CDC takes a large tiger by the tail: How to handle post-exposure treatment
Controversy, lack of data make guidelines hard to write
After more than 100 consultants met for two days in Atlanta to discuss the pros and cons of recommending post-exposure prophylaxis for sexual exposures to HIV, the Centers for Disease Control and Prevention remains months away from issuing a statement or possible guidelines on the controversial subject.
However, despite little efficacy data and a host of ethical dilemmas, clinicians are already prescribing combinations of drugs for exposed patients who are willing to bear adverse reactions and risk unknown long-term side effects.
"Adopting guidelines in the absence of data and there are precious few data about this subject is risky," said Keven deCock, MD, MPH, director of the CDC’s division of HIV/AIDS prevention, surveillance and epidemiology. "But we feel guidelines should be developed since post-exposure therapy is already being used in some quarters, and a statement defining best practices is required to avoid some of the potential negative consequences that might accompany widespread use or unthoughtful use of this intervention."
Toward that end, the CDC invited behavioral and medical researchers in late July to share insights on the emerging issue of post-exposure prophylaxis (PEP) using one or more drugs to reduce the chances of HIV infection after a person has been exposed to the virus for those who have experienced an unanticipated sexual or drug injection-related exposure to HIV. For more than 10 years, PEP has been offered to health care workers occupationally exposed to the virus. The CDC began recommending PEP last year after a case-control study in December 1995 unexpectedly found for the first time that PEP with zidovudine reduced the rate of infection in exposed health care workers by 79%.1,2 Since 1995, the CDC also has recommended PEP for reducing perinatal transmission.
The medical community has asked whether PEP should be offered for non-occupational exposures, such as rape victims, high-risk couples that experience condom breakage, and injection drug users who inadvertently share dirty needles.
Last July, the question grew more widespread when it was reported at the XI International Conference on AIDS in Vancouver that hospitals in British Columbia had begun offering post-exposure therapy to people with sexual exposures to HIV, including rape victims. (See article on the program on p. 101.)
"Since that time we have had numerous inquiries at CDC from a variety of different areas, particularly emergency room physicians, asking for guidance regarding post-exposure therapy for non-occupational exposures," said Robert Janssen, MD, a CDC epidemiologist who led the meeting. "We have heard that some physicians have already started to prescribe this therapy, and some apparently on a regular basis. However, in the absence of information on whether post-exposure therapy prevents infection in non-occupational exposures to HIV, it isn’t clear when or if post-exposure therapy should be used."
The two-day meeting raised more questions than it answered, and the input from experts seemed to weigh on the side of caution. Indeed, the CDC, in setting parameters for the meeting, was willing to consider PEP for single or isolated exposures only and for exposures involving nonconsensual sex, breast feeding, and injection drug use. Receptive anal intercourse was not considered. Nor did the group discuss what drugs would be most appropriate for PEP.
"We feel post-exposure therapy may be appropriate only for single or isolated exposures, although a definition of isolated exposure is open to discussion," Janssen explained. "We are not talking about pre-exposure therapy or continuous therapy. We are not talking about people being on these drugs for six months or a year at a time."
In his introductory remarks, Janssen noted that:
• PEP is likely to be less than 100% effective.
• The drugs used have side effects, some serious.
• PEP could increase the risk of producing resistant strains of HIV.
Because of these difficult scientific and social issues raised by non-occupational PEP, the CDC will convene a second working group later this year, Janssen said. If recommendations for PEP are made, they will be sent out for public comment and published in the Morbidity and Mortality Weekly Report early next year, he added.
CDC officials were reluctant to predict at this point what the recommendations might look like whether definitive and detailed, like those for occupational exposure, or just general statements about scientific rationales for using PEP. "It just might be putting down what we know and what we don’t know," Ron Valdeseri, MD, deputy director of the CDC’s Center for HIV/AIDS, STDs, and TB Prevention, tells AIDS Alert.
Kenneth Mayer, MD, director of the Brown University AIDS program and a presenter at the meeting, applauded the CDC for tackling such a controversial subject. He predicted the CDC would charge researchers to increase study in this area and offer broad guidelines. "I think there are going to be parameters for clinicians to consider PEP, and the CDC may consider some practices. But I don’t think there is enough clarity to come up with something really tight. It probably will have more fudge language than the occupational exposure guidelines."
After the two-day meeting, however, some participants doubted whether the CDC would make recommendations for PEP in non-occupational exposures. "I don’t think there are going to be any," said Alistair McLeod, MD, chief of the committee on accidental exposures for the Center for Excellence in HIV/AIDS in Vancouver, BC. "With the exception of a few of us, they seemed to think that they [CDC officials] had not made a case. Most people felt there wasn’t a whole lot of place for this prophylaxis."
