Is On-Demand 2:1:1 PrEP Safe?
* In this article, we will be discussing the emerging topic of On-Demand PrEP.
On-Demand or 2:1:1 PrEP is a newly introduced therapeutic regimen for HIV prophylaxis. Traditional regimens for PrEP include a daily administration of the medication. Usually, PrEP is administered for 7-28 days before condomless sex ( 7 for anal, 21 for vaginal).
SO, Is On-Demand 2:1:1 PrEP safe?
The Short Answer is Yes, But. On-demand PrEP is a newly introduced regimen for HIV prophylactic therapy. On-demand PrEP was tested successfully as prophylactic therapy for men that have anal sex with men. However, it wasn’t tested on other groups including vaginal or front hole sex.
Prevenir (1)Study Results
|
Treatment |
Follow Up Patient (years) |
HIV incidence per 100 Pts Years (95% CI) |
|
TDF/FTC (Daily) |
443 |
0 (0-0.8) |
|
TDF/FTC (On-Demand) |
506 |
0 (0-0.7) |
What is On-Demand or 2:1:1 PrEP regimen?
On-Demand PrEP is a new recommended PrEP regimen for males that have infrequent anal sex with males.
It is administered in 2 doses before sex and 2 doses after sex (in case the sexual activity was not continued on the days that follow). 2 pills (double dose) should be taken 2-24 hours before the intercourse, afterward another pill should be taken 24 hours after the first pill (which was taken before the intercourse) and the last pill 48 hours after the first pill (which was taken before the intercourse).
Can I take On-Demand PrEP if I continue to have sex after?
Yes, you can. Although On-Demand PrEP is recommended for infrequent unprotected sex, it can be used if you have more than one-time intercourse.
So let’s clarify it:
Let’s say you planned sex for today and you took 2 tablets before sex, however, things went well and you want to have sex again tomorrow. In this case, you will continue to take a tablet a day, at the same time you took your first tablet, as long as you have sex.
When you finish with sex and you want to stop with PrEP, then you should take 2 last tablets in the 2 days that follow your last sexual activity.
Is on Demand 2:1:1 PrEP safe for any anal sex?
The answer is not clear yet. Although the Prevenir research included small numbers of heterosexual and transgender participants, that had only anal sex (not vaginal or front hole sex), the numbers are not large enough to reach clear statistical significance. The clear cut results we have are about MSM anal sex. Therefore, many experts think that heterosexual anal sex and other forms of anal sex need to follow the daily protocol. (For more information about PrEP typical regimen visit our Step 3 page on PrEP’s administration).
Which Studies Prove that on Demand 2:1:1 PrEP protocol is safe?
There are 2 main studies that support on Demand PrEP. The first Is the IPERGAY(2) study. In this study, they researched gay and bisexual men at high risk for HIV infection. The control group received a placebo while the treatment group received the on-Demand PrEP protocol with TDF/FTC.
14 infections have been detected in the control group and only 2 infections in the treatment group. Later it was proved that those 2 patients have stopped the therapy months before the infection.
The second study was the European study of Prevenir. In this study, 1435 MSM have been divided into 2 treatment groups. One group was on the traditional PrEP daily treatment while the second group was taking On-Demand PrEP therapy. both groups had zero HIV infections.
Obviously, both studies show that On-Demand PrEP is highly effective in MSM.
What Do the critics of On-Demand 2:1:1 PrEP regimen say?
Many doctors raise the claim that in the On-Demand regimen, patients won’t be able to reach the optimal blood concentrations of the medication before sexual intercourse. Optimal concentrations are usually achieved in the anal tissue after 7 days from PrEP initiation, when on the daily regimen.
Furthermore, according to previous research, we know that the daily protocol success rate is 99% and it doesn’t drop dramatically if you forget a couple of doses a week. For example, taking PrEP 4 times a week gives you 94% of protection. However, if you forget one more dose, the risk increases by 20 percent. This means that any forgetting in the On-Demand protocol is not possible and can cause infection in high percent.
Some of the critics of the IPERGAY study claimed that the fact that many of the patients had frequent sex rather than infrequent. This way the patient has been actually on a nearly daily regimen due to the frequent use of PrEP, therefore we cannot draw a conclusion from this study on the regimen.
Is on Demand 2:1:1 PrEP approved by the FDA?
