LETTERS From CAMP Rehoboth |
The Morning After? Post-Exposure Prophylaxis Raises New Issues at the Crossroads of Treatment and Prevention |
By Sean Bugg NASTAD HIV Prevention Communications Specialist |
For years now, health care workers who have been exposed to HIV through a needle stick or other route have had the option to undergo medical treatment in hopes of blocking HIV infection: post-exposure prophylaxis (PEP). But it has only been in recent months that the idea of providing this type of treatment for non-occupational exposures has gained a foothold in the outlook of HIV prevention. For example, in June of last year, Time ran an article by Christine Gorman on the so-called "morning after treatment," linking its emergence with the excitement about recent successes in the treatment of people with AIDS. "The fact that morning-after treatments are being discussed at all shows just how far HIV drug therapy has come in the past two years," Gorman wrote. "[S]ome scientists believe that if the virus is caught early enough in the cycle of infection, it may some day be eradicated from the body. Why not hit the virus immediately after the first suspected exposure, thus wiping it out before it manages to get a foothold?" [Time, June 23, 1997, p. 48] Amidst this excitement, a number of voices have claimed that embracing PEP entails many pitfalls that could hinder, or perhaps even damage, HIV prevention efforts. Is PEP really effective? Will our target audience abandon healthier behaviors in the misguided belief in a morning after cure? And who decides, if anyone, which people get access to this expensive treatment? Does it work? Although there are some limited studies currently underway regarding non-occupational exposures, such as sexual, there are no data as of yet regarding the effectiveness of PEP in those situations. The current discussions about PEP all revolve around data collected and analyzed in studies of health care workers occupationally exposed to HIV. According to CDC, a 1994 study of surveillance data from health care workers in three countries, including the U.S., showed that although failures occurred, the use of AZT for post-exposure prophylaxis was associated with an approximately 79% decrease in the risk for HIV infection after percutaneous [i.e. under or through the skin] exposure to HIV-infected blood. In June 1996, CDC released recommendations on the use of PEP for HIV exposed health care workers. For those at highest risk of infection, such as a health care worker who receives a deep injury with a large diameter hollow needle previously in source patients vein or artery, a triple combination of AZT, 3TC and a protease inhibitor is recommended. Depending on the assessed risk to the worker, the recommendations range from "recommending" or "offering" PEP, to not offering treatment. Although the recommendations and the data that fueled them have played an important role in the current discussion of non-occupational PEP, its important to remember that the risk of infection for a health care worker is low, with a risk of infection after all types of percutaneous exposure to HIV infected blood of approximately 0.3 percent (American Journal of Medicine 1997; 102(5B):9-15). Also, workplace safety procedures help keep the risk even lower by avoiding any exposures to HIV. As of June 1996, only 51 documented cases of occupationally acquired HIV infection had been reported in the United States, along with 108 reports of possible cases. "Exposure to HIV is uncommon, but if exposed, being offered such therapy [as PEP] is common," said Dr. Dawn K. Smith, Medical Epidemiologist at CDC. So the data indicate that there may be some positive effects from the use of PEP to help block a new HIV infection. But even within the studied realm of health care workers, the data is not definitive. "Theres no evidence from animal or human studies that theres any post-exposure regimen that would be a hundred percent effective, that would reduce the risk of transmission to zero," said Smith. This becomes more problematic when the health care worker data is applied to sexual or other non-occupational exposures. The risk of HIV infection from an instance of unprotected anal sex with an HIV infected partner can range from approximately one to three percent. And while on the surface it may seem logical to assume that one HIV transmission works like any other, thats not necessarily the case. "We dont know whether it applies," said Smith. "Some people make the assumption that it probably does. But we have lots of things in science that seem to make sense but turn out not to be true. While I think its reasonable to say that if it works in one setting it probably works in another, you dont really know that." CDC does not plan to issue guidelines or recommendations on PEP for non-occupational exposures. However, a Public Health Service working group is developing a statement on the treatment - the statement will not set any standards for care or treatment, but is expected to present what is known and not known about the effectiveness of PEP and offer information on current practices. However, current practices for non-occupational exposures vary and different programs and clinicians prescribe different drugs for PEP. Still, as people with AIDS who take triple-combinations