HIV Pre-Exposure Prophylaxis Therapy

Segment Description: Joseph Eron, MD; Paul Sax, MD; W. David Hardy, MD; Eric S. Daar, MD; and Ian Frank, MD, discuss the effectiveness of pre-exposure prophylaxis (PrEP) therapy.

Joseph Eron, MD: So let’s shift a little bit and talk about PrEP, pre-exposure prophylaxis. I think we have a pretty experienced audience, but maybe, Ian, you could take a shot at describing PrEP and how we should be using it—in 2 minutes.

Ian Frank, MD: The use of antiretrovirals [ARTs] to prevent individuals from becoming HIV infected is really 1 of the major advances in our field over the last few years. Studies have shown that if individuals take daily tenofovir and emtricitabine, 1 pill a day on a daily basis, you can prevent nearly 100% of HIV transmissions. It’s that effective.

There are some data with intermittent strategies: 2 pills before sex, 1 a day after, 1 the day after that. A study called the IPERGAY study that was done in France. In the US, the recommendation is still daily tenofovir and emtricitabine, 1 pill a day. It works in men, it works in women, and it works in intravenous drug users, and the CDC has clear guidelines for who should be offered PrEP, and it’s basically individuals who are sexually active in nonmonogamous relationships with partners who are either known to have HIV or whose HIV status is not known.

I think we should be talking about PrEP with anybody who has had a sexually transmitted infection. We should be talking about the use of PrEP in men who have sex with men who are not in monogamous relationships. And it’s really an easy conversation to have. The combination is very safe. There are very few serious toxicities. We should be aware of hepatitis B status in individuals before starting, because tenofovir and emtricitabine is active against hepatitis B, and if you initiate the combination in people with chronic hepatitis B and then ultimately stop, there’s a risk of hepatitis B reactivating and causing acute liver injury.

You want to make sure that somebody doesn’t have acute HIV before starting on PrEP. So if there are symptoms, you may want to do a viral load in addition to a serological assay, because individuals with acute HIV won’t be on totally effective antiretroviral therapy if they get only 2 drugs. And so the risk of resistance is relatively high.

There are a handful of cases of individuals that seemed to have been well adherent to their PrEP combination but still became HIV infected. Sometimes they’ve gotten infected with very resistant virus, and in some cases we don’t really have a good explanation of why they’ve gotten infected. But this is a strategy that is highly effective.

Paul Sax, MD: I guess the big issue, though, is that if the use of it doesn’t overlap with the parts of the country where the risk is the highest.

Joseph Eron, MD: Or the color of the people.

Paul Sax, MD: Exactly. So there’s way more prescribing of PrEP among white individuals than there is among black individuals. A lot of the people we have prescribed PrEP to would fall into the category really of the worry—well, they may be in a monogamous relationship with an HIV-infected partner, but that person is taking [ARTs] already, so their risk is actually really low, if not 0, but they still want to take PrEP just because. I mean, those are not the people at highest risk of getting HIV, and really that’s where PrEP needs to be rolled out.

Eric S. Daar, MD: And that’s the challenge, right?

So it’s estimated based on the people who are candidates for it. There are maybe 1.2 million—that is the number that’s sort of floating around. And only about 10% of those people are on PrEP. And as you say, it’s mostly the people who aren’t in the traditional high-risk group that we really need to be targeting. And in order to do a better job, we need to do better marketing for sure. But I think we also have to, as Ian said, remind everybody that this is simple. We have to stop making this sound as difficult as treating somebody with HIV. It’s simple, easy to take, the screening is very straightforward, and it’s what we need to do. As long as we don’t give it to someone who has HIV, we’re probably going to do mostly good.

Ian Frank, MD: I think 1 of the problems is we’ve medicalized this. If you look at the PrEP guidelines, you’re monitoring patients more often than we’re monitoring people with HIV infections.

W. David Hardy, MD: When you think about it, what thing has made the PrEP rollout difficult is because of that medicalization. In most cases, the only sort of medical interactions many people who are on PrEP have is with their PrEP provider. So why make that more complex, more difficult, more time-consuming for a prevention of the disease. I mean innovative ways of, for example, having people being seen every 3 months—not by a care provider but by a talented pharmacist—to get the test done and then have them interpreted, because those tests are very easy to interpret. You know the way that PrEP is going to work best, especially for individuals at highest risk, is No 1, to market it directly to them and to take it out of medicalization, so people can get it easily and quickly.

Joseph Eron, MD: Yeah, but I still think, and 1 thing that Eric said, you know there might be 100,000 people who have been prescribed PrEP, because that’s the other thing, right, that is sustaining. I mean, you can look at the data, especially in younger people, and maybe it has to do with the medicalization, David, as you just pointed out, but sustaining PrEP is a challenge.

Paul Sax, MD: You’re not supposed to refill it until you get that next negative HIV test, and it’s been 3 months and then. But I think we have to be a little looser with our follow-ups, allowing people to stay on PrEP without necessarily doing everything that is in the guidelines every 3 months like clockwork.

W. David Hardy, MD: Because another thing we have to realize also is that PrEP is not taken like HIV medications, meaning continually for a lifetime.

Joseph Eron, MD: Sure.

W. David Hardy, MD: PrEP can be taken in fact on and off and on and off, depending upon someone’s sexual activity, depending upon what’s going on in their life, depending on what’s going on in their partner’s life. Now we have to be aware of that and also be flexible to let people say, “I’m going to be off for the next 3 months, so don’t expect to see me. But when I’m ready to go back on, I’ll go back on.”

Eric S. Daar, MD: It’s worth reminding everybody that, as Ian said, it’s tenofovir and emtricitabine. But right now at least, pending more data, tenofovir, disoproxil fumarate, and emtricitabine. So we’re not yet using the new form of tenofovir that we’ve integrated extensively into our treatment strategies. We’re not yet using that for prevention, although there is a study that’s actually looking at that. So hopefully we’ll find out soon.