June 21, 2013
There has been a great deal of talk lately about the most recent addition to the HIV prevention "toolbox": pre-exposure prophylaxis, or PrEP -- taking HIV meds when you're still HIV negative in order to reduce your risk of becoming HIV positive. Much of the focus of conversation and writing about PrEP has focused on gay men; and though Truvada (tenofovir/FTC) is approved as PrEP for all people at high risk for HIV, news regarding PrEP for women has been largely negative, what with several PrEP methods proving ineffective in a large study of women in sub-Saharan Africa.
So what is going on in the realm of PrEP for women? TheBody.com spoke with Valery Hughes, a nurse practitioner who has been providing HIV care since the dawn of the epidemic. Today, she's helping to run a PrEP study just for women -- and it's enrolling now. Hughes shares her expertise and opinions on how HIV-negative women will get PrEP (and what barriers they may face); comparisons between PrEP and birth-control pills; what non-HIV-specialist docs ought to know about PrEP; how far we've come in all areas of the epidemic since the dark days of the '80s; and how far we have still to go.
Having worked in the community providing HIV care for for as long as you have, and now working on this HIV prevention drug study, what do you think the rollout of PrEP for women is going to look like? What do you think will be the most effective way to go about it?
There are a bunch of issues to consider. I think the first is: Should we link any kind of HIV prevention to primary care? I know a lot of physicians are thinking about that. I think it's a great idea, because, of course, the more people we get into primary care, the more we can discuss the full issue of sexual health, including testing and treating for other STIs (sexually transmitted infections) and preventing other viral infections, such as HPV (human papillomavirus), hepatitis B and hepatitis C. But I'm not sure if that's the best idea.
I think that, in my professional heart, I would love to see this linked to primary care. But I can see that there are going to be some obstacles for that. Because I think a lot of women don't have access to primary care. I think we're talking about people with limited insurance, or possibly no insurance. And I'm wondering whether there would be a better way to roll it out with easier access, without so much bureaucracy and without so much money involved, sort of in the Department of Health model.
I think the Department of Health does a great job in STI surveillance and treatment. And it's pretty easily accessible. However, there are some issues with PrEP that aren't there when you do testing and empiric treatment of STIs. Part of that, of course, is the long-term monitoring of side effects. So, there are two ways that I can see it going: one, as I say, linked to primary care; and the other in a sort of more accessible way.
Can you explain the Department of Health model around STI surveillance, and how that relates to PrEP availability?
If a person thinks they may have been exposed to an STI -- if they get a call from their friend saying, "I just tested positive for syphilis; you should get tested" -- you can actually just walk into the Department of Health at any time and they'll test you and treat you right then and there. No money up front. There is a fair amount of waiting around at the Department of Health. But they're very good about that. So it's a great, accessible model.
However, in these cases, they're testing and treating for something that is in existence; PrEP is a different thing because it's trying to prevent something that, of course, hasn't happened yet. And here's the crux of the problem: If you are going to take a medicine for a disease that you have that's going to fix something that's broken, that's a very, very different thing than taking medication for something you don't have yet. And so there have to be more safety tools in place in order to prevent people from having side effects from whatever medication we end up using for PrEP.
Speaking of taking medications to prevent something from happening: What do you think of the comparison that's occasionally made between PrEP and "the Pill" to prevent pregnancy? They both need to be taken every day in order for them to work properly; but is this an apt comparison? What are the points of similarity and difference between these two prophylactic medications?
I think in the ways in which they're similar, they do confer freedom to be sexually active in a less restrictive way. That certainly was, I think, [PrEP consumer and advocate] Damon Jacobs' whole argument in comparing the Pill and PrEP.
But a glaring difference is that pregnancy is one form of consequence of sexual activity, while HIV is one of several -- arguably the worst, some would say -- of all the STIs that can be the consequence of sexual activity. Part of the issue with PrEP is that it's protecting against only one of the possible consequences of sexual activity. So they're alike in some ways, and very different in other ways.
I used to hear all the time that pregnancy could be a serious health risk for a woman. Well, I think that's kind of a silly argument for birth control. I think birth control has all sorts of things to recommend it. But the consequence of getting pregnant is very, very different than the consequence of getting a disease. So I really think that they are, emotionally and in all sorts of other ways, a very, very different kettle of fish.
However, if it's something that you have to take every day -- and women have proven that that can happen -- then I think we need to look at the comparisons in a positive way.