of protease inhibitors and other AIDS medications know, the side effects can be significant. Some people who undergo a 28-day PEP regimen may experience diarrhea, cramps, fevers and other side effects. And on top of that, that person may also be pay upwards of $1,000 for the treatment. Among those interviewed for this article and others in the field, there is near unanimity on one aspect of PEP - if its going to work, it has to start early. The outer time limit from the time of the exposure ranges from 36 to 72 hours, but the earlier the treatment begins the greater any chance for success may be. Its a matter of hours, not days. Whats in a Name? Participants in CDCs July 1997 consultants meeting on Post-Exposure Prophylaxis for non-occupational exposure to HIV arrived in Atlanta to find that the topic of discussion had changed somewhat. The subject at hand was PET, or Post-Exposure Therapy. The change in terminology may seem slight, but as in many other areas, small changes to a name can mean big changes in the underlying concepts. Or, at least, thats often the goal. If you call it post exposure prophylaxis that assumes that what youre doing is actually known to prevent infection, and we dont actually know that it does prevent infection in these instances,@ said Dr. Smith. IF you say therapy, sometimes therapies work and sometimes they dont, but they are an attempt to deal with a health threat. There are other people who feel that management is more appropriate because both prophylaxis and therapy suggest medications alone, whereas the issue of risk reduction for persons who have exposed themselves to HIV is better reflected in management. I think it also reflects a concern about the lack of information we have about the effectiveness of these drugs.@ The different terminologies that come into play regarding PEP reflect the greater concerns about the role this medical intervention plays in HIV prevention. Both in concerns voiced at the CDC consultation meeting and in subsequent publications and discussions, those who work in HIV prevention worry about another label that PEP has received in some media stories: the morning after pill. Of course, this label has been used before in many contexts, perhaps most recently when pundits, politicians and others quickly attached it to the abortion drug RU-486. And in the case of both HIV and pregnancy, the misnomer can cut both ways. First, it can provide a false sense of security for those most at risk for infection (or, even, unintended pregnancy). And second, morning after pill carries an unmistakable connotation of irresponsibility, of putting oneself at risk in the frivolous pursuit of pleasure. Controversies surrounding a pill, pills or behavioral/medical interventions aimed at reducing the unintended (negative) consequences of sex remain part of the backdrop of our nations pressing health crises, writes Mike Shriver, Deputy Executive Director for Policy of the National Association of People with AIDS (NAPWA), in a soon-to-be-published paper. And these background biases can work their way into media reports about PEP. For example, the Time article mentioned earlier opened with an anecdote of a "30-year-old Bostonian [who] knew he was taking a chance when he visited a bathhouse for a homosexual tryst. It wasnt until the condom broke and he saw the blood and blanched." The message contained in this and similar stories is a somewhat moralized criticism of the behavior that leads to the necessity of treatment to block an HIV infection. While the man in this story had apparently used a condom, use of the phrases "taking a chance" and "homosexual tryst" show a bias against the behavior itself, regardless of the protections he had taken. Poz magazine recently took a different tack in an article on PEP. That article opened with the tale of a man who, while on a cocaine and crystal meth binge, was sexually assaulted at knife point by another man (who he picked up on a phone sex line) whose stated intent was to infect him. The mention of these stories is not to downplay the serious nature of the situations these men found themselves in, but instead to highlight the tone that coverage of this issue has often taken. This is especially important when you approach the next question about PEP: Who, exactly, is it for? Judgment Calls One place in which many people see a potential benefit for PEP is the hospital emergency room, often the front line of treatment for victims of rape and sexual assault. The Massachusetts Department of Public Health AIDS Bureau is currently working with two pilot PEP programs, one of which is located in the emergency room of Lawrence General Hospital in Boston. "It was selected as a pilot site because it is the only site in the State at the moment that has a State-funded sexual assault nurse examiner program," said Jean McGuire, Massachusetts AIDS Director. "That capacity suggested that they might be more likely to be able to handle providing a new protocol in an appropriate manner." McGuire says that the pilot helps address the dilemma many emergency rooms, as well as other providers, have found themselves in. The PEP protocols for health care workers are well known by emergency room staff, and when presented with a patient who may have been exposed to HIV, they ask: Do we provide the patient