Jury still out on HIV postexposure prophylaxis despite more evidence
Decision on correct drug therapy regimen remains a difficult one
Despite new recommendations for postexposure prophylaxis (PEP) from the Centers for Disease Control and Prevention, questions remain concerning the efficacy and toxicity of the drugs prescribed for health care workers who suffer occupational HIV exposures. The choice of two-drug vs. three-drug therapy remains a significant dilemma, as well.
Occupational medicine professionals often are caught in a bind over such issues, says renowned health care worker exposure expert David K. Henderson, MD, deputy director for clinical care at the National Institutes of Health (NIH) in Bethesda.
Henderson, who addresses the issue of HIV PEP at health care conferences around the country, continually faces this question: Would he take prophylactic drug treatment himself should he be confronted with the need to make that decision? He always refuses to answer.
"It’s the most common question I’m asked, but I won’t answer it," Henderson tells Hospital Employee Health. "The reason is not because I don’t think I know what I would do intellectually, but because I really view this as a crisis when it happens in the life of a health care worker. In crisis situations, people don’t always behave the way they think they would. They often make different decisions. I try not to be presumptuous and answer that question simply because I’m not certain how I’d behave in that particular crisis."
PEP in the real world
Henderson’s response reflects his focus on the use of PEP "in the real world" instead of a purely intellectual approach to guidelines on paper. (For "real world" experiences, see related story, p. 76.) Years of experience with HCWs exposed to blood have taught him that "[each worker] thinks it’s the most severe exposure in the history of mankind," he says. That makes risk stratification leading to prophylactic drug treatment decisions — two drugs, three drugs, or no drugs — difficult to accomplish, no matter how clear and logical the current guidelines are.
An HCW to whom two drugs are offered may know that a co-worker exposed last week is taking three drugs, Henderson says, and could object to being offered only two.
While risk stratification appears to be practical from an implementation standpoint, "when a[n exposed] health care worker is looking you in the face, it’s much harder to try to convince that person that two drugs is probably adequate in their situation," Henderson remarks. "We often end up giving three drugs."
Another problem in assessing exposure risk arises when the source patient’s HIV status is unknown, Henderson adds.
Given those difficulties, why not offer all three drugs every time and avoid the risk stratification process completely?
The updated CDC guidelines released last year include algorithms based on exposure type and source patient HIV status to help clinicians and exposed workers decide whether PEP is warranted, and if so, whether the basic two-drug regimen or the expanded three-drug treatment should be used.1
Third drug is protease inhibitor
The two-drug regimen consists of zidovudine and lamivudine, while the expanded regimen for exposures that pose an increased HIV transmission risk adds a protease inhibitor, such as indinavir or nelfinavir.
The 1998 guidelines updated the 1996 version,2 taking into account several new antiretroviral drugs and additional data about the use of antire troviral agents in exposed HCWs. (See Hospital Employee Health, July 1998, pp. 81-86.)
Of the three drugs included in the CDC’s PEP guidelines, only zidovudine has shown any prophylactic efficacy.3 In a recent article reviewing the history of HIV PEP, mechanisms of action, safety, efficacy, and clinical management, Henderson notes that data support but do not prove the efficacy of antiretrovirals used to prevent HIV transmission following occupational exposure.4 Thus, he says he stops short of "recommending" PEP for exposed workers.
"It’s a fine point, but in general I make recommendations for therapy when we know definitively that a drug works. We do not know definitively that these drugs work in this setting," he states. "We may have been the first to offer these drugs, and we continue to offer them but not recommend them."
Henderson says he tries to help HCWs make informed decisions, providing "every piece of information I can lay my hands on" regarding toxicity, efficacy, risk, and other factors. Because timing is important, he often offers the first dose right away while workers are still deciding.
An open-label postexposure prophylaxis safety trial has been under way for the past six years at the NIH and 17 other sites around the country, in which Henderson and colleagues are giving three-drug therapy to all exposed workers who choose to participate. The study is an attempt to quantify subjective toxicities HCWs sustain from the drugs. Thus far, their data show that subjective toxicity is no greater for three drugs than for two or zidovudine alone, he says.5
Nevertheless, Henderson acknowledges that subjective toxic effects reported in studies of HCWs taking PEP treatment are "substantial."4
Similar concerns were discussed in another recent study from Boston Medical Center (BMC), where researchers evaluated the use of combination antiretroviral therapy for PEP in 68 workers over a 12-month period. Twenty-three took zidovudine and lamivudine, and 45 took those two drugs along with indinavir. Fifty-one of the 68 HCWs (75%) reported one or more side effects. Side effects were more common among those taking three drugs.6
The most commonly reported side effects were nausea (65%), malaise and fatigue (52%), and headache (23%). One physician developed nephrolithiasis attributed to indinavir, and another physician was hospitalized more than a week for fever, severe pancytopenia, and dehydration attributed to the three-drug regimen.