As has been said in commentary on recent PrEP study results, particularly those that proved unsuccessful: PrEP works if you take it -- if people are able to be adherent to it, and take it every day. The recent disappointing results of the VOICE study gave nods to the fact that there are all sorts of different challenges that come up in people's lives that make it hard to adhere to meds -- and we know that's the case even for conditions a person already has. Would you talk a little bit about that?
Using VOICE as an example is interesting, because it does sort of highlight the difference between women in sub-Saharan Africa, where the study was conducted, and women in New York City. They have very different priorities and very different lives.
Another thing about VOICE was that it was a three-arm study; one of the arms was a microbicide gel form of tenofovir (Viread). I think what was definitely part of the issue with non-adherence there was the acceptability of gel. Which is really one of the endpoints of the study: They found that women don't like to use the gel. So that tells the story right there.
But regarding swallowing the pills every day: I wish they had parsed out some of the reasons why women did not take the pills. I understand that they did have a questionnaire in the VOICE study and that, by questionnaire, women were 90 percent adherent; whereas in pill returns and in blood levels, they were obviously much less than that. So that speaks to that whole issue of: Why would you go forward and accept a prescription for a medication, or even accept a bottle of pills, and then not swallow them?
There are two things that occur to me. One is that life in Africa is very different than life here. And a lot of times I've found some of my patients who are from Africa often will take the meds that I give them and ship them home to family members who have HIV. So I think that that could be part of the problem. It could also be that perhaps people just cannot find it in their schedule to take medications every day, when they have a different type of life.
Or it could be that, like all women, they have so many competing priorities that their health comes last. And I think that's probably, for me, the biggest challenge to getting women to take PrEP: Their health always comes last. On the spectrum of things to do, taking care of my health is always at the last. I think that's what happens with a lot of women.
Going back to what you mentioned earlier about potentially incorporating PrEP into primary care: Our community, the HIV-affected community, is clearly the arena where there's the most PrEP knowledge (and the most PrEP conflict), but out in the realm of general primary care, maybe that's not necessarily happening. Maybe there are even misunderstandings about HIV itself, much less prophylactic pills for it.
In an ideal world, what do you think training and education would look like for non-HIV specialist primary care providers about PrEP? And what might it actually look like in the non-ideal world that we currently live in?
Well, of course, in the ideal world, if there's a new therapy we would all get trained; we would all find out about ideal dosing; possible side effects; how to monitor; how to assess adherence; how to assess for other sexual health issues. It would be a whole day event, I think.
But in the real world, I think the big take-away would be that PrEP has to be combined with frequent HIV testing, at least every three months, and periodic renal monitoring if we're going to use Truvada (tenofovir/FTC); and possibly even bone density monitoring.
I think we don't have the answers to those questions about what is the ideal way to monitor people who are on PrEP, and I'm hoping that further studies will help to clarify that. But once again, you want to make sure that people are getting tested at least every three months because you don't want people to be on substandard HIV treatment if they do, in fact, become HIV positive while taking PrEP.
If there was one key point that you would want a provider -- someone who may not have PrEP be a regular part of their practice, but might have one or two patients that they'd consider referring -- to take away from their hypothetical, brief PrEP training, what would that point be?
I guess probably the most important one would be the frequent HIV testing; that would be the first one. And the second would be monitoring for side effects. So, periodically get them in and look at the creatinine. See what's going on there and see what's happening with renal function.
One of the things about tenofovir is that it's a great drug until it's not a great drug. And then if the person happens to be one of the very, very few that are affected by it, in terms of a little damage to the kidneys, then it's one of the things you want to catch early. Every drug has warts; even aspirin has warts. So we have to really pay attention. We can't just be writing prescriptions out without any kind of follow up.
PrEP is often talked about in terms of: How are women going to take this every day for the rest of their lives? But I once heard an expert speak on a panel who referenced PrEP as being very useful for "seasons of risk," which I thought was an interesting way to think about it. I'm surprised at how infrequently PrEP is mentioned, at least publicly and in the literature around PrEP, in the context of being a potential temporary prevention method for women who are with HIV-positive male partners and are trying to get pregnant. Could you speculate as to whether it could be an alternative to some of the other methods of getting pregnant that discordant couples may already be employing?
I know, seasons of risk: that's kind of an interesting concept. I have had discordant couples in my practice, where they did sperm washing and in vitro to get pregnant, where the woman was negative and the man was positive. If taking PrEP were a reasonable thing to do it would be certainly a lot cheaper than in vitro. I had one patient who spent lots and lots of money trying to get pregnant. She did finally get pregnant. But for the second one, she was unable to conceive the second and third time she tried -- and spent a lot of money trying to do that, and was very committed to the process.
