Registry finds 3 drugs most favored PEP regimen
So far, no unusual side effects in health care workers
Analysis of nearly 300 health care workers who have been treated with HIV postexposure prophylaxis (PEP) and reported to the Center for Disease Control and Prevention's PEP registry shows that more than half are starting off with three drugs and about 20% stop treatment prematurely because of intolerance.
"The impression I am getting from the registry is that a number of infection control practitioners have decided to start with three drugs automatically rather than doing a lot of interpretation over whether they should take two or three," says Susan Wang, MD, medical epidemiologist at the CDC's hospital infections branch. "About 65% or more are taking three drugs."
`We have to be cautious about being too rigid'
The fact that most health care workers are receiving three drugs initially instead of two raises the question of whether clinicians are being overaggressive. Lacking detailed information on the severity of exposures, CDC officials are hesitant to question clinicians' judgment, says Linda Chiarello, MS, a CDC medical epidemiologist who co-wrote the CDC's new guidelines on PEP.
"It is hard to assess whether people are being inappropriately treated, " she says. "We have to be cautious about being too rigid. We have made a compelling argument for a two-drug regimen, but there are those who disagree and think it is better to use more than two drugs. If there is a true exposure that could lead to transmission, it is better to give people at least three drugs, and some people are giving four."
To date, the registry, which was set up in October 1996, has received reports of PEP from 295 health care workers. Follow-up data are available for 219 cases. Of that group, 89 have stopped treatment prior to the recommended four weeks. About half (44) discontinued because the source patient turned out to be HIV-negative. The other half stopped because of intolerance, Wang adds.
The registry also reveals that all types of combinations of drugs are being prescribed for PEP, but the most common regimen is zidovudine (AZT) and lamivudine (3TC). That has been made more attractive with recent approval of combivir, a single tablet containing both AZT and 3TC. The most commonly prescribed protease inhibitors are saquinavir and indinavir, although that may change since nelfinavir became approved last year, she adds.
Although the registry doesn't have detailed information on the severity of exposures, more than 85% were percutaneous injuries. The registry doesn't have information on the occupations of those who are treated. Two studies are following PEP at specific hospitals and are gathering that type of information, Wang notes.
Side effects not unusual
The main reason for setting up the registry was to gather data on how health care workers respond to combinations of antiretroviral drugs. Until the PEP registry was created, health officials had little, if any, information on how healthy individuals react to two or more drugs.
"Side effects are increased when someone is put on three drugs, but they are not totally intolerable," says Chiarello.
So far, the types of side effects noted in health care workers are those reported in infected patients, Wang says. Approximately three out of four workers on PEP have experienced some degree of side effects, the preponderance being fairly mild, such as nausea, occasional diarrhea, headaches, and fatigue. Some patients on indinavir have reported kidney stones, she adds.
The CDC has no way of knowing how many health care workers are put on PEP each year. Facilities were slow in reporting PEP cases at first, but now the registry is averaging about 40 cases reported a month. Until the registry has a larger sample size, the CDC is reluctant to make definitive observations about which combination might be most tolerable, says Wang. Some comparative data will be out in the next year, she adds.
"As we get bigger numbers, if we find any unique or bizarre symptoms, we would step back and say something about that combination," she tells AIDS Alert. "But so far we haven't seen anything other than what the drug companies are reporting."
In addition to obtaining information on side effects, the registry is tracking when side effects first show up. What CDC officials have seen so far is that most symptoms start appearing within three to four days after the regimen has been started. Having that information is helpful in counseling workers because it helps them anticipate the experience and prepare for it, Wang notes. The new CDC guidelines for PEP for health care workers recommend that workers be offered medication to counteract symptoms that get out of hand, such as antiemetic or antidiarrheal drugs.1
"We want to get them through the bad symptoms so they can continue to take the regimen," Wang says.
Timely treatment emphasized
The guidelines underscore the importance of offering PEP as soon after the exposure as possible, and the CDC is interested in finding out how soon treatment is offered. The reports from the registry indicate that workers are receiving treatment in a timely fashion - an average of 1.75 hours after exposures. Although a few workers have had treatment deferred up for a day or more (the longest recorded delay was 10 days), most are receiving drug within two to three hours, Wang adds.
Animal studies indicate that PEP may not be effective if initiated later than 24 to 36 hours after exposure. However, because the effect on humans is unknown and because early treatment of acute HIV infection is beneficial if infection is not prevented, the CDC recommends initiating therapy even after one to two weeks for high-risk exposures.
As for drug efficacy, the CDC has no basis for comparison because so far there have been no reports to the registry of a health care worker who received PEP and seroconverted.
[Editor's note: Health care providers are asked to enroll all health care workers who receive PEP in a confidential registry that was developed through the cooperation of the CDC, Glaxo Wellcome Inc., and Merck & Co. The registry's telephone number is (888) 737-4448. Providers also should report instances of prenatal exposure to antiretroviral agents to the Antiretroviral Pregnancy Registry at (800) 258-4263.]
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.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content