Four PrEP Pills on Demand Can Stop HIV

Heather Boerner

November 08, 2019

PORTLAND, Oregon — San Franciscans have a new option when it comes to HIV pre-exposure prophylaxis: PrEP on-demand.

They can still choose daily PrEP with the combination of emtricitabine plus tenofovir desoproxil fumarate (Truvada, Gilead Sciences) or emtricitabine plus tenofovir alafenamide (Descovy, Gilead Sciences). But now, they can choose on-demand PrEP — dubbed "PrEP 2-1-1 for anal sex" by the San Francisco AIDS Foundation — to prevent HIV, which consists of two pills of Truvada at least 2 hours before sex and one pill on each of the two following days.

"It's a great option for people who are having a little less frequent sex and are able to plan ahead," said Janessa Broussard, RN, AGNP-C, director of clinical services at the AIDS foundation.

And for providers who are new to prescribing PrEP — whether daily or on the 2-1-1 protocol — "it's a perfect time to come on board because we have a ton of evidence to support both" approaches, she told Medscape Medical News.

From March to August, 517 primarily gay men opted for the new approach at San Francisco AIDS Foundation clinics. None have acquired HIV, Broussard reported to a standing-room-only crowd here at the Association of Nurses in AIDS Care 2019 conference.

Daily, 2-1-1 , or Both

Nearly 2 years ago, patients started to show up at the Magnet clinic in the Castro District with a question: Could they have access to the protocol in which Truvada is used not daily, but around the time of sex? Research in Europe was showing that it prevented HIV transmission in gay men.

"Some clients disclosed that they had switched themselves to on-demand PrEP," Broussard explained. So the foundation figured it should develop a plan to address the issue.

They added a third — and equal — option for HIV prevention in the form of the 2-1-1 protocol laid out in the large clinical IPERGAY trial, as reported by Medscape Medical News.

In that study, 400 gay men with multiple risk factors for HIV were randomized to the on-demand protocol — a double dose of Truvada 2 to 24 hours before sex, one pill 24 hours after the first set of pills, and the another pill 24 hours after that, assuming they didn't have sex again — or to placebo.

HIV acquisition was 86% lower in the 2-1-1 group than in the placebo group.

Research shows that 2 to 24 hours is enough time to bring concentrations of the drug in rectal tissue up to protective levels, Broussard reported.

In an open-label extension of IPERGAY, acquisitions dropped 97%. "So it worked better in real life," she pointed out.

In a follow-up study, PREVENIR, which compared daily with on-demand PrEP in 1435 people — gay men and some transgender women — no participants in either group acquired HIV.

And daily PrEP is up to 99% effective, according to a report from the Centers for Disease Control and Prevention (CDC).

Those findings, along with real-life data from men using the approach in Europe and Canada — zero HIV acquisitions with 2-1-1 to date — and the endorsement of the San Francisco Department of Public Health, convinced the AIDS Foundation they were ready to offer the protocol. The evidence is solid, Broussard said

Considering the Right Approach

Although other clinics offer 2-1-1 as a last resort for people who are not compliant with daily Truvada, "we decided to offer it as an equal option," she said.

However, the protocol is not available to people having vaginal sex, because none of the studies have been conducted in women, and evidence suggests that Truvada doesn't concentrate as quickly in vaginal tissue as it does in rectal tissue. And it is not indicated for people with unresolved hepatitis B because the drugs in Truvada can reactivate the virus.

Magnet doesn’t recommend the 2-1-1 protocol with Descovy because there have been no trials of on-demand PrEP with that combination, Broussard explained. The US Food and Drug Administration has not approved on-demand dosing of either Truvada or Descovy, and the drug companies haven't asked.

"But we have always" prescribed off-label in HIV, she pointed out. "We've always been rogue. Doctors who prescribe 2-1-1 will be in good company."

Because early studies have shown that feminizing hormones can decrease the level of Truvada in the blood, Magnet suggests daily PrEP to transgender people using hormones. However, when transgender patients present to the clinic, clinicians give them all the facts, including that it is not clear whether that decrease in tenofovir is associated with increased acquisition of HIV, and let them choose, said Broussard.

Clinics also offer a "PrEP both" option. People can vary their PrEP dosing to match their sexual activity. When they are having more sex, they use Truvada daily; when they are having less sex, they use the 2-1-1 protocol.