Would that be a reasonable alternative? I don't think there's any way to know if that's a reasonable alternative, frankly. I can't really look into my crystal ball. But I think that ultimately people may end up thinking about that.
You know, both tenofovir and the drug that we're studying in HPTN 069, maraviroc (Selzentry), are both category B. And what that means is, who knows? Nobody knows. So, how long do you take it after you try conception? It's a very good question. That's a definite unknown. That's a very interesting question.
Please talk about the PrEP studies that you've been involved with at Cornell. What other meds are you looking at? How was it decided what different medications would be tried now that the concept has been proven with Truvada?
The study we're running is called HPTN 069. It's our first prevention study at Cornell Clinical Trials. And this study compares the standard of care, Truvada, against a newcomer to the prevention arena. Its name is maraviroc. That drug was developed to block a coreceptor in the human cell called the CCR5 coreceptor. And it's required that you have to have that coreceptor in order to complete attachment. The virus needs it to complete attachment in order to complete infection.
It was developed as deep salvage therapy for people who had failed other antiretroviral therapies -- obviously, for people who were infected. So it's been looked at. I think one of the reasons why it's so interesting is because this drug achieves very much higher levels in rectal and vaginal fluids than it does in the blood. That could partly be because it's attached to the lymphocyte; and lymphocytes are hanging out in those areas. But, for whatever reason, it's there. And that's the point of infection. So in some ways it seems kind of intuitive to use a drug like that.
In any case, HPTN 069 compares, once again, Truvada -- in this case, everything is given in separate pills, so it's not really Truvada, it's a component of Truvada, which is tenofovir and FTC. So you have three pills: maraviroc, tenofovir, FTC. And it's a double blind, randomized study, where you don't get to choose what you're taking. You get assigned, as though by a flip of a coin. So I don't know what meds you're getting, and you don't know what meds you're getting. Everybody's getting an active drug of some sort or another.
And so the arms are: the maraviroc, or Selzentry, alone; the maraviroc plus tenofovir; the maraviroc plus FTC; or tenofovir plus FTC ... which is, once again, Truvada, or the standard of care. So it looks like three pills once a day. And there are some built-in adherence measures, such as a pillbox called the Wisepill that, when it opens, it sends a signal to a computer and downloads the date and time that it's been opened.
There are some sexual activity measures. Because there's always the question of, when you put people on PrEP, do they throw away the latex, or do they continue to use it, or ... what's going on here? So they're trying to correlate those two things. There are tolerability measures, in terms of interviews that are done at every visit and questionnaires that are done on the computer.
All those things are built into the study. Each individual is on the study for about a year. And all the medication, of course, is provided, all the physical exams and blood tests. However, we do test for HIV a lot more frequently than in the standard of care; we do it at every visit, basically. So it really ends up being a lot more than every three months.
So, that's the study. And it certainly is open and enrolling right now. It's enrolling kind of nicely.
What are the enrollment criteria? Is it women who are in relationships with people who are positive?
Well, you have to be having some sort of risk for HIV. So either you're in a relationship with somebody you know is positive, or don't know, or having sex with people whose HIV status you don't know, or do know that they're positive. So there has to be some sort of risk involved.
A woman would have to be HIV negative, obviously, to start with, and could never have received an HIV vaccine. So anybody who had participated in any of the vaccine studies would not be eligible because it would sort of muddy the waters in terms of trying to figure out about antibody status.
The other kind of perplexing thing for me is peanut and soy allergies. I actually had somebody in my office and it turns out that he was very allergic to peanuts and soy, so I couldn't proceed with the screening. If you're highly peanut allergic, this is not the study for you.
Is it something in the maraviroc? What is it that could activate that?
Yeah. Something in maraviroc, yeah.
Wow. Oh. Who knew? OK.
It's probably a soft finding. But it's one of those things; you don't want to play with people's allergies.
What are some of the challenges for women participating in a PrEP trial, and how have you addressed them in the implementation of this study?
I think that, in general, women have competing priorities. I mean, who doesn't? Even a working woman has to do the shopping, the cooking, the cleaning, and all of that -- at least to some degree. So a lot of women are just saying, "Oh, gosh; I'll do this another time," or, "I'll worry about this later," or, "I can't deal with it right now. I have to make sure my kid gets into so-and-so school, or that my kid gets to his or her doctor." So I think that that is a very, very big issue, not just for this study, but even for studies in women who are HIV positive ... and even regular health care for women who are HIV positive and might have an addiction issue, or might have any other kind of issue. When you have complicated, chaotic lives, taking care of yourself is really a challenge.
