I’m a guy who has sex with other guys. I stopped using PrEP during the initial lockdown phase of the COVID-19 pandemic in my town, but I really miss sex and want to feel touched again. I found a guy who has tested negative for COVID (I’m negative as well) and really wants to top. How long do I have to take Truvada for PrEP before I’m protected again?
The COVID-19 pandemic has been challenging for so many, both physically and emotionally. For many gay men, the lockdown has meant going long stretches of time without contact or connection, so it makes sense that you want to find a rational and medically sound way to give and receive touch and sexual intimacy.
Thankfully, the World Health Organization (WHO) offers empirically driven guidelines for how to stop and restart HIV pre-exposure prophylaxis (PrEP) for anal sex: They recommend the use of “event-driven” PrEP, or ED-PrEP for short.
In their words, “Given the clinical evidence for the efficacy of ED-PrEP among men who have sex with men ... it is suggested that men who have sex with men starting PrEP begin with a single loading dose of two tablets of FTC/TDF ... taken two to 24 hours before sex, whether the intention is to use daily PrEP or ED-PrEP.” (FTC/TDF is medical shorthand for Truvada, which is made up of two drugs, emtricitabine [FTC] and tenofovir disoproxil fumarate [TDF].)
What does this mean? The science has consistently shown that these three steps provide the maximal protection for anal sex:
- Take two doses of Truvada at the same time two to 24 hours before having sex.
- Take one dose about 24 hours later.
- Then take another dose 24 hours after that.
This approach is also called “on-demand” or “2-1-1” dosing. The WHO also recommends this as a start-up regimen for those intending to eventually use PrEP on a daily basis.
During U.S. Food and Drug Administration hearings in August 2019, evidence was presented showing that three single doses of Truvada provided more than 90% of protection for anal sex. Earlier research has shown that even one dose of Truvada prior to anal sex appears to confer about 77% protection for anal sex. No matter which way you look at it, using Truvada for PrEP rapidly provides substantive protection for anal sex.
U.S. Federal Guidelines Have Made PrEP Dosing More Confusing
There remains much confusion on the subject of PrEP dosing, in part due to reluctance within the Centers for Disease Control and Prevention (CDC) to rely on current scientific data to inform their PrEP guidelines.
Originally written in 2014 and most recently updated in 2017, the CDC guidelines state, “The time from initiation of daily oral doses of TDF/FTC to maximal protection against HIV infection is unknown.” They go on to say that, according to “preliminary data” on how tenofovir enters the bloodstream, the drug reaches its maximum concentrations “in blood after approximately 20 days of daily oral dosing, in rectal tissue at approximately seven days.”
But when we discuss PrEP’s efficacy, tenofovir is not the only contributor: TDF alone does not provide reliable protection from HIV and does not provide an accurate model for how PrEP protects. Truvada and Descovy (emtricitabine/tenofovir alafenamide, a newer PrEP formulation) both contain a significant amount of a second HIV drug, FTC.
What “preliminary data” is the CDC referring to? In the agency’s 2017 guidelines, it relied on the following two citations to support the suggestion that it takes about seven days to reach maximum intracellular concentrations in rectal tissue:
Citation #1, published in 2010, argues that PrEP absorption in rectal tissues needs to be studied separately from blood markers, given that "tenofovir-DP accumulates in tissues relevant for HIV prevention and that concentrations according to cell/tissue type may be different relative to the reference PBMC compartment." Back in 2010, there was no science that explained how quickly PrEP reaches rectal tissues.
Citation #2 is a slide presentation given in April 2012 at the 13th International Workshop on Clinical Pharmacology of HIV Therapy. During the presentation, Peter Anderson, Pharm.D., shared data demonstrating that PrEP reaches an effective concentration of about 90% after three single doses.
In other words, the CDC has apparently been unable to verify its own suggestion that PrEP takes seven days to reach maximal protection in rectal tissues, even while its citations support the recommendation of three doses for 90% effective protection. While 90% may not be the maximal level of protection that PrEP can achieve, it’s sure a lot higher than zero, and three doses is a lot less than seven. Furthermore, subsequent studies have validated that using the on-demand strategy effectively offers 99% or more protection.
Oddly, even the CDC itself acknowledges that on-demand PrEP is suggested by some health departments in the U.S. (New York City’s, for example)—even as it stands by its outdated guidelines.
Why is the CDC continuing to provide medical guidelines that do not accurately reflect current science? Attempts to get an answer to this question for this article were unsatisfactorily resolved. CDC spokesperson Jacqueline Petty repeated the guidelines’ statement that Truvada “reaches maximum intracellular concentration associated with protection from HIV for receptive anal sex at about seven days of daily use," but provided no new evidence or data to support this claim.
“Right now, it is especially important that our medical institutions gain our trust by sticking to the science,” said Michael Chancley, a PrEP navigator in Atlanta and the leader of the international PrEP Facts Facebook group. “We’re getting conflicting messages about everything from COVID vaccines and transmission to PrEP efficacy and side effects.”
When medical agencies like the CDC fail to include accurate scientific data in their PrEP guidelines, it can create confusion and uncertainty—and it can impede PrEP uptake in communities that stand to benefit most. “As PrEP navigators, we cite the CDC when discussing PrEP because the CDC is a trusted source,” adds Chancley. “But when the information is in conflict with clear science, it hinders our relationships with patients.”
The Bottom Line on Restarting PrEP
All of this is to say, dear reader, that when it comes to restarting PrEP after stopping, you have many proven options. When in doubt, I encourage people to use evidence and science to inform their sexual health decisions. The WHO makes the science behind restarting doses for anal sex very clear in its 2019 PrEP guidelines, and the science supports the efficacy of 2-1-1 dosing for anal sex.
Included in those WHO guidelines as well are additional best-practice recommendations:
- Get a confirmed HIV-negative test result before restarting PrEP, when possible.
- Test for HIV again every three months.
- Get regular testing for sexually transmitted infections every three months (or even more frequently, if you can).
- While you’re on PrEP, get routine labs and creatinine testing every six months (or more, as directed).
I hope you are able to move forward during these difficult times with joy, connection, health, and science.