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Get PrEPared: The Low-Down on PrEP and HIV Prevention

By L. K. Regan

We recently talked about PEP, or post-exposure prophylaxis: a month-long course of AIDS medications administered to someone who thinks he may have been exposed to HIV within 72 hours of that exposure. We spoke to Dr. Raphael Landovitz, MD, an Assistant Professor in the Division of Infectious Diseases at the Center for Clinical AIDS Research & Education at the University of California, Los Angeles, who is a leading expert conducting research on PEP. This week, we follow up with Dr. Landovitz for a discussion of PrEP, or pre-exposure prophylaxis. He gave us the run-down of the pros and cons of this controversial protocol for people who are HIV negative but at very high risk for HIV infection.

What is PrEP?
PrEP is a continuous course of AIDS medications, administered to someone who is HIV negative but engages in high-risk behavior to prevent him or her from contracting the virus in the event of exposure. As Dr. Landovitz puts it succinctly, "PrEP is like being on a birth control pill, where you take it every day regardless of whether you think you will have sex that day. PEP (which we talked about last time) is like a morning-after pill for people who think they've just been exposed to HIV. "

But, of course, HIV meds have the potential to be considerably more toxic than the birth control pill. But there are other differences as well between conventional HIV-treatment and PreP: People who take PrEP don't take a standard three-drug HIV protocol on a continuous basis; they will instead take one or two drugs at a time. Currently, the PrEP protocols are in clinical trials: while it seems promising that it would work, it actually isn't yet known whether PrEP is effective in preventing transmission of HIV. As we will see, the question of efficacy is only one of the thorny issues surrounding this highly controversial treatment.

Why PrEP?
This may seem like an obvious question, but why would anyone need PrEP, anyway? After all, the condom is, as Dr. Landovitz points out, "Over 90 percent effective in preventing HIV transmission when used correctly and constantly. And, condoms also prevent against pregnancy and STDs while they're at it." So why don't we all just use condoms? Because, Dr. Landovitz says, it turns out that just getting people to put on a condom is a pretty seriously complicated social task. "Getting people to change their behaviors is one of the hardest things in all of medical science—to use condoms, or think through that decision tree at the moment of intercourse, or think through the risks of needle sharing for IV drug users—is really tough. There have been lots of developments in getting people to change behaviors a little bit—but they've been small and incremental. To stop a worldwide epidemic you need a more radical intervention. Now, the condom is a radical intervention—but getting people to use them regularly is very challenging. Gay men don’t like to use condoms and in some parts of the world women are not empowered to ask their partner to use a condom, for reasons of culture, or distrust of partners, or because it reduces pleasure. And of course, in cases of sexual assault or domestic violence condoms aren’t used most of the time. So there are lots of complicated psycghological and social issues tangled with base desires that make the condom a difficult tool if it’s going to be the only one we have for HIV prevention."

For a number of years, therefore, researchers have been searching for additional ways of preventing HIV transmission, with a number of technologies being developed simultaneously:

  1. A vaccine: "The Holy Grail is a vaccine," Dr. Landovitz says. "If we had a vaccine, a lot of these other conversations would become secondary. But we’ve had little success in developing a vaccine so far. HIV is an incredibly smart virus that evades the immune system and changes in response to all immune system efforts to destroy it. We have a rudimentary understanding of how the virus interacts with the immune system, and we need a lot more than that to understand how to create a vaccine. So we’re really far away from having a preventive vaccine—maybe as far as we were 10 years ago when we said we might have a vaccine in 10 years."
  2. Microbicides: Lately there is a lot of talk about microbicides. These are topical creams or gels inserted at the time of intercourse and that inactivate the virus while acting as a lube and a contraceptive. The ideal microbicide would have many advantages, Dr. Landovitz says: "They would be easily applied; they can be kept secret from a partner, giving the receptive partner control—no complex negotiation or breaking the mood—and they are, ideally, odorless and tasteless." They are also an idea that's been around for a while, with limited success. "A couple of exciting products in the pipeline had really disappointing results when studied," Dr. Landovitz says, "especially nonoxynol-9 spermicide in condoms. Not only does it not protect against HIV infection, but it actually increases risk by irritating the vaginal or rectal lining. That inflammation allows HIV to cross." Other compounds (cellulose sulfate, for instance) met with similarly disappointing results in clinical trials. But, Dr. Landovitz says, new research holds promise for microbicides. "Just recently research on a microbicide called PRO-2000 has found an approximately 30 percent reduction in HIV transmission with heterosexual couples where the man was positive and the woman negative. It's unclear as yet whether the numbers will hold up, but it’s a first proof of principle that this kind of technology might work."
  3. PEP: Post-exposure prophylaxis remains a highly effective option — likely more than 80 percent effective in preventing transmission in the case of the accidental slip-up. But, as Dr. Landovitz pointed out in our recent piece on PEP, the hurdles to its use are substantial, ranging from the difficult of accessing it, to the expense of the treatment, to the length of time one must remain on the medications. In short, while PEP is a very good option for those who have only one high-risk encounter and who can access the treatment, it is not for everyone and is not easily available.
All of these delimiting factors mean that other kinds of interventions in HIV transmission are still being developed, and that there is plenty of room to find more ways to inhibit transmission of the disease for those who do not succeed in successfully using condoms, or who want additional protection in case a condom breaks or fails.

