Updated postexposure guidelines stress need for expert advice
Updated postexposure guidelines stress need for expert advice
Updated science, drug toxicity info help clarify treatment issues
The Centers for Disease Control and Prevention has updated its guidelines for postexposure HIV prophylaxis for health care workers, providing more refined criteria for establishing risk and choosing from a growing number of treatment options.1
"We have tried to streamline the recommendations and provide some guidance on decision making from the moment of exposures," says Linda Chiarello, MS, medical epidemiologist in the CDC's hospital infections program.
Hindered by limited data on the efficacy of postexposure prophylaxis (PEP) in humans, the CDC had not recommended preventive therapy for exposed health care workers until two years ago, following the results of a large case-control study evaluating PEP in workers in the United States and Europe. The findings, while controversial, showed that the risk of HIV infection among health care workers who used AZT for PEP was decreased by 81%. AZT preventive therapy also has been shown to reduce mother-to-child HIV transmission by 67%. Nonetheless, AZT monotherapy regimens of PEP had been documented as failing at least 14 times, the CDC notes. Delayed treatment, exposure to high-titer inoculum, and exposure to an AZT-resistant strain are possible explanations for the failure.
A total of 52 health care workers in the United States have been documented with occupational HIV infection as of June 1997. Another 114 infected workers are considered possible occupational exposure cases because they had no risk factors for infection, even though transmission from a specific exposure was not documented. The CDC reports that 47 of the 52 workers were exposed to HIV-infected blood, one to body fluid, one to an unspecified fluid, and three to concentrated laboratory virus.
The CDC also reports unpublished data showing that 81% of documented occupationally infected health care workers experienced symptoms compatible with primary infection a median of 25 days after exposure. The median time from exposure to seroconversion was 46 days, which is a similar time course for nonoccupational modes of transmission, the agency reports. (See story on p. 75 for more information from the CDC's PEP registry.)
While the new guidelines for managing PEP cases are fairly clear-cut and similar to the previous 1996 guidelines, choosing the right regimen has become more complex in recent years. The recommendations for PEP have been modified from the previous guidelines into two protocols:
· A basic four-week regimen consisting of two drugs [zidovudine (AZT) and lamivudine (3TC)] is recommended for most common HIV exposures.
· An expanded regimen using the addition of a protease inhibitor (indinavir or nelfinavir) is recommended for exposures with an increased risk of transmission or where there is exposure to known or suspected resistant strains of HIV.
The CDC notes that the potentially toxic nature of combination therapy makes treatment for negligible exposures unjustified, and that a highly active regimen is not recommended for all HIV exposures. Indeed, the "basic" two-drug regimen should be appropriate for most HIV exposures, while the "expanded" three-drug regimen is reserved for high-risk exposures or where resistance to one or more drugs is known or suspected. Both regimens are four weeks long.
Don't hesitate to consult with experts
Because prompt reporting and treatment is vital and patient management has grown more complicated with the availability of more drugs, the CDC document strongly urges that facilities have systems in place for timely evaluation and management. It also recommends consultation with experts in HIV treatment when initiating PEP.
"One of the important messages is that we are encouraging consultation with experts in infectious disease and in care of persons with HIV," Chiarello says. "We know these drugs are not benign, protease inhibitors have many interactions with other drugs, and there are professionals out there in an ideal position to guide in the decision-making process."
Another message stressed in the guidelines is the need for institutions, particularly those that may not have expertise in PEP, to link up with organizations that have experience with the drug regimens and management of HIV cases. Home care and long-term care facilities are examples of providers that could benefit from community linkages, she adds. (See list of resources, above right.)
Two areas given more attention in the new guidelines are the decision to treat exposures in pregnant women, and addressing the issue of exposure to known or suspected resistant strains.
The main consideration in treatment of pregnant women is the side effects of drugs that have not been extensively evaluated in pregnant women. Pharmacokinetic data on AZT show no increased risk for birth defects. Data are limited on 3TC alone or in combination with AZT in HIV-positive pregnant women; however, the drug appears safe during pregnancy for women and infants, the CDC notes.
There are no safety and tolerability data for protease inhibitors in pregnant women. One concern is that the hyperglycemia seen in HIV-infected people could exacerbate the risk of pregnancy-associated hyperglycemia, the guidelines state.
The significance of exposure to drug-resistant strains of HIV is not well-understood. Transmis sions of resistant strains have been reported, yet AZT was shown to prevent perinatal transmission of virus that was genotypically resistant to AZT.
Now that PEP will be given in combinations of two or more drugs, the odds of treatment not being susceptible to the virus are less than when monotherapy was recommended, experts note. At the same time, however, with more HIV-positive patients on combination therapy, the pool of drug-resistant strains is increasing. Consequently, the guidelines provide flexibility in this area, deferring to local knowledge and judgment about local resistance patterns and patient characteristics, Chiarello says.
Rapid tests recommended
"There are real concerns about resistance," she says, particularly with significant exposures involving patients who have lots of drug experience. "And this is where consultation and local knowledge of resistance patterns and antiretroviral drug use in the community is important."
Another addition to the new guidelines is the recommendation to consider using an FDA-approved rapid HIV-antibody test. With one rapid HIV test approved and several others expected to be put before the FDA for approval this year, more rapid HIV testing is being used for occupational exposure because testing by enzyme immunoassay cannot be completed within one to two days. While the CDC recommends that treatment begin as soon after the exposure as possible, a rapid HIV test can shorten the period for which an exposed worker must be treated if the source proves to be HIV-negative, Chiarello says.
Data collected from the CDC's PEP registry, which was started in October 1996, show that 39% of workers who stopped PEP did so because the source patient turned out to be uninfected, she adds.
Reference
1. Centers for Disease Control and Prevention. Public health service guidelines for the management of health care workers exposed to HIV and recommendations for post-exposure prophylaxis. MMWR 1998; 47/No. RR-7.
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