Switch On Your HIV Smarts.

From Research to Real World: A PrEP Q&A with Dr. Robert Grant

, by Reilly O'Neal

Robert Grant (photo: Gregory Fowler)

Robert Grant (photo: Gregory Fowler)

PrEP, short for pre-exposure prophylaxis, is a comparatively new HIV prevention tool that won FDA approval in 2012 based on several studies, including the iPrEx trial of PrEP in gay and bisexual men and a smaller sample of transgender women who have sex with men. In iPrEx, daily PrEP was associated with an estimated 99% reduction in HIV incidence.

CDC guidelines today advise that providers recommend PrEP to anyone at increased risk for HIV—but the work is far from over. PrEP demonstration projects are picking up where clinical trials left off, addressing questions to help us understand how people use PrEP, how well it works, and how we can maximize PrEP’s benefits in the “real world” outside controlled-trial settings.

Data from one such demonstration project, the iPrEx Open Label Extension (OLE), made waves in a late breaker session at the AIDS 2014 conference in July. “Adherence has to be good, but it does not have to be perfect,” reported iPrEx protocol co-chair Robert Grant, MD, MPH, of the Gladstone Institutes, the University of California at San Francisco, and San Francisco AIDS Foundation.

As previously reported, taking four or more pills per week was linked with 100% protection; no participants who took PrEP at least four times weekly acquired HIV during the OLE study. Overall, HIV incidence dropped 50% in the PrEP arm, which included participants who opted to receive PrEP but took it inconsistently or stopped using it altogether.

What do the iPrEx OLE findings indicate for PrEP implementation—and how can we put the data to good use? In this in-depth Q&A, Dr. Grant addresses these questions, debunks a major PrEP myth, and talks about the transformative power of PrEP-protected sex.

What do these results from iPrEx OLE mean for PrEP use in the real world?

The good news for implementation is that the majority of people wanted to try PrEP—76% overall—when it was provided free of charge by an experienced provider. When we eliminate restrictions to the supply of PrEP, people do want it.

Another important finding was that people who need PrEP the most want it the most. We saw this at three different levels: Among people who reported higher-risk behavior, retention in the follow-up study was higher, uptake of PrEP was higher, and adherence was higher. We saw that the people who could benefit the most from PrEP used it the most, and that’s good news.

The other good news is that adherence has to be good, but it does not have to be perfect. Men who have sex with men can miss two or three doses a week and still have a very high level of protection.

The challenge, we found, was ongoing engagement—which is different from adherence. Adherence is typically a measure of the proportion of prescribed tablets an individual actually takes. What we’re seeing is different: Some people in OLE experiment with PrEP, and then stop using it. This is much more common in younger populations: 18-to-29-year-olds stop taking PrEP more frequently than 30-to-40-year-olds, and 30-to-40-year-olds stop taking it more frequently than people over 40. So we think this has to do with being young and wanting to experiment with PrEP.

These data seem to highlight one of the strengths of PrEP: People can take it if and when it makes sense for them, and stop when it doesn’t.

Taking antiretrovirals for PrEP is different from taking them for HIV treatment, in significant ways. Treatment for HIV is something people need to start early and stick with long term. PrEP is different. People go through “seasons of risk,” periods of their lives when they are at risk for acquiring HIV, and PrEP is appropriate for those times. In periods when they have negotiated safety with a partner or they’re just not having much sex, they may find they don’t need PrEP. It’s actually appropriate that some people stop PrEP, because they’re in a different phase of their life and they no longer need it.

For sure, some of the people who stopped PrEP in our study did still need it, and some acquired HIV after stopping PrEP. This not an adherence problem; it’s that some people—primarily younger people—stop using it altogether because they feel they don’t need it. I think that tells us we need to find more effective ways of engaging younger people in HIV prevention.

At AIDS 2014, one of your iPrEx OLE colleagues, Kim Koester, presented data on PrEP and “risk compensation”—the idea that people will start taking PrEP, stop using condoms, and begin having “riskier” sex. Risk compensation often comes up as a potential downside of PrEP. What can you tell us about the OLE findings in this area?

We don’t see evidence for risk compensation in our studies, and Kim Koester gave us a good explanation for why not: People on PrEP are being more mindful about sex. The beauty of PrEP, as Kim reported, is that it provides opportunities, in calm moments, to think through sexual plans and harm-reduction strategies that allow people to protect themselves in a variety of ways.

The theory of risk compensation assumes sexual decisions are rational, take long-term consequences into consideration, and are driven mainly by fear. But in the heat of the moment, decisions happen based on other factors, including opportunity, and attraction, and loneliness. At that moment, sexual behavior may have nothing to do with fear of HIV; the heat of the moment is about the moment.

Interestingly, in our studies, PrEP users themselves sometimes say, “Well, if I’m going to use PrEP, I’m going to stop using condoms.” They often surprise themselves when they continue to use condoms. We can see that if people are accustomed to using condoms consistently, they tend to continue to use them after they start PrEP. People get engaged in PrEP services and start thinking about HIV in calm moments, and they begin finding a variety of ways of protecting themselves—and we’re seeing the benefits of that.