"We wanted to help individuals create what works best for them," she said. But either way, "you have to be able to plan ahead for this approach. You can't spontaneously use this prevention method."

That's why she generally doesn't recommend PrEP 2-1-1 for adolescents. "That waiting 2 hours can be problematic," she said, eliciting laughs from the audience.

You have to be able to plan ahead for this approach. You can't spontaneously use this prevention method.

Five months after PrEP 2-1-1 became an option at foundation clinics, most people were still on the protocol they chose at their initial visit. People who had a partner with HIV or a high number of sexual contacts were more likely to have chosen daily dosing.

But 207 people opted for 2-1-1 and 76 for both. By August, 164 people had switched from daily to 2-1-1 dosing and 146 people new to PrEP opted for the 2-1-1 protocol, so 517 people were using 2-1-1 PrEP, Broussard reported.

The cutoff for PrEP 2-1-1 is three sexual contacts a month. Any more than that and it becomes easier to take a daily pill than to keep track of 2-1-1 dosing, she said.

That’s because you have to have at least one 24-hour period in which you don't have sex and are still fully covered by the drug. So if you take your double dose at 8 PM and have sex that night, you take the next dose at 8 PM the next day and then the following day. But if you have sex again during that period, you have to take at least one more Truvada pill at 8 PM. At that point, you're just taking it daily, she explained.

"We also advise people that taking a loading dose closer to 24 hours before sex is better than 2 hours," she said. "You are more protected at 24 hours than at 2 hours." But, she added, a 2-hour head start provides enough drug in the tissue to prevent transmission.

If patients do miss a dose during the 2-1-1 process, Broussard and her colleagues advise patients: "Take two Truvada and call us in the morning."

At that point, they add dolutegravir for 30 days as postexposure prophylaxis. Since March, they've prescribed dolutegravir to 18 people, Broussard reported.

"With the number of people we see, that's a relatively low number," she said. "When I've done chart reviews, many of these are folks we didn't advise to go on 2-1-1 but they decided to anyway. Usually we use this as an opportunity to help them decide they need to do PrEP daily."

Take two Truvada and call us in the morning.

An understanding of how quickly Truvada builds up in rectal tissue has changed the way some providers prescribe all dosing schedules of PrEP.

Instead of telling people who are starting daily PrEP to take the drug for 7 days to be sure they're covered, Broussard and her colleagues now advise new PrEP patients having anal sex to take two pills their first day so they will be protected within 24 hours, whether they're doing 2-1-1 or not.

In San Francisco, they use a jump-start to HIV prevention, with a kit to match: four pills in a small bottle with an alarm cap.

Clinicians take these jump-start kits with them to do HIV testing and PrEP counseling at events. After intake to determine eligibility and discuss the different PrEP approaches, patients who choose PrEP get the kit. Providers encourage patients to take their loading dose immediately so they can be ready to go in 2 hours.

"This," she said pointing to a photo of the compact kit, "can stop HIV."

A Game-Changer

The loading dose could change practice, said Kim Hutchinson, RN, from the Old Town Clinic, a federally qualified health center for low-income people in Portland, Oregon.

Providers at her clinic offer PrEP, she explained, but "it's not as widely adopted as it should be." And for their clients, who are largely people with unstable housing and addiction and mental health challenges, the CDC recommendation to wait a full 7 days after the initiation of PrEP for sex "just isn't realistic," she said.

"A lot of our clients are using sex to get their needs met," she said. "This is a much more useful strategy."

She's now inspired to start a nurse-run PrEP clinic for her patients, she said.

It's already changed practice for Jeffrey Schaffer, RN, from Outer Cape Health Services in Provincetown, Massachusetts.

When he heard about PrEP 2-1-1 from Broussard's predecessor, he was inspired. Provincetown is a popular destination for gay, lesbian, bisexual, and transgender community members during the summer. So when he heard about Magnet's work, he visited the clinic and learned about the protocols, which are available on the San Francisco AIDS Foundation website. He then asked the Provincetown Department of Health to institute PrEP 2-1-1.

After some apprehension, "they became interested in discussing it. Just like anything, when you say, 'I want to run this,' people will say, 'We can't do that.' But of course we can."

Association of Nurses in AIDS Care 2019. Presented November  7, 2019.

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