Important note: Information in this article was accurate in 2003. The state of the art may have changed since the publication date. An inmate reports being raped (anally penetrated) by another inmate and is sent to a local emergency department (ED) within two hours after the assault. The assaulted inmate denies any past or current injection drug use (IDU) or sex with men (except the assault) and recently tested negative for HIV infection; the hepatitis B virus (HBV) and hepatitis C virus (HCV) serostatus is unknown. The assailant is a previous injection drug user. He is known to have chronic HBV and HCV infection, however his HIV status is unknown.
What should the emergency department physician initially do with the assaulted inmate?
The ED physician should first ensure that the assaulted inmate is medically stable. This includes ruling out ongoing bleeding or colonic perforation from the assault. Any mucosal or skin tears should be promptly irrigated in sterile fashion. A forensics examination kit can be used to collect specimens that may be required for legal evidence of the assault, but this should not delay decontamination procedures.
What type of testing should be done, and when?
Initial serology testing: Baseline serum testing of the assaulted inmate for antibodies to HIV and HCV is indicated, as well as a battery of HBV tests to establish his HBV status (immune, non-immune, or chronically infected). The HBV tests should include hepatitis B surface antibody (HBsAb), hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAb). These tests should be performed before HBV post-exposure prophylaxis (PEP) is administered.
Baseline labs: A baseline complete blood count (CBC), an electrolyte panel, and liver function tests should also be performed if the assaulted inmate is to begin antiretroviral prophylaxis against HIV.
Cultures: Rectal cultures should be obtained for gonorrhea and chlamydia. Testing of the source inmate or patient should be performed, if possible (consent may be required), and should include HIV antibody testing, a serum rapid plasma reagin (RPR) to screen for syphilis, and gonorrhea and chlamydia testing (by urine ligase chain reaction [LCR] testing). Any genital lesions present on the source patient should be cultured as well.
HIV: Follow-up HIV antibody testing for the assaulted inmate is indicated if the source patient is tested and found to be infected with HIV, or if the source patient cannot be tested for HIV. Some clinicians might argue in favor of performing this follow-up testing on the assaulted inmate even if the source patient tests negative for HIV at the time of the exposure, given the theoretical possibility that the source patient could be in the "window period" of acute HIV infection prior to antibody seroconversion.
HIV antibody testing performed at six weeks, three months, and six months is a reasonable schedule for follow-up testing and is recommended for occupational percutaneous exposures to HIV.1 Case reports of delayed HIV seroconversion in health care personnel who became coinfected with HIV and HCV from percutaneous exposures2,3 have prompted recommendations to consider HIV antibody testing at 12 months post-exposure in health care personnel who contract HCV from co-infected patients.4 If it is established that the source patient in this case is co-infected with HCV and HIV, and the assaulted inmate contracts HCV from the exposure, it would be reasonable to apply this reasoning to the present case, and perform HIV antibody testing at 12 months as well. HIV RNA polymerase chain reaction (PCR) testing ("viral load") would be indicated only if the source patient is found to be HIV-infected and the assaulted inmate develops signs and symptoms consistent with acute HIV infection.
If the assaulted inmate initiates antiretroviral PEP for HIV, as recommended below, then follow-up CBC, electrolyte panel, and liver function tests should be performed two weeks later to monitor potential medication-related toxicities.
Hepatitis B: If baseline HBV serologies suggest that the assaulted inmate is 1) currently not infected with hepatitis B; and 2) not immune to hepatitis B infection, then follow-up testing for hepatitis B seroconversion is indicated. Specific guidelines for this scenario are lacking, but a reasonable approach would be to test for HBsAg periodically. A recommended schedule is six weeks, twelve weeks, and six months, the same schedule that would be followed for HIV antibody testing, and as suggested by any clinical signs/symptoms of acute hepatitis.
Hepatitis C: Follow-up testing will be required for HCV, though sexual exposure does not appear to be an efficient mechanism for transmitting HCV. The Centers for Disease Control and Prevention (CDC) recommends testing for hepatitis C antibody four to six months following percutaneous occupational exposure, and this would be a reasonable standard to use in this case. Simultaneous alanine aminotransferase (ALT) testing can be performed, though this is a less reliable marker of HCV infection. If hepatitis C antibody seroconversion occurs, referral for further testing and medical management is indicated, which would include a HCV viral load for confirmatory testing and a discussion of treatment options if the inmate develops chronic hepatitis C infection.
Would you recommend PEP? Why or why not?
I would recommend PEP for HIV and HBV in this situation. Empiric treatment of possible gonorrhea and chlamydia infection should also be considered.
I would consider the source patient (the assailant) to be at high risk for HIV infection given he is known to be infected with both HBV and HCV, both of which share similar routes of transmission as HIV (sex and IDU). For the assaulted inmate, this type of exposure itself is very high risk: a single act of unprotected receptive anal intercourse involving an HIV-infected source patient carries a risk estimated at 1-2% for HIV transmission.5 Furthermore, this case involved rape, and the violence associated with acts of rape often results in tearing of the rectal mucosa, which could be expected to further elevate the risk of HIV transmission.
