Q&A: What clinicians should know about starting, stopping and restarting PrEP
The need for HIV PrEP fluctuates as risk behaviors change. In a recent viewpoint published in The Lancet HIV, researchers reviewed current guidelines and the clinical implications of starting, stopping and restarting the daily medication.
Healio spoke with one of the authors, Sarah E. Rutstein, MD, an internal medicine specialist at the University of North Carolina, Chapel Hill, to discuss what clinicians should know about safely discontinuing PrEP, dosages for starting or restarting the medication, and the risk behaviors that require patients to reinitiate treatment.
Q: When is it safe for a patient to discontinue PrEP?
A: The simple answer is you can stop taking PrEP when you are no longer at risk for HIV infection. Intuitively, but honestly, understanding when it is safe to stop PrEP is far from simple. A few examples I give to my patients would be if they fit into the following categories: if they are in a monogamous serodiscordant relationship and their HIV-infected partner is virally suppressed; if they are in a monogamous seroconcordant relationship; if they are able to consistently and correctly use condoms; or if they are abstaining from all sexual activity. Some guidelines advocate that if the person on PrEP has been using daily PrEP, they continue taking PrEP for 28 days after their last exposure before stopping this is extrapolated from the postexposure prophylaxis guidelines, and the need for a month of PrEP after last HIV exposure is an area that requires further research. Other guidelines (CDC, International AIDS Society, the British HIV Association, etc.) recommend taking PrEP for 7 to 10 days after the last exposure. For men who have sex with men who are using “event-driven” or the “2+1+1” PrEP dosing strategy, most guidelines advocate continued use of PrEP for 2 days after their last sexual encounter. I think one of the major challenges to safely stopping PrEP is being able to predict how long a period of reduced HIV risk might continue HIV risk is dynamic. A key aspect to safely stopping PrEP is having a plan for how and when a patient needs to consider restarting PrEP.
Q: What is the difference between risk perception and risk behavior?
A: Risk perception is how a person perceives their own personal risk, whereas risk behaviors are the actual actions (eg, sex without barrier protection, multiple sexual partners of unknown HIV status, etc.). Numerous studies have demonstrated that our perception of risk often does not align with our actual risk behaviors. So, in the context of HIV, a person may perceive themselves to be at low or no risk of acquiring HIV, whereas their actions are, in fact, those that are commonly associated with increased HIV acquisition risk. The reasons for this misalignment are multifactorial but have important implications for PrEP uptake and PrEP persistence.
Q: What do clinicians need to know about PrEP dosing for a patient who is discontinuing the medication?
A: I think this is a moving target, and guidelines are evolving in terms of how long a person should continue to take PrEP after their last potential HIV exposure. At this point, when starting or stopping PrEP, one of the key things to know is what kind of sex your patient is having. Most guidelines agree that for patients who are taking PrEP for whom their HIV acquisition risk is via receptive anal sex and they are employing an event-driven PrEP strategy, patients should continue taking PrEP for 2 days after their last exposure. If the risk of acquisition is via vaginal sex, guidelines vary between 7 days and 28 days after the last potential HIV exposure.
Q: When should a patient restart PrEP? Is the dosing different for someone initiating PrEP for the first time and someone restarting PrEP?
A: At this point, the indications for restarting PrEP are identical to those for someone who is initiating PrEP for the first time. Generally, this includes HIV-negative persons who are at substantial risk of acquiring infection. The specifics are going to vary by region and subpopulation HIV prevalence but typically include men who have sex with men, transgender women, people with HIV-infected partners who are not virally suppressed and other groups at increased risk that may include persons with recent sexually transmitted infections, sex workers or persons who inject drugs. The next part of answering the “when to (re)start PrEP” question is how long before a potential HIV exposure should PrEP be started in order to confer protection. Much like how long to continue PrEP after the last HIV exposure, the lead time for achieving protective PrEP levels is an area of ongoing research. For the most part, the evidence and corresponding guideline) agree that it takes longer to accumulate protective levels in cervicovaginal tissues than in rectal tissues. The so-called “event driven” (or “on-demand” or “2+1+1”) PrEP use strategy is likely an effective option for men who have sex with men, in which starting PrEP involves taking two pills before high-risk anal intercourse, and then one pill a day for the 2 days following this potential exposure. For heterosexual women for whom their risk of HIV acquisition is through vaginal sex, some guidelines suggest that a 7-day lead-in time of daily oral PrEP would be protective, whereas others suggest needing as many as 20 days of daily oral PrEP to accumulate sufficient protective drug levels. I think the data are leaning more toward a shorter (ie, 7-day) period. There is no difference in PrEP dosing between someone initiating PrEP for the first time and someone restarting PrEP.
Just as HIV risk changes over time, so, too, can we anticipate that PrEP use will change start, stop and restart. Patients, providers, and policymakers will need to develop strategies to help keep people on PrEP (with good adherence) when they need it, and safely navigate PrEP discontinuation when the drugs are no longer needed.