, Canada)
Take a look behind the scenes of a recent Future Virology paper, entitled: ‘PrEParing for the Unexpected: Mechanisms and management of HIV Pre-Exposure Prophylaxis failure’, as we ask author Darrell Tan about the potential of pre-exposure prophylaxis (PrEP) for HIV prevention, PrEP failure and what research is needed in the field.
What inspired you to write this review?
PrEP is an extremely effective new tool for preventing HIV infection. Expanding the rollout of PrEP is thus an urgent priority worldwide to limit the onward transmission of HIV infection. In Toronto, we described the first well-documented case of PrEP failure despite complete adherence to the medication in 2016, and there have subsequently been a small number of additional cases of breakthrough infection.
As more people start using PrEP, and as more clinicians become involved in PrEP delivery, it will be increasingly important for all stakeholders to be aware of the very rare situations in which PrEP can fail.
Is HIV PrEP an effective tool for HIV prevention?
It is an extremely safe and effective strategy for preventing HIV infections. Among gay, bisexual and other men who have sex with men, for example, PrEP has been shown to decrease the risk of acquiring HIV by almost 100% if adherence is high.
What are the main reasons for PrEP failure?
The most common reason that PrEP fails is inadequate adherence. Just like any other medication, doses need to be taken regularly, according to the prescribed schedule, in order for it to work.
However, there are very rare situations in which a person who is taking PrEP regularly can still unfortunately acquire HIV, either because they are exposed to a drug-resistant virus, or due to other, less well-understood factors that somehow overcome the usual, excellent efficacy of PrEP.
Finally, if a person starts taking PrEP without knowing that they are already infected with HIV, then PrEP may appear to fail because evidence of infection will emerge during routine follow-up. For this latter reason it is imperative that people starting PrEP be carefully screened for unrecognized HIV infection using appropriate clinical evaluation and laboratory testing.
Is PrEP failure always preventable?
Mostly, by adhering consistently to the recommended dosing schedule, and by participating in regular follow-up that includes clinical and laboratory screening for HIV infection. However, in very rare circumstances PrEP may fail due to factors beyond the individual user’s control, such as encountering a PrEP-resistant virus.
What work are you hoping to do/what research do you think needs to be done in this area?
Surveillance is needed about the prevalence of circulating PrEP-resistant virus as PrEP use increases. Clinical data are also needed to better characterize the evolution of HIV diagnostic test results over time in the rare circumstances where a person seroconverts while using PrEP. Finally, interventions are needed to help support PrEP users in adhering with their medication.
You can find out more about Darrell’s work at his lab website: www.optionslab.ca
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