with the same treatment we offer health care workers? "You can have a victim of a multiple assailant rape that happened in a drug related environment, and in the city of Boston you would be concerned about likelihood of exposure to HIV," said McGuire. "Or rapes that occurred in the prisons or other circumstances. "So you have this real moral clinical dilemma operating within the emergency room environment. We have data thats suggestive [of PEPs benefits], but is not proof positive. I think what has made this last year different is a surge of both belief and hopefulness from the good results from treatment-related data." Its not uncommon for victims of sexual assault to receive prophylactic treatment for a number of different conditions, including pregnancy and sexually transmitted diseases. However, providing PEP is much different. Unlike the other treatments, a course of PEP lasts for 28 days and judging the risk of HIV infection is difficult when the serostatus of the attacker is unknown. The process includes risk stratification, similar to how CDC organizes occupational exposure assessment as high or low according to the nature of the needle stick and the circumstances of the source patient. "Theres a similar kind of discussion that proceeds here," said McGuire. Obviously, did they know the status of the assailant? If they dont know the status of the assailant, do they know the assailant to be a drug user? Theres a discussion with the patient and ultimately a decision that the patient makes in combination with the clinician. The nurse clinicians are pursuing an assessment of the exposure that they frankly would be pursuing anyway in the course of recording the nature of the sexual assault, with a bit more attentiveness to other pieces of the environment that might raise concern or suspicion about HIV exposure. But some have raised concerns about the ability of sexual assault victims to make informed decisions about PEP in the short time following the assault. Paul Kawata, Executive Director of the National Minority AIDS Council (NMAC), said that although his organization has not developed any official policy regarding PEP, his own experience with victims of sexual assault and domestic violence highlight these problems. "A person who has suffered sexual assault through rape or domestic violence should have [PEP] treatment should he or she desire it," said Kawata. "However, in my experience, the time lapse between when the assault occurs and when the person is able to make a reasoned decision about going on treatment is too long." "When a person is assaulted," he said, "there are other issues that come first. Emotionally, as well as physically, theres a lot of other damage. One of the things Im more concerned about is that we have appropriate services to meet those needs for people who suffer sexual violence." Another major area of concern about non-occupational PEP is its application for HIV exposures arising in consensual sexual situations. Aside from the implications it has for the broad HIV prevention messages, which is discussed further below, in what situations might PEP be an appropriate treatment? The Fenway Clinic in Boston has been offering non-occupational PEP for gay men for more than a year. And in San Francisco, the Centers for AIDS Prevention Studies (CAPS) and the San Francisco Department of Health have implemented a research program to study the "safety and feasibility" of PEP. In a statement announcing the program, Thomas Coates, PhD., director of CAPS, said, "It is important that people understand that this study is not to examine whether post-exposure treatment is effective; that will need a much more complicated long-term study." "The aim of this study is to determine the characteristics of individuals who are exposed to HIV, to look at what kinds of post exposure prevention practices they follow and whether they comply with their treatment regimens." Compliance with treatment regimens, also called "adherence," is an important issue in both PEP and the treatment of people with HIV/AIDS. By taking the new treatment regimens irregularly, the possibility exists of creating resistant strains of HIV that would greatly decrease the efficacy of the current class of drugs, decreasing the high level of treatment success seen in the past two years. NASTAD Chair Randall Pope said at the CDCs PEP consultants meeting, "We [should] take note of the lessons recently learned from frequent and inappropriate use of antibiotics which have resulted in the emergence of resistant strains of bacteria that now threaten the health and safety of many of our citizens and health care providers." According to the CDCs Dr. Smith, developing resistance isnt the biggest problem that a person who undergoes PEP may face. "If they are truly exposed and a few cells have become infected, and they only take the drugs now and then, yes, theres a risk they will develop a resistant strain," she said. "But that risk is very unlikely. Resistance is not something that happens in a day or two. So the likelihood that, on a short course, they are going to develop resistance because of non-adherence is pretty slim. "But what could happen is if they have truly been exposed, and the person to whom they were exposed has developed resistance to certain drugs, and you put them