Most unknown source exposures don’t need PEP

New guidelines clarify, minimize use of PEP

In an effort to reduce the unnecessary use of HIV post-exposure prophylaxis (PEP), the Centers for Disease Control and Prevention in Atlanta issued guidelines that raise the threshold for PEP when the HIV status of the source patient is unknown.1 While clinicians once may have issued PEP as a safeguard whenever the source patient or the source patient’s HIV status was unknown, significant side effects to some PEP agents have led CDC to urge a more cautious approach.

"We have noticed from our data analysis that it’s not uncommon for people to take full courses of PEP after unknown [source patient] exposures," says Elise Beltrami, MD, medical epidemiologist in CDC’s division of healthcare quality promotion. "We’re really trying to emphasize the need to evaluate these situations using information you might have about the source patient or the situation epidemiologically in which the incident took place."

For example, consider a needlestick that occurs from a needle left in linens. If HIV is not prevalent in the community or the patient population and the unit isn’t treating any patients with known HIV or HIV risk factors, the risk is minimal, says Beltrami. "The point is in unknown situations, the majority of the time the source patient is going to be HIV-negative," she says.

However, the CDC leaves plenty of room for clinical judgment. The Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis is a user-friendly document that includes the three major bloodborne pathogens and offers algorithms and resource charts. While just a few PEP agents were recommended for use when provisional guidelines were first released in 1996, a table now offers the pros and cons of 13 PEP agents and regimens. (To see recommendation tables, click here.)

CDC’s advice to seek expert opinions is right on the mark, particularly as clinicians try to determine the most appropriate PEP agents, says Mark Russi, MD, MPH, associate professor of medicine, epidemiology, and public health at Yale University in New Haven, CT, and director of occupational health at the Yale-New Haven Hospital. Russi also lauded the ease of use of the guidelines. "We give prophylaxis to an awful lot of people, but I have a network of infectious disease specialists that I speak to all the time about this," he says. "I’m not out there treating HIV-positive patients every day. I find there’s tremendous benefit in speaking to specialists."

The possible risks of PEP were highlighted earlier this year when the CDC and the Food and Drug Administration issued a joint report urging clinicians to balance the risks of HIV infection with the toxicity of the PEP agents.2 Reports of severe side effects to nevirapine include the case of a 43-year-old phlebotomist who developed severe hepatic failure, lapsed into a coma, and required a liver transplant.3 (See Hospital Employee Health, February 2001, p. 22, and HEH, March 2001, p. 34.)

"One of the first goals of any clinical management is to first do no harm," explains David Bangsberg, MD, MPH, director of the Epidemiology and Prevention Interventions Center at San Francisco General Hospital and co-director of PEPline, a 24-hour post-exposure hotline. "Post-exposure prophylaxis can cause serious toxicity, even fatal toxicity. Most people will remain uninfected without any post-exposure prophylaxis. The goal is to target post-exposure prophylaxis to those who need it most."

PEPline experts can help assess the risk and the need for PEP, Bangsberg notes. A review of 4,253 consultations in the hotline’s first year found that 58% resulted in a recommendation to stop or not start PEP. Seven percent of callers reported having initiated or receiving two- or three-drug regimens after an event that was not a true exposure.4

While CDC wants to reduce the unnecessary use of PEP, the guidelines also address the problem of health care workers who halt the regimen because of side effects. Data from the National Surveillance System for Healthcare Workers (NaSH) showed that 63% percent of health care workers exposed to a known HIV-positive source started PEP, and 54% of health care workers took it for at least 20 days. The NaSH data from 47 U.S. hospitals involves 11,784 exposures from June 1996 to November 2000.4

For all exposures with known sources, 6% were to HIV-positive sources, 74% to HIV-negative sources, and 20% to sources with an unknown HIV status, according to the NaSH data.

CDC recommends a re-evaluation of PEP after 72 hours, a follow-up that may lead to the discontinuation of unnecessary regimens or a treatment of side effects for those who need the PEP. "We’re hoping there are more people completing the regimens they should be taking," says Beltrami.

The CDC also clarified its advice about the timing of PEP. While studies show that starting PEP within an hour or two of the exposure is advantageous, a delay doesn’t mean that PEP is useless. The guidelines state that PEP should be started even 36 hours or more after exposure, if appropriate. "Initiating therapy after a longer interval [such as one week] might be considered for exposures that represent an increased risk for transmission," the guidelines state. "The optimal duration of PEP is unknown. Because four weeks of zidovudine appeared protective in occupational and animal studies, PEP probably should be administered for four weeks, if tolerated."

Since many source patients are already on anti-retroviral therapy, the choice of PEP agents can become complicated, and expert opinion is recommended. "The prevalence of HIV drug resistance is on the rise, which makes it more complicated to pick a PEP regimen which will likely be effective against a potentially resistant strain of HIV in the source patient," Bangsberg says.

The guidelines also respond to another difficult and controversial question: Can anything be done to help occupationally exposed health care workers avoid chronic HCV infection? CDC reiterated its position that no evidence exists showing that antiviral agents such as interferon would be effective as a prophylaxis in preventing HCV infection.

While HCV RNA tests can identify infection at four to six weeks, the use of antivirals at this early stage is not necessarily advantageous, the guidelines state. As many as one in four patients may resolve their HCV infection spontaneously, and providing treatment with interferon and ribavirin may be just as effective in the early chronic stage of HCV, according to the guidelines.

"It’s frustrating not to have anything to offer health care workers after an exposure, but certainly we don’t want to do any harm [with unnecessary side effects] in this situation," Beltrami says.

Again, clinicians will evaluate their specific circumstances. "Based on a very small amount of data, and in consultation with a hepatologist, it might be reasonable to put someone with acute hepatitis C infection on interferon and ribavirin," says Russi, although he adds, "We don’t know if that’s better than waiting. There really isn’t adequate evidence at this point to say that treating that person who seroconverts at four to six weeks is absolutely advantageous over treating them at an early chronic stage."

[Editor’s note: The guidelines are available on CDC’s web site at www.cdc.gov/mmwr/preview/mmwrhtml/rr5011a1.htm. Post-exposure advice is available from the National Clinicians’ Post-Exposure Prophylaxis Hotline (PEPline) at (888) 448-4911.]

References

1. Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR 2001; 50(RR11):1-42.

2. Centers for Disease Control and Prevention and Food and Drug Administration. Serious adverse events attributed to nevirapine regiments for postexposure prophylaxis after HIV exposures — Worldwide, 1997-2000. MMWR 2001; 49:1,153-1,156.

3. Johnson S, Baraboutis J, Sha BE, et al. Adverse effects associated with use of nevirapine in HIV postexposure prophylaxis for 2 health care workers. JAMA 2000; 284(21): 2,722-2,723.

4. Bangsberg D, Goldschmidt RH. Postexposure Prophylaxis for Occupational Exposure to HIV (letter). JAMA 1999; 282:1,623-1,624.