What’s Next for PrEP? A Q&A with Dr. Susan Buchbinder
San Francisco has been at the forefront of research on PrEP, short for pre-exposure prophylaxis. What PrEP studies are happening in San Francisco right now? And where is PrEP research headed next?
For answers, look no further than Bridge HIV, part of the San Francisco Department of Public Health and a local and global leader in HIV prevention research. Working with Bay Area communities to discover effective prevention strategies in the fight against HIV/AIDS, Bridge HIV was involved with the ground-breaking iPrEx study that first proved PrEP works, as well as the country’s first PrEP demonstration project to see how PrEP can be implemented in “real-world” settings.
We caught up with Susan Buchbinder, MD, director of Bridge HIV, to get the scoop on the latest PrEP research and study opportunities. The research team is working on a number of exciting projects, including looking at new drugs for PrEP and an HIV-blocking lube, and there is even an experimental PrEP shot in the mix.
Since Truvada for PrEP was approved by the FDA in July 2012, why do we need additional PrEP research?
We need as many different strategies as possible because one size won’t fit all. Some people will want to try one approach and others will want to try another approach, so PrEP is not going to be for everyone.
Right now, the only PrEP that has been approved to prevent HIV infection is daily Truvada, which combines emtricitabine and tenofovir. What we know from all the trials is that people who were able to take the pill regularly had higher levels of protection.
There are a number of different questions about how to identify those who would best benefit from PrEP; how to be sure that everyone is educated about PrEP so that people can make an informed decision about whether or not they want to take it; and how best to support an individual who’s decided to take PrEP and help them take it on a daily basis, tracking how well they do and how long they want to stay on it. And there needs to be a lot more training of providers.
That’s a bit of a laundry list, but in simpler terms: How do we support people who decide to use PrEP? How do we educate both individuals and providers about PrEP? How do we deliver it in the most cost-effective and useful way? And how do we use this to our greatest advantage to drive down infection rates?
What studies are happening right now at Bridge HIV to tackle those questions?
There is a collaborative project between San Francisco City Clinic and Bridge HIV called the Demo Project. This is part of a three-city study with sister sites in Miami and Washington, DC, to see among men who have sex with men and transwomen who may have some sexual practices that may put them at risk for HIV.
Do they want to take PrEP? How much do they know about it? And among the people who do want to take PrEP, how do they take it? What do they find are the benefits and downsides of taking PrEP? How long do they stay on it? And what is it like for these clinics to provide it?
The Demo Project is really the first large-scale project in the United States to ask, “How can we deliver PrEP most effectively?”
We are fully enrolled and in the follow-up phase right now. The initial data was presented at CROI in a poster presentation by Dr. Stephanie Cohen. The manuscript will come out in the next several months.
I know Bridge HIV is doing other PrEP studies, too. How are these studies different from other studies that you’ve done?
EPIC (Enhancing PrEP in Community) is addressing the question of what additional support individuals need to help them keep their risk as low as possible and take their PrEP on a daily basis, and get the help they need if they have any side effects or symptoms. Basically, how do you educate and deliver PrEP and help support people in taking a daily pill?
NEXT-PrEP (Novel Exploration of Therapeutics for PrEP) is the HPTN-069 study. HPTN (HIV Prevention Trials Network) is a global network of clinical trial sites, investigators, and community members that are trying to find innovative and ethical ways to prevent new HIV infections in multiple populations. NEXT-PrEP is actually testing a different kind of PrEP agent from tenofovir.
So far, all of the other studies of PrEP have used a tenofovir-based regimen, and there are a number of reasons for that. It’s well tolerated as a once-a-day pill. It’s been shown to protect in animal studies, and there are some characteristics of it that make it a desirable PrEP agent.
But we’re looking for other PrEP agents, as well. NEXT-PrEP is testing a newer drug called maraviroc. It’s a different kind of drug that prevents HIV from locking onto the cell receptors and entering cells and infecting them. Maraviroc is being tested by itself and in combination with some other drugs as well as Truvada.
People are being randomly assigned to one arm or another. They don’t know and we don’t know which arm they’re in, but all of them are getting the best sexual health counseling and prevention strategies that we have. Then we’re seeing how they like and how well they tolerate different medications. You know, what’s easiest to take, and how do people feel, and are there any side effects? So we follow them very closely.
That’s a study that Bridge HIV is doing along with twelve other sites across the country. We’ve fully enrolled our study participants. Some of the other sites still have some more participants to enroll, but it should be fully enrolled soon.
Live outside of San Francisco and interested to see if NEXT-PrEP is enrolling near you? Find out!
Truvada was chosen for iPrEx and other PrEP trials because it’s one of the most safe and tolerable HIV drugs available. How is maraviroc different?
Maraviroc works in a different way. One of the potential advantages of something like maraviroc is the mechanism in which it works. It’s blocking HIV from ever getting inside the cell.
Also, it’s not used as much clinically. One of the concerns that people have raised about PrEP is, “Will people take PrEP and stop, and take it and stop?” PrEP alone is not as powerful as combinations of drugs we use for treatment. If they become infected and start using PrEP again, they may develop resistance to whatever drug they’re using, making that drug no longer an option for treatment.