on the same drugs, then they may acquire that persons drug resistant strain," she said. Also problematic is determining in which cases PEP may be warranted. Dr. Douglas Ward, a Washington, D.C., physician who specializes in internal medicine and HIV/AIDS, has prescribed the PEP regimen twice. "One time I did prescribe it was for a patient who was simply making out with someone, noticed a funny taste, and it turned out the other guy had a major nosebleed so that this guy got a mouthful of blood," said Ward. "His partner said, Weve got a problem, Im positive. This patient called me on a Saturday afternoon, and I had him on medication within an hour." Ward said a number of factors should be considered when someone presents with a sexual exposure to HIV, including the exact route of transmission (was it oral or anal, receptive or active?), if the serostatus of the partner is known, and whether the patient knows his own serostatus. He also noted that individual sexual acts, taken by themselves, carry a low risk of infection. Its repeated exposures over time that will significantly raise the risk of infection. The idea that people may repeatedly engage in unprotected sex with the idea that a "morning after pill" can protect them from infection is perhaps the most frightening for prevention workers concerned about PEP, particularly since even if PEP is effective, its certainly not 100 percent effective. Studies and programs currently in place, including the Fenway Clinic and the CAPS study, have included an intensive focus on helping patients make and maintain healthy behavior changes. What price prevention? Those who think they have been exposed and are considering whether or not to undergo PEP may have the decision made for them by another important factor of this therapy: cost. The new class of AIDS drugs have proven incredibly powerful, and the results have been so astonishing as to make the high price appear, perhaps, as a bargain. Whats $1,000 or more a month if it keeps people with AIDS healthy, and stops or slows disease progression in those with HIV? Its quite a lot, apparently, as we look at the numbers of people who dont have access to the new therapies because of lack of insurance, under-funded AIDS drug assistance programs, lack of access to health care, and myriad other reasons. "The reality is that right now in America there are people living with HIV who do not have access to the drugs that can save their lives," Kawata said. "I think we have a responsibility to make sure that the drugs get to people that are sick." And for anyone undergoing PEP, insurance is most likely a moot point - few insurance companies will pay for a treatment regimen with drugs not approved for that purpose, particularly a treatment regimen where no hard proof of effectiveness or official standards of care exists. Which means that the treatment most likely will be paid for entirely by the patient. This has led to some concern that PEP will be an intervention that only serves the most privileged, those with the financial ability to "pay their way out" of an infection. In remarks at the CDC consultants meeting, NASTAD Chair Randall Pope of Michigan, said that this "may eliminate those most in need due to their poor socio-economic status." But on the other hand, given the limited prevention resources available, should this be considered a viable intervention in the context of current prevention programs? This is another reason that terminology plays such a role when discussing the implications of PEP. Post-exposure "therapy" or "prophylaxis" suggests a medical intervention that perhaps should be in the realm of treatment services covered by Medicaid, ADAP or other such programs. Post-exposure "management" or "prevention" suggests, perhaps, a combined focus on behavior and treatment that falls more appropriately under our traditional understanding of prevention interventions, such as prevention case management. These questions, of course, may be somewhat premature. With no guidelines on the treatment and no studies proving its success, there most likely will be no big push for broad implementation of PEP using prevention, care or treatment funding streams. But as the excitement about effective new treatments continues unabated, one cant underestimate the impact that both treatment therapies and PEP may have on the communities most at risk for HIV infection. Im very concerned that we have the potential to send out mixed messages about prevention of HIV in America," said Kawata. "I want people to remember that they have to use a condom and that they cant share needles. Any message that dilutes those challenges could really further the spread of HIV." Providing our target audiences, those at most risk for HIV infection, with accurate information and effective strategies is perhaps one of our most important challenges. At this time, we have a delicate balancing act to maintain - researching the effectiveness of a promising intervention that can prevent infections before they take hold, while maintaining the understanding that although medical science has made great strides, our basic approach should remain the same. The first line of prevention remains changing behavior, and maintaining that change over time. |
LETTERS From CAMP Rehoboth, Vol. 8, No. 10, July 31, 1998. |