No, only a daily PrEP regimen is approved by the FDA. However, the International AIDS Society-USA endorses PrEP 2-1-1 as do clinical guidelines in France, the UK, Canada, and Australia.
What are the positive aspects of the On-Demand 2:1:1 PrEP regimen?
Higher compliance
For people that have infrequent unsafe sex activity (condomless), taking daily PrEP can be difficult. Moreover, in this case, there is a higher possibility for lower compliance, with the daily regimen, as people tend not to comply in case they take a. medication only for scarce circumstances.
Lower expenses
Another positive aspect is the price. On-Demand sex can be only 4 tablets a month (depending on the number of sexual encounters), while a daily PrEP regimen is always 30 tablets a month. In many countries, this difference can cost hundreds of dollars.
necessity
On-Demand PrEP is necessity in some cases. There are many circumstances in which people are “caught in the moment” and they might have condomless sex, while not being on PrEP therapy the days before. In those cases, On-Demand PrEP can be useful.
What are the side effects of On-Demand PrEP?
On-Demand PrEP’s side effects are similar to daily PrEP’s side effects. Among these side effects, nausea and other gastrointestinal symptoms are the most common. To learn more about PrEP’s side effects check our PrEP guide.
What are the medications that are approved for On-Demand PrEP?
Research showed that Truvada or its generic form TDF-FTC is safe for On-Demand PrEP protocol. On the other hand, other forms of PrEP like Descovy (Emtricitabine / Tenofovir alafenamide) have not been researched yet.
I’m a transgender on hormone therapy, is On-Demand PrEP safe for me?
In the iFACT(3) study, research showed that there are drug interactions between hormonal therapy regimens and PrEP. These interactions caused lower blood values of PrEP. The clinical significance of this decrease in concentration is not clear. However, further research is needed on this topic to further understand the regimen and its safety. As we have no reassuring research for the safety of On-Demand PrEP for transgenders on hormone therapy, we strongly recommend you to follow the daily PrEP regimen and consult your doctor regarding any questions you have. Moreover, you can follow us, as we will be updating regarding any new research on the topic.
So what is “Infrequent sex” for the On-Demand PrEP regimen?
On-Demand PrEP is recommended for infrequent condomless sex, however, infrequent might sound vague for many people as it can be subjective.
Many experts agree that On-Demand PrEP should be used if you have up to 3 sexual encounters a month (4).
Why can’t I use the On-Demand PrEP regimen for frequent sex?
On-Demand PrEP regimen achieves lower blood drug concentrations than the traditional daily regimen. It takes around 7 days of consecutive PrEP daily uptake, to reach optimal drug concentrations in the anal tissue. Therefore, the protection in the On-Demand regimen is not optimal, concentration wise. However, we don’t know the clinical significance of this. The more unsafe sexual encounters, the higher the probability to be infected, as encounters with high viral load carriers or aggressive sex (anal tissue tear) are more probable to happen. Thus, in these cases we want you to have the highest levels possible of PrEP in the blood.
Another reason is that, if you have more than 3 sexual encounters a month, and take On-Demand PrEP this means you will be taking PrEP for more than half of the month. This increases your probability to forget to take the medication as it can be confusing. Thus switching to the daily regimen is the recommended solution.
What is the Follow Up Plan for On-Demand PrEP?
The follow-up plan for On-Demand PrEP in most countries is similar to the follow-up needed for daily PrEP regimen. This plan includes once in 3 months clinic visits to asses your health status, perform blood tests including 4th generation Elisa HIV test, blood creatinine level test, and STI assessment.
For more about the PrEP follow Up program, check our PrEP guide.
Conclusion
As research shows many PrEP candidates have difficulties to follow the daily PrEP regimen, many ongoing pieces of research are examining alternative regimens.
The IPERGAY and Prevenir studies showed daily On-Demand PrEP (TDF/FTC) to be safe for anal sex mainly for males that have sex with males. Moreover, TDF/FTC provides an alternative for patients with kidney issues as well as low-income people as lower amounts of the drug need to be consumed.
Further research is needed in order to establish evidence for the safety of this protocol for heterosexual/transgender anal sex as well as vaginal sex. Other forms of PrEP like Descovy (Emtricitabine / Tenofovir alafenamide) need to be examined for this protocol.
Resources
1. http://programme.aids2018.org/Abstract/Abstract/13278
2. https://www.nejm.org/doi/full/10.1056/nejmoa1506273
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625338/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625338/