  • Enter PrEP
    No one is suggesting that PrEP is for everyone. Again, as a first line of defense (and in the absence of a vaccine) it is impossible to beat the condom, which is inexpensive, easily available, easy to use, and does not have any secondary health consequences deriving from its continued use. PrEP is expensive, requires substantial commitment, and may eventually take a toll on a patient's health. Additionally, no one knows how long it would need to be taken before it’s effective (a single “disco” dose? Two doses? A week? Two weeks?), nor how long someone should stay on it. So who would get this treatment?

    PrEP is a potential option for two kinds of people: those who cannot protect themselves by other means, and those who have a track record of not protecting themselves by other means. In other words, in the developing world, PrEP could potentially be an option for women who are not in a position to refuse sex to an infected partner and whose partners may be unwilling to wear condoms. Likewise, think of guys who have high-risk sex and, perhaps do a round of PEP—and then go right back out and slip up again. While working on ways to get them to change their behavior (which is a difficult and slow process), it might be a good idea to try putting them on medication all the time to protect them in the meanwhile.

    PrEP Problems
    The former case—of the woman whose environment will not let her control her sexual choices—easily wins sympathy, but in our culture thorny moral issues cling to the second example. For one thing, if people feel that they are protected by PrEP, are they going to feel liberated to have yet more high-risk sex? And what does one think about the fact that if they do, they are likely to get a drug-resistant strain of the virus, which will be much harder to treat (in addition to increasing the prevalence of such a viral strain in the population)? In short, do we want to encourage the development of PrEP, if PrEP will in turn encourage this kind of licensed behavior?

    Dr. Landovitz has some serious gripes with such arguments. "These were the same arguments," he points out, "used about birth-control pills to squash the feminist movement." In fact, he says, a major part of PrEP research has gone into investigating the effect of PrEP on people's sexual behavior. "The media was incredibly sensationalistic about PrEP—saying that guys were going out mixing Viagra and Ecstacy and an HIV drug at the same time in the clubs and taking this as license to have high risk sex. It got a lot of press in 2004 and 2005. So two research groups—Al Liu in San Francisco and Scott Kellerman in New York—set out to investigate. And they found evidence that the vast majority of gay men had never heard of PrEP or such 'disco dosing', let alone participated in it. So it's really unclear to what extent this really was happening in the community." That all being said, it would be a complete disaster for HIV prevention if in fact people thought they could pop the PrEP pills and go out and have more high-risk sex: Mathematical models of the HIV epidemic show that even small increases in the rates of high-risk sex could have a big impact on increasing the HIV infection ratesf—because remember, even if PrEP works, at best it’s not going to be a perfect 100 percent effective intervention.

    The issue of drug-resistant strains of the virus is much more pressing, in Dr. Landovitz's opinion. "We're still waiting for research to show the safety and tolerability implications of being on these medications when you're not positive. How much is enough? Once a week? Once a day? No one really knows. So people on these drugs need close and careful monitoring, not just for toxicity but also for infection. Because if they do get infected while on the drugs, the virus they get infected with could be resistant to the PrEP medications." In other words, do not try this without the supervision of an expert physician.

    There is a final complexity surrounding PrEP that Dr. Landovitz feels should be a serious caveat to its widespread use. This is a matter of how AIDS treatment is represented by pharmaceutical companies and thus perceived in the community more broadly. "As HIV meds have gotten better tolerated, a lot of the toxicities of HIV treatments have become less of an issue—they're still there, but nowhere near what they were ‘back in the day.’ Pharmaceutical industry ads show HIV positive people hang-gliding, sailing—and that’s terrific, because these medications do save lives; however, the ads minimize the impact of taking meds. So I fear there’s a perception among young, sexually active gay men that weren’t around in the old days of the epidemic, that it’s not a big deal to get HIV. Anyone advertising these drugs in this way does a disservice to the community, because even though AIDS treatment has gotten better, it's still not something you’d wish on someone."

    In short, a condom is still, in the end, the very best option. As Dr. Landovitz weighs the various options, "PrEP is potentially exciting for parts of the world where for example, women don’t have right or ability to refuse sex or unprotected sex. Or for people who use condoms, but want an extra measure of protection on top of that. So, put this with PEP and circumcision and microbicides as one on a menu of options that may help to reduce infection in different combinations in different populations, but where we really need to understand how they will work and where each will be the best solution." For the U.S., the future of PrEP needs to be kept in perspective. "If PrEP proves effective in clinical trials," Dr. Landovitz says, "people will be very excited to use it. But we need to be very clear that it will never be an alternative to condoms, and no matter what the studies show should absolutely not be thought of as an alternative to them. Rather, it may, if serious clinical trials pan out, be a potential supplement to condoms."

    In short, the condom is still the most effective method of preventing HIV infection. Go out and buy some fresh ones now, while it's on the top of your mind.