What exactly does the “risk” part of “risk compensation” mean in the context of a highly effective HIV prevention tool like PrEP?

We haven’t see risk compensation in our PrEP work, but the point you’re making is an important one: If PrEP really is highly effective, then in fact it is safe for people to have sex, and they don’t have to worry so much about HIV if they are taking PrEP.

The concern is that we may see an increase in syphilis transmission; we already have an epidemic of syphilis in many of our cities. PrEP does not prevent syphilis, gonorrhea, chlamydia, or other sexually transmitted infections, and it also does not prevent pregnancy. So it’s important to understand the limitations of PrEP.

I think the other reason to be concerned is that PrEP is not universally available. It can be hard to find a provider who is willing to prescribe PrEP. If a few men on PrEP are having condomless sex with many partners and reframing sexual norms in a community, then other men in that community who are not on PrEP (either because they don’t know about it or haven’t been able to access it) may be at higher risk if they follow those evolving sexual norms. So it’s essential that we make PrEP available to everyone who could benefit from it, and that we highlight the limitations of PrEP.

But the fact is, we just don’t see risk compensation happening in our studies, and it’s hard to find evidence that people’s sexual decisions are always rational, or that fear is the major determinant of those decisions. Often when we hear people describe their sexual decisions, they don’t talk about fear—they talk about how attractive the guy was, or how fun the situation was, or how lonely they were, or how much they were in love.

Yet for so many years, fear has been a fundamental component of HIV prevention messaging. What are the implications of PrEP for that aspect of sexual culture?

I think we need to understand the limitations of fear-based messaging. For many years, we used fear as a way to foster behavior change. Sadly, I think all we did was make people afraid. There isn’t much evidence that fear-mongering changes behavior that matters.

And the reason is becoming clear. We know from personal experience as well as from the field of behavioral economics that in the heat of the moment—whether it’s a sexual moment, a purchasing moment, or another decision-making moment—decisions are typically not based on long-term considerations. They’re based on short-term considerations: attraction, desire, or how lonely a person is. Trying to change behavior in the heat of the moment is notoriously challenging.

What we can influence is contemplation, decisions, and plans in calm moments. That’s the value of PrEP: It gives people an opportunity to think about HIV and their sexual goals in calm moments.

In the 1980s, when HIV first struck, it was an incredibly frightening and chaotic time. People were dying, and we didn’t know why or what we could do about it. It was extremely traumatic, and as a consequence, we’ve gotten stuck in the ‘80s. We have this notion that if we ever stop being afraid like we were in the ‘80s, then all hell will break loose.

That kind of fear is impossible to sustain; we get tired of it, we become numb to re-experiencing the trauma of the ‘80s over and over, and having to think about HIV during every sexual contact is very stressful.

So I think we have to do something else. And what we can do now is inspire a response to HIV that is developed in calm moments when we can think very clearly about what we want from sex, and how we can get it without getting HIV.

It sounds like PrEP helped relieve some of that stress and fear around sex. People in OLE described feeling more relaxed and less anxious during sex—including those who continued using condoms while taking PrEP.

Yes, we heard people say that—and it was transformative for many people. They realized for the first time that they wanted to be in love, and be loved. That’s one theme we heard: PrEP helps people fall in love, because it creates safety around sex and meaning, and that sometimes leads to love.

Anecdotally, we had people come in and say, “I want PrEP because I want to have sex with dozens of guys, and I want the opportunity to not use condoms.” Then three months later, we see them and they say, “I don’t need PrEP anymore; I’m just having sex with one partner. I don’t want anyone else! I’m in love!” People change.

When you allow people to be safe to have sex, it is transformative. It allows people to contemplate what they really want from sex—and sometimes it’s not what they thought. I think we need to be looking forward to how transformative it can be to create safety around sex.

What else can advocates and providers be doing to help get the most from PrEP?

We also need to be thinking about ways to better engage young people in HIV prevention. iPrEx OLE was a very young cohort of men and transgender women who have sex with men. We found in PrEP cohorts like the Demo Project that high levels of engagement and adherence above 90% are feasible; we did not see that universally in the iPrEx study, and we think that is because the iPrEx cohort is so young, having an average age of 24 when they started PrEP.

So adherence and engagement with PrEP is feasible, but younger people often experiment with ideas—it’s actually a normal social stage, for younger people to explore and experiment, and one of the things they may experiment with is PrEP. The challenge is to help people who really need PrEP to stay on it.

But it’s also important to remember that despite problems with ongoing engagement in iPrEx, we still decreased HIV incidence by 50% in young gay men, many of whom were Latino or African-American. That’s an amazing success. We wish it were higher, naturally, but decreasing HIV incidence by 50% in young gay men is enormous. No other intervention has had such a large impact on HIV rates in young men.

We’re happy with the impact we had. We think it can be greater, but we are happy to finally be doing something that can decrease HIV incidence so dramatically.

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Reilly O’Neal is a freelance writer and former editor of BETA.


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