That’s why it’s really important that people make sure that they’re HIV-negative before they start taking PrEP, and if they stop, they go back to their provider and get tested to make sure that they’re not infected before they re-start taking PrEP.
So there are some potential advantages to maraviroc, both theoretical as well as practical.
What we’re really looking for, though, are some strategies that would make it easier than having to take a pill every day, such as long-acting injectables or something like microbicides, which could be part of a lubricant.
I’m glad you brought up microbicides because I want to switch gears to talk about another important study, MTN-017. Whenever someone talks about that study, they talk about the “rectal revolution.” What is MTN-017? How is the rectal lube used in the study different from what’s being studied for oral PrEP?
What MTN-017 is trying to do, specifically, is address whether people will use locally applied prevention strategies to protect against infection.
One of the theoretical advantages of rectal gel is, if you could deliver the medication to prevent infection to the site where you’re being exposed to HIV, then you wouldn’t have the kind of side effects that you get when you have higher drug levels in your blood. It might be even more protective because you could potentially deliver higher doses.
Tenofovir has been tested as a vaginal gel and been shown to provide some protection in a study of women in Africa. We don’t know whether or not it works rectally. And there have been some studies where tenofovir didn’t protect women against vaginal transmission, and it might be because they weren’t using it on a regular basis.
Another advantage to using a rectal gel for anal sex is that many people, men and women, are already commonly using a lube during anal sex, and this microbicide gel can function as a lube. You don’t have to remember to take a pill or do something extra that you might not otherwise do.
In MTN-017, everybody gets eight weeks of each type of regimen: They get eight weeks of daily oral Truvada; and then they get eight weeks of rectal gel to take every day, once a day; and then eight weeks of the gel to be used just before and after having anal sex.
The total study length is seven months. It’s randomly decided which regimen participants get first, second, and third, but they’ll get eight weeks of one, a week-long break, and then eight weeks of the next one, a week-long break, and then eight weeks of the final regimen.
Here what we’re trying to understand is, what did people like most? How well did they do with a pill versus a gel? What we’re really trying to understand in MTN-017 is how people like these different strategies—because strategies will only work if people use them.
If people like using the rectal gel and it doesn’t cause them side effects or any harm—and earlier studies suggest it doesn’t cause any harm-—then we might next look to see if the gel is be able to provide protection against HIV infection and whether it might be easier to use than taking a pill every day.
Learn more about the rectal lube study—and how you can play a role in it.
Since MTN-017 is looking at safety and acceptability, not how well the gel actually protects against HIV, why would somebody want to join the trial?
People join any of our studies mostly to help their community. It’s really to help try to find an answer to ending new HIV infections globally. We have the most amazing volunteers anywhere.
When people are participating in this study, they are able to give us direct feedback about what they like and what they don’t like about each of these methods. That’s going to help us in developing new products. We’re telling people they shouldn’t expect that they’re going to necessarily benefit from what they’re getting.
They’ll know what they’re getting. It’s not what we call “blinded”: They’ll know when they’re getting the pill; they’ll know when they’re getting the gel. They’ll know if they have to use it once a day or if they have to use it before and after sex. They’ll be able to give us invaluable information about how well people like the different strategies.
Since there’s a lot of community interest around accessing PrEP, what’s the difference between participating in a research study versus getting Truvada for PrEP from your medical provider’s office?
Predominantly the reason why people participate in our research studies is to try to help prevent new HIV infections. For some, like the Demo Project, they have the benefit of getting a year’s worth of Truvada for free.
But with any kind of research study, there are always potential risks involved. They may be minimal risks; when we counsel you about your sexual practices, you might feel anxious. Or when we draw blood, you might get a bruise. But in some trials, risks can be more substantial—and certainly often it requires more of your time to access a drug through a trial.
People who aren’t looking to do something more altruistic and contribute to the science about PrEP, and who know that they’re at risk and want to get something that’s been proven to be effective, should go to their medical providers and ask for PrEP.
We’re still working out the best mechanisms for people to get PrEP from their providers. Some people have medical coverage for getting PrEP. For some others, their insurance policies don’t cover PrEP so it’s more expensive out of pocket. The company that makes Truvada does have assistance programs for people who make less than a certain amount of money to get PrEP at reduced cost or free. There are a number of different options.
Again, we’re trying to find the best way to help providers provide PrEP most effectively to their patients.
Think PrEP might be right for you? Find out how to access it in your community.
Are there any other studies coming down the pipeline for Bridge HIV?
We’re about to get started on a new study that’s not yet enrolling. It’s called HPTN-077. It’s using a long-acting injectable drug to prevent HIV infection.
Rather than taking a pill a day, you get an injection every three months to prevent HIV infection. We think that that’s ultimately going to be easier for people to use. But we don’t know that, so that’s what we ultimately want to understand with this study. We have yet to announce a launch date.
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Megan Canon, MPH, is the social marketing manager for San Francisco AIDS Foundation and the founder of PrEPfacts.org.
If you live outside of San Francisco and are interested in participating in PrEP research studies, check out AVAC’s trial database.