For people having anal sex, PrEP 211 is as effective as daily PrEP
Daily use of PrEP reduces the risk of HIV infection by up to 99%. Yet there are a few factors that may keep people from seeing daily PrEP as an option: the high cost of Truvada, an aversion to long-term or daily medication use, or infrequent sex.
“On-demand” PrEP—also known as PrEP 211—is an alternative method of dosing that may speak to these concerns, making PrEP an option for more people than ever before. PrEP 211 is named for its schedule of dosing: 2 pills are taken 2-24 hours before sex, 1 pill 24 hours after the initial dose, and one final dose 24 hours later (find more info about this strategy). Clinicians only recommend PrEP 211 for people having anal sex, since the drug may not be present in levels high enough with PrEP 211 dosing to protect vaginal tissues.
“We want folks to know about PrEP 211 because this dosing strategy has been evaluated substantially in Europe and elsewhere, and available data show 211 works well when done correctly,” said Chris Hall, MD, vice president of medical affairs at San Francisco AIDS Foundation. “211 is likely to be a better fit for many people having less frequent sex, compared to taking medication once day.”
Here’s what we know about how well PrEP 211 works to prevent HIV infection.
Comparison between daily PrEP and 211 dosing
Being conducted in the Paris region of France, the Prevenir study is providing solid answers about exactly how effective PrEP 211* is. The study, which is ongoing until 2020, has enrolled mostly men who have sex with men (and a few trans people and heterosexual people) to compare daily PrEP with PrEP taken around the times of sex.
Participants are able to choose which regimen they take, and are able to switch back and forth during the study. The researchers are measuring HIV infections, PrEP adherence, if each sexual encounter is “covered” by PrEP, and sexual behavior.
Study results presented at the AIDS 2018 conference included data from 1,629 participants, with 443 patient-years of daily PrEP use and 506 patient-years of PrEP 211 use. The average amount of follow-up time in this analysis was seven months.
Adherence to both strategies was high. “Correct use” at last sexual intercourse was reported by 95.8% of people taking PrEP daily and 96.2% of people taking PrEP 211.
There were zero HIV infections among people taking daily PrEP, and zero HIV infections among people taking PrEP 211. The HIV incidence rates for daily and 211 dosing were both 0 per 100 patient-years. The researchers estimated that 85 HIV infections were averted during the course of this portion of the study.
Because people were able to choose which dosing strategy they wanted to use, the researchers found differences in who was using each strategy. As might be expected, people taking PrEP daily were having more frequent sex than people who opted for PrEP 211 (people taking PrEP daily also tended to have more partners).
Summary: In a study with more than 1,500 people followed for about 7 months, PrEP 211 was as effective as daily PrEP with neither strategy resulting in any HIV infections.
*In the Prevenir study, the researchers described the dosing strategy as PrEP “on-demand” instead of as PrEP 211. The dosing strategies are the same.
The first PrEP 211 study: PrEP 211 compared to placebo
The most well-known and first PrEP 211/on-demand study, named IPERGAY, was conducted in France and Canada with men who have sex with men and transgender women between 2012 and 2016. The randomized controlled portion of the study included 414 participants and the open-label follow-up included 361 participants.
An early analysis of the unblinded study data during the randomized controlled portion of the study found that the 211 regimen significantly reduced HIV risk compared to placebo, so the study was quickly changed to allow everyone access to PrEP 211. Final study results presented in 2015 showed that PrEP 211 reduced risk of HIV infection by 86% compared to placebo.
Two people acquired HIV taking PrEP 211 during this portion of the study (compared to 16 people in the placebo group). However, the researchers did not detect the PrEP medication in plasma samples taken from these individuals, which led the researchers to believe the two people were not taking PrEP around the time of their infections.
The continuation of the study (called the “open label” phase) provided a real-world look at how people might use PrEP 211. Participants were followed for an average of 18.4 months, and the study collected a total of 518 person-years of data.
One HIV infection happened during the open label phase of the study, in a person who likely had not taken PrEP for many months when he was diagnosed.
Overall, this part of the study found that PrEP 211 reduced risk of HIV infection by 97%.
One lingering question after IPERGAY study results were released involved the effectiveness of PrEP 211 for people having sex less frequently (and therefore taking PrEP less frequently). Many people in IPERGAY reported frequent sex—at least one sexual encounter per week—which resulted in taking 4 pills per week or about 16 pills per month. Does PrEP 211 work even if you aren’t taking that many pills on average per month?
To share the answer this question, lead IPERGAY researcher Jean-Michel Molina presented the results of an IPERGAY sub-study in 2017. The sub-study included people in IPERGAY who used less than the median number of pills per month by people in the entire study. These people had an average of five sexual encounters per month and took an average of 9.5 pills per month.
Even among these people taking PrEP less frequently, there were zero HIV infections (compared to six infections among people included in a comparison placebo group)—leading the researchers to estimate a relative risk reduction of 100% for people who used PrEP 211.
Summary: In the first PrEP 211 study conducted in France and Canada, PrEP 211 was shown to effectively reduce risk of HIV infection among a few hundred men who have sex with men and a very small number of trans women.
Large clinical trials have shown that PrEP 211 is an effective way to prevent HIV infection. When used correctly, PrEP 211 is as effective as daily PrEP for people having anal sex.
Most studies of PrEP 211 have mostly included men who have sex with men, and very small numbers of transgender women. It is less certain how well PrEP 211 works for people having vaginal sex.
The International AIDS Society-USA endorses PrEP 211 as do clinical guidelines in France, the UK, Canada and Australia. The FDA in the U.S. has not reviewed, and has therefore not approved PrEP 211.
Molina, J.M. and colleagues. Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study. Lancet, 2017.
Molina, J.M. and colleagues. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. NEJM, 2015.
Molina, J.M. and colleagues. Incidence of HIV-infection in the ANRS Prevenir study in Paris region with daily or on-demand PrEP with TDF/FTC. AIDS 2018.