Indinavir causes problems
Lead researcher Robert B. Swotinsky, MD, MPH, who was director of the occupational health program at BMC during the study, says indinavir in the three-drug PEP treatments caused most of the problems. He subsequently tries to avoid prescribing it whenever possible.
"It’s encouraged me to provide two-drug therapy sometimes where three-drug therapy is the other option because I want the person to continue [therapy] for the full course, and I know the third drug is a killer,’" he states.
At first, Swotinsky was more amenable to offering three-drug prophylaxis. "We said, What could it hurt?’ But that wasn’t the case. Later on, we became more gun-shy about it."
In the study, several workers and students on PEP missed work and classes due to side effects, and some workers did not return to their jobs.
"Adherence to combination antiretroviral medication regimens is difficult," the study notes. Treating side effects such as nausea with antie me tics and headache with aspirin or other medications does not solve all workers’ problems, Swotinsky says.
"You can throw Compazine at them, but they still feel like the walking wounded and sometimes can’t function at work. That’s not going to fix the whole problem, because they’re going to continue to take the [PEP] medicines, and they really get wrapped up in other stressful issues, like the source patient refusing to get tested or not getting workers’ compensation benefits," he points out.
Prescribing and monitoring PEP are more complicated tasks than many others provided by employee health services, Swotinsky says. He recommends a coordinated approach involving infectious disease and AIDS specialists. Ade quate resources also are needed for effective counseling and follow-up of employees on PEP.
While BMC is part of a major academic medical center with a high prevalence of HIV-infected patients, Swotinsky surmises that implementation of PEP guidelines is challenging for other health care facilities as well.
In fact, BMC is part of the multifacility National Surveillance System for Hospital Health Care Workers (NaSH), an ongoing CDC study that, in part, evaluates participating hospitals’ experiences with PEP based on employee health service data.
Preliminary information from NaSH shows that only about 50% of exposed HCWs come back to the EHS for follow-up after initial counseling, says Adelisa L. Panlilio, MD, medical epidemiologist in the CDC’s hospital infections program. She suspects this may have something to do with lower rates of initially prescribed PEP therapy completion, shown to be about 46%, according to data from the now-closed HIV PEP Registry.7
Panlilio contrasts that finding with results of a San Francisco pilot program in which non-HCWs were prescribed PEP therapy for nonoccupational exposures and showed "amazing compliance" of about 75% with the entire prescribed regimen, she says.
"A lot has to do with counseling and motivation," Panlilio states. "In San Francisco, there was extensive counseling at first, patients were given one week of drugs, came back for more counseling, were given another week of drugs, came back again for counseling, then two more weeks of drugs, and back in for more counseling."
Such extensive counseling "doesn’t speak well for what’s going on with health care workers," she says, adding the CDC is "very interested" in trying to determine why exposed HCWs are not counseled more aggressively — whether they avoid coming in for some reason or whether counseling and follow-up programs need bolstering.
However, Panlilio notes that many employee health services in U.S. hospitals are "strapped" for resources.
"This is only one of numerous activities in which they’re involved. Many occupational health practitioners are part-time and may also be the hospital’s infection control practitioners," she says, "so they’re running in many different directions."
References
1. Centers for Disease Control and Prevention. Public Health Service guidelines for the management of health-care worker exposures to HIV and recommendations for postexposure prophylaxis. MMWR 1998; 47(No. RR-7):1-33.
2. Centers for Disease Control and Prevention. Update: Provisional Public Health Service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR 1996; 45:468-472.
3. 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.
4. Henderson DK. Postexposure chemoprophylaxis for occupational exposures to the human immunodeficiency virus. JAMA 1999; 281:931-936.
5. Gerberding JL, Fahrner R, Beekmann SE, et al. Combination post-exposure prophylaxis (PEP): A prospective study of HIV-exposed health care workers (HCW). In: Program and abstracts of the 12th International Conference on AIDS. Geneva; June 28-July 3, 1998.
6. Swotinsky RB, Steger KA, Sulis C, et al. Occupational exposure to HIV: Experience at a tertiary care center. J Occup Environ Med 1998; 40:1,102-1,109.
7. Wang SA, Panlilio AL, and the HIV PEP Registry Group, CDC, Atlanta. Experience of health-care workers (HCWs) taking postexposure prophylaxis (PEP) after occupational human immunodeficiency virus (HIV) exposures: Findings of the HIV PEP Registry. Presented at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego; Sept. 24-27, 1998.
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