The fact that the meeting was held at all generated strong criticism from AIDS activists, most notably ACT-UP San Francisco, which distributed a protest letter and issued derogatory chants denouncing PEP as a government promotion backed by pharmaceutical companies. The group’s biggest concern was public misconception about PEP and its use of AZT, which it claims is the most toxic drug approved by the federal Food and Drug Administration.
"This is neither prophylaxis nor is it post-exposure," said Mike Funk, a spokesman for the group. "We feel that labeling these morning-after clinics’ will give the public the wrong perception that they will be able to engage in unsafe sex and then to go a morning-after clinic, pop some pills, and then everything will be OK."
The group also fears that PEP might siphon off existing resources for AIDS treatment. "In rural America there already is a waiting list for HIV-positive people for protease inhibitors," Funk said. "How can you even open that market to include everybody without it coming to people who are already infected? We will not be put aside for intentionally infected people."
Will PEP erode prevention efforts?
The CDC warns that PEP, while offering a potential new tool in preventing new HIV infection, will have a "modest, if not small" impact on the epidemic in the United States. Too few people know the status of their partners or could receive PEP within the short window period of opportunity, which has been estimated to be within 72 hours of exposure. Yet health officials are concerned that the public perceives PEP as a "morning after pill," and that this misleading assumption could erode prevention efforts established over the past 15 years.
Indeed, the very need for PEP indicates a failure in prevention.
"The possibility of post-exposure therapy preventing some individuals from acquiring HIV infection is exciting, but it in no way changes CDC recommendations for setting the primary prevention of HIV infection," deCock said. "It is imperative that primary prevention not be weakened."
While many HIV behavioral scientists are concerned that the widespread availability of PEP would lead to increased risky behavior, others suggest that the harsh reality of PEP might burst illusions about HIV, said Susan Buchbinder, MD, chief of the research branch of the San Francisco AIDS Office. "There are reports of individuals who have taken PEP and said, Oh, this is what you meant by a chronic treatable disease. I didn’t realize the enormity of what it meant to be HIV-infected and this has brought it home.’"
Public health vs. individual control
What situations would be appropriate for PEP, and where to draw the line among different risk groups, raises a host of ethical issues, said Bernard Lo, PhD, a medical ethicist at the University of California at San Francisco. For instance, should a college student who has unsafe sex be denied PEP even though she is unwilling to accept what others would consider a low-risk event? How does that scenario compare to a prostitute who has repeated episodes of unprotected vaginal intercourse?
"One of the hardest things about this whole discussion is all the unknowns about what are the benefits of PEP and what are the risks," he said.
However, the CDC already has provided guidelines for occupational exposure. By most estimates, sexual exposures are equal to needlestick injuries in risk of HIV transmission, if not greater, he added. (See article on risk evaluation on p. 102.) If PEP is to become a significant prevention tool, it would have to be expanded beyond health care workers, as occupationally transmitted HIV makes up less than 1% of HIV cases in the United States, he noted.
Nonetheless, PEP for occupational exposure has important ethical and clinical differences from PEP for sexual or injection drug use exposures that set it apart, Lo said. They include:
• Researchers have years of data on the risk of transmission from needlestick and sharps injuries. The data have been gathered in a systematic way, unlike data for other exposures.
• Because most occupational exposures occur in the health care setting, the HIV status of the index patient is usually known. The serostatus of contacts from sexual or drug exposures is often not known, which could lead to unnecessary treatment of healthy people.
• Most occupational exposures are single exposures. Sexual and drug exposures can be the result of repeated encounters.
• The health care setting provides an infrastructure that warrants easy access to treatment and advice.
• The risk of occupational exposure is unavoidable for health care workers. PEP can reduce that risk and make the profession more attractive. The same kind of social benefit cannot be found from sexual or drug exposures.
Complicating the issue is the fact that many of those who are likely to benefit most from PEP, such as gay men who have unprotected receptive anal intercourse, are often involved in other behaviors that would make them less likely to complete therapy, said Seth Kalichman, a researcher for the Share Project at Georgia State University in Atlanta. "Our data are clear that people most likely to be interested in PEP are the best candidates in terms of risk," he said. "However, in terms of adherence, they are the most likely to use drugs and be younger, so these behavioral considerations have to be included in any kind of recommendation."
References
1. Centers for Disease Control and Prevention. Update: Provisional public health service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR 1996; 45:468-472.
2. Centers for Disease Control and Prevention. Case-control study of HIV seroconversion in health-care workers after percutaneous exposure to HIV-infected blood France, United Kingdom, and United States, January 1988-August 1994. MMWR 1995; 44:929-933.
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