I would recommend an expanded three-drug PEP regimen such as zidovudine + lamivudine + nelfinavir (AZT + 3TC + NFV). I suggest the nucleoside backbone of AZT + 3TC because AZT has demonstrated efficacy for PEP in the setting of health care workers who have sustained percutaneous needlestick injuries.6 As we have no conclusive evidence regarding the efficacy of PEP for sexual exposures in humans, we can only extrapolate from what is known about PEP for occupational exposures. We add 3TC because PEP regimens generally include at least two drugs and because 3TC is generally very well tolerated. The addition of a third drug in this case, such as NFV, is a bit more controversial. We actually have no evidence that adding a third drug to a standard two-drug PEP regimen offers any added protection against HIV infection, even in the setting of an occupational percutaneous exposure; furthermore, adding a third agent generally adds more potential for antiretroviral medication-related toxicities.7
On the other hand, drawing from our experience in treating chronic HIV infection, we recognize that three agents may be more effective than two in suppressing HIV infection, and NFV is a relatively benign protease inhibitor whose main side effect - diarrhea - can generally be controlled with anti-diarrheal agents. Hence, I would recommend a three-drug PEP regimen, while recognizing the relative paucity of evidence to support this recommendation. Should the patient experience intolerable side effects from the NFV, discontinue this agent, and substitute either a different third agent, for example indinavir (IDV), or simply continue the basic AZT/3TC regimen without a third agent.
Ideally, the source patient would be tested for HIV infection. Should he test negative, PEP for the assaulted inmate should be discontinued. If the source patient tests positive, however, PEP should be continued for a total of 28 days, followed by periodic HIV antibody testing as outlined above.
Because the source patient is known to have chronic hepatitis B infection, this exposure places the assaulted inmate at risk of contracting hepatitis B, unless he is already immune. However, we currently have no evidence that he is immune to hepatitis B. I would therefore recommend HBV PEP, including 1) hepatitis B immune globulin (HBIG); and 2) initiation of the HBV vaccination series. Each should be given as soon as possible (though after baseline hepatitis B serologies are drawn, as outlined above). These two injections can be administered simultaneously but they should be administered at different sites on the body. It is believed, based on evidence from postpartum neonatal prophylaxis studies to prevent vertical transmission8,9 that the addition of HBV vaccination to the use of HBIG following potential exposure to HBV further reduces the risk of HBV infection. This is the same management that would be indicated for an unvaccinated health care worker who has sustained a percutaneous occupational exposure to a patient with chronic HBV infection.10 If baseline hepatitis B serologies indicate that the assaulted inmate is not immune to hepatitis B infection, the vaccination series should be continued. Six to eight weeks after the last injection of this three-shot vaccination series, a surface antibody titer can be checked to see if the vaccine elicited a protective antibody response.
There is currently no recommended post-exposure prophylaxis to prevent HCV infection. Recent data suggest that early treatment (within four months) of acute hepatitis C infection with interferon may substantially increase the likelihood of successful eradication over that historically seen with treatment of chronic hepatitis C infection.11 For this reason, some clinicians might favor screening the exposed patient with HCV RNA PCR (viral load) tests periodically, e.g. on a monthly basis, and initiating interferon therapy if HCV viremia is detected. However, given the potential toxicity of interferon, the fact that a significant minority of patients spontaneously clear HCV viremia without therapy, and the possibility that waiting for six months may not jeopardize a favorable response to treatment, other clinicians might favor simply screening six months following the exposure. More evidence is needed before definitive recommendations can be made regarding early screening and treatment of acute hepatitis C infection.
It may be appropriate to offer treatment for gonorrhea and chlamydia to the assaulted inmate, especially if physical examination of the assailant suggests the presence of either of these sexually transmitted diseases. If, however, the source patient can be tested for these infections, it would also be reasonable to defer the treatment decision until the results of these tests are known, given that follow-up care of the assaulted inmate can be guaranteed in this setting.
As the above case illustrates, the management of exposures to infectious pathogens involving considerations of PEP can be complex. Clinicians are reminded of telephone consultation services such as the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline), available 24 hours a day/7 days a week, at 1-888-HIV-4911.
* Nothing to disclose.
**Speaker's Bureau, GlaxoSmithKline.
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(No. RR-11).
2. Ridzon R, Gallagher K, Ciesielski C, et al. Simultaneous transmission of human immunodeficiency virus and hepatitis C virus from a needle-stick injury. N Engl J Med. 1997 Mar 27;336(13):919-22.
3. Ciesielski CA, Metler RP. Duration of time between exposure and seroconversion in healthcare workers with occupationally acquired infection with human immunodeficiency virus. Am J Med. 1997 May 19;102(5B):115-6.
4. 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(No. RR-11).
5. Vittinghoff E, Douglas J, Judson F, McKirnan D, MacQueen K, Buchbinder SP. Per-contact risk of human immunodeficiency virus transmission between male sexual partners. Am J Epidemiol. 1999 Aug 1;150(3):306-11.
6. Cardo, DM, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med. 1997 Nov 20;337(21):1485-90.
7. Puro V et al., Short-term toxicity and discontinuation of antiretroviral post-exposure prophylaxis. 9th Conference on Retroviruses and Opportunistic Infections, Seattle, February 2002, Abstract 478-M.
8. Beasley RP, Hwang L-Y, Lee G C-Y, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983 Nov 12;2(8359):1099-102.
9. Stevens CE, Toy PT, Tong MJ, et al. Perinatal hepatitis B virus transmission in the United States: prevention by passive-active immunization. JAMA. 1985 Mar 22-29;253(12):1740-5.
10. 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(No. RR-11).
11. Jaeckel, E, Cornberg, M, Wedemeyer, H, Santantonio, T, Mayer, J, Zankel, M, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 2001 Nov 15;345(20):1452-7 .
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