I think another one would be a possible backlash from partners. "Why do you have to take this PrEP? I know I'm HIV negative." And what if it turns out that her main partner is not her only partner, and she doesn't want to disclose that? So I think that there's that possibility. And some women just say, "Oh, I don't want to get into that drama. I'm not going to do it."
I think another really big one is the lack of connection to the issues of HIV and sexual health, in general. When you're talking about HIV-negative women, there are a lot of women who don't even know what their risk is for HIV, basically because in the United States sex is still such a taboo subject in places where women might learn practical ways of staying healthy, such as schools, even TV -- although, I have to say, I see some of these shows that talk about sexual health, like The Doctors: They're definitely getting better about talking about these things in a reasonable way. But I think that TV, and media, in general, still sort of snickers about sexual health issues. They're not treating them in a straightforward and adult way. So there's still a lot of stuff out there that is preventing people from coming forward and saying, "Hey, I'm a human being. I'm a sexual human being. Let me do what I can do to stay healthy."
Remember what it was like to try to roll out Gardasil for HPV prevention -- how much backlash there was, just for that? "Oh, my God! You want me to give this to my 12-year-old? That's like saying they can go out and have sex!" People took such a leap. So I know that there are still an awful lot of problems in terms of taboos and prejudices. And I think that that is something that we're going to have to work on. So I think that, in many ways, the odds are stacked against young, sexually active women to try to keep them ignorant, for some unknown reason.
And then, of course, young, sexually active women are often very busy women. They themselves don't have the time to start to look into this. So I think that we're going to need to go beyond traditional ways of educating women. I think that in some ways you have to avoid bureaucratic obstacles with schools and churches, and reach the women the way we've done from time immemorial, which is woman-to-woman.
One of the things I'd love to do would be to blanket hair and nail salons with posters and flyers; have posters in shops and on subways and buses; and in movie theaters and restaurants; blanket the Internet. But all of this stuff costs money.
The other thing I would love to do is to try to target and encourage professional sex workers to at least come and have a conversation with me, and see what there is I have to offer. I think that, in general, people who are sex workers, women who are sex workers, often feel very disenfranchised, and also feel very much like they don't want to engage health care providers because they feel like they're second-class citizens, in some ways -- which is certainly not the case. And if there was any message I could get out there, it's that this is a really important thing. Sex work is a reality; we have to address it. What are some of the possible complications?
I imagine that there may likely be some reticence to engage with any kind of institution if you're involved in commercial sex work. And if a sex worker wants to join a study and she says, "This is what I'm doing and I'd like to be in the study," maybe there's some concern or fear that whoever's running the study would not be sympathetic to her work situation, and might even call the cops.
I know. It's just very upsetting to hear that, because I know that somebody is telling these women that. And, you know, I think for the most part, often commercial sex workers have people who help them to work, who are actually getting paid the bulk of the money. I'm not saying the P word; but I'm just saying that a lot of times, these people are kept in the dark about what's good for them; because people don't always have their best interests at heart.
But for any professional sex worker who wants to be in the study, I absolutely welcome them. I would love to be able to reach them to have conversations about sexual health in general; and I think that they could help elucidate how we use PrEP.
What's your background and history of working in the HIV community? How did you come to be working on this study, in particular, and with PrEP?
I'm a nurse-practitioner, and have been since sometime in the late '90s. But I've been a nurse forever -- since 1976. And when HIV came along, we didn't even call it HIV. It had some ridiculous acronym -- GRID was one of the ones. There was all sorts of stuff going on.
Basically in 1980 was, I guess, the first case that I am quite sure was HIV related, even though it wasn't recognized at the time. But in retrospect, I see that. And when the full-blown epidemic hit New York, I was working in a New York hospital (not where I'm working now, but in a major New York hospital) and I saw the things that people saw back then: People would come in, be horribly, horribly sick, and die alone, because nobody would go in the room. They were all afraid it was contagious, airborne. And so you couldn't get anybody to bring in a tray to the person so they could eat something, much less go in and visit. And you had people who really didn't even want to work with people with HIV because they thought it was that contagious.
The other thing was that in the very early years, medicine really didn't have a huge amount to offer. HIV was what I called a "nurse's disease." The nurses who were willing to could ameliorate what was transpiring, in terms of offering comfort and pain management and symptom management, and all the things that nurses do. So in the first few years, before there were any medications, there were nurses who were in the forefront there. And I was one of them. It was my community, and so therefore I felt very much beholden to them, and very much that I needed to take care of them. And so that's where I got my interest in HIV.
Then, as the years progressed and I became involved even more, I later went on and became a nurse-practitioner. The reason I did that was so I could provide primary care to people with HIV. That was my overwhelming concern: to deal with the illness and try to do the best I could for as many people as I could.
I worked at Lenox Hill Hospital for many years in their primary care unit. And I've been at Cornell since 1999, and worked with Drs. Trip Gulick, and Marshall Glesby, and Tim Wilkin on all of the studies that we've been doing.
In 1999, we were giving ... how many pills was it? Ten pills, twice a day? Sometimes four pills, three times a day. I mean, some of the regimens that we came up with, including my all-time favorite, Crixivan (indinavir), which was every eight hours, two hours before eating and one hour after eating: It was just nuts. We actually went from that to having three regimens that are one pill, once a day, in the last 14 years. So research has definitely been a great place to be for the last 14 years.
I think that in many ways therapeutics has come a long way. But it is really time to get to prevention, and it's time to get to the cure. We need to change our focus. So when the chance to work on this study came along, I jumped at it, because I thought, oh, gosh; this is great.
So they originally rolled out the male cohort. And they just very recently opened the cohort for women. So I'm really excited about that.
Judging by your extensive experience working in this epidemic, what do you believe will be the effect, or the ongoing role, of PrEP in the epidemic as a whole? Do you think that it has potential to make a real dent in the number of new HIV infections? What would it take to get there? Or will it stay a kind of niche item for people who happen to have access to knowledge about it?
I don't know. I have two thoughts. I'm not a statistician, so it's really hard for me. It's a real loaded question for me. I'm hoping, in my sort of non-statistical way, that PrEP can decrease the overall number of people with HIV over time. I mean, if, every year in the United States about 50,000 people are getting infected, what if that got cut to 10,000 people? What would that do to the progress of the disease over time? I can't tell you the numbers, but I know that that's the goal.
But when I think about it, I can't think in those large terms. I'm really kind of a bird-by-bird person: You've got to count one thing at a time; one infection, and one person, at a time. That's how you have to be in research. It's kind of odd. People think that clinical researchers are looking at big-picture stuff. But really, we're very detail oriented. And I'm always one-person-at-a-time.
So my hope is that I'll turn around in a few years and I'll say, "Oh, my goodness. What happened?" It's like the same amount of surprise I had when I turned around after 14 years of working here, then we went from eight pills, twice a day, to one pill, once a day. I said, "Well, I guess we did do a good job!" I'm thinking that that's probably going to be my response -- that I'm going to be a little bit surprised because I didn't see it. I was right in there with the trees; I didn't notice the whole forest was actually coming down. That would be a great thing.
On a similar vein, judging by what you mentioned about your history in the community, you were around and working in HIV at the time before and after effective treatment was introduced, and people started to realize: "It's been a while since I've been to a funeral," or, "It's been a while since I've lost a patient" -- as opposed to hundreds, on a regular basis, due to AIDS complications.
It's been very interesting. And you're right: that was a huge time. That's why I mentioned the Crixivan because, as much as we hate that drug, it saved so many people ... to keep them going until the next better thing came along. It was definitely what I would call a bridge drug. But I was there when 3TC (Epivir, lamivudine) came out ... I was there when all the drugs came out. I have been able to see the effect of all this work -- both on a community level, working in primary care on a community level, and being a gay person; and on a professional level, working in research. So it's been a huge, huge, big change.
I think PrEP may be the next sea change that we have. I'm hoping it will be. Ask me in a few years. I'll look back and say, "Oh, darn. That was a good idea, wasn't it?"
But I also think it's only one part of trying to get rid of HIV. Because I think the other part of it, of course, is trying to find the cure for people who are already infected. And that stuff is being worked on. I'm not working on it, but other people are. And it's one of the things that has to go forward, and that I support.
PrEP is just one tool, if you will. People love to talk about that toolkit. It's one tool in the toolkit. It's just part of what I'm hoping is going to develop into comprehensive sexual health. And I can't wait until people get the memo.
Everybody has sex. Nobody wants to talk about it. Everybody does it. And we just need to figure out how to stay healthy.
This transcript has been edited for clarity.
Olivia Ford is the executive editor for TheBody.com and TheBodyPRO.com.