As a volunteer additional duty for his EPR, SSgt Homer has been helping the Immunization Clinic give flu shots.  This morning, while giving shots at the BX, he accidentally stuck himself with a needle contaminated with blood from a patient.  You are his supervisor and he comes to you immediately after the incident.  You are a good supervisor and, following the needle-stick protocol in place for your facility, you, SSgt Homer and the patient all go to the ER.  The patient discloses an Infectious Disease physician has carefully monitored him since he was diagnosed with HIV 2 years ago.  He is not on antiretroviral therapy, and a month ago his CD4 count was 400 cells/mm3 and HIV RNA (viral load) was 1,300 copies/mL.

While waiting to be seen by the ER physician, SSgt Homer asks you what his chances are of HIV seroconversion from this one needle stick and if you think he should begin prophylactic antiretroviral therapy (a.k.a. post-exposure prophylaxis = PEP).

What do you tell him?

** THANKS to MAJs (Dr.) Barbara Hoeben and (Dr.) Nicholas Conger for
their help with this Pearl**

Available literature about primary HIV infection indicates systemic infection does not occur immediately after a needle-stick, leaving a brief window of opportunity during which post-exposure antiretroviral intervention might modify or prevent viral replication.

According to the New England Journal of Medicine, the risk of HIV seroconversion of a healthcare provider from a single needle-stick is 0.3%.  However, this risk increases if the injury is deep, if the needle is visibly contaminated with blood, and/or if the patient in whom the needle was originally used dies of AIDS within two months (assumes high viral load and low CD4 count in the infected patient).

Although the risk of seroconversion from a single needle-stick is rare, the CDC guidelines recommend the initiation of PEP as soon as possible. The interval within which PEP should be initiated for optimal efficacy is not known.  Animal studies suggest PEP is likely to be substantially less effective when started more than 24–36 hours post-exposure, but the interval after which no benefit is gained from PEP for humans is undefined.  In addition, the optimal duration of PEP is unknown.

The decision to begin a PEP regimen should be implemented in consultation with persons who have expertise in antiretroviral treatment and HIV transmission.  For most HIV exposures that warrant PEP, a basic 4-week, two-drug regimen is recommended; i.e., zidovudine (ZDV) and lamivudine (3TC); 3TC and stavudine (d4T); or didanosine (ddI) and d4T. Several drug options are available and resistance patterns and potential toxicity of the agents must be taken into account in deciding which option is best.  In previous guidelines, ZDV and 3TC was considered the first choice for PEP because it is available in a combination pill (Combivir®), is taken only twice a day, and has no food restrictions. Although it is still a valid choice, mutations associated with these medications may be common in some patient areas, and therefore, current guidelines allow facilities to make their own choices for PEP regimens (decisions based on resistance patterns in their areas, cost, availability, etc.).  If the source patient is known to be resistant to one or both of the drugs being considered for PEP, other drugs to which the source patient is not resistant should be chosen.  In addition, there are some instances, following high-risk exposure, when the addition of a third drug for PEP is indicated. Be SURE consult your local hospital's ID or public health service for facility-specific procedures IMMEDIATELY. PEP is best started right away IF INDICATED. The experts in your facility can help determine whether or not PEP is indicated.

To assist with the initial management of an HIV exposure, health-care facilities should have drugs for an initial PEP regimen pre-selected and available for use.  In addition, access to infectious disease specialists for unique circumstances (i.e., health-care worker exposed is pregnant, an unknown source patient, etc.) may also be aware of resistance patterns in the patient population in a given area is critical.  (Refer to your facility’s needle-stick protocol and the references below for specific guidance.)  Understandably, there are no studies examining the effectiveness of PCP.  Several thousands of exposed healthcare providers would need to enroll in a prospective trial to achieve the statistical power necessary to directly demonstrate PEP efficacy.

Of course, not to scare Homer but to be thorough, you also need to discuss that needle-stick injuries do not only expose one to a risk of HIV infection, but also hepatitis B (HBV) and, to a lesser extent, hepatitis C (HCV):

As with HIV, the risk of HBV depends on the degree of contact with infected blood and the status of the source patient.  According to a 1982 article in the Annals of Internal Medicine, the risk of developing clinical hepatitis if the source patient is both hepatitis B surface antigen (HBsAg) and HBeAg-positive is 22-31%; the risk of developing serologic evidence of HBV infection was 37-62%. By comparison, the risk of developing clinical hepatitis from a needle contaminated with HBsAg-positive, HBeAg-negative blood is 1-6%, and the risk of developing serologic evidence of HBV infection, 23-37%.  Therefore, Homer should be tested for HBV and given the hepatitis B vaccination series.  In addition, an infectious disease specialist should be consulted regarding the use of hepatitis B immune globulin (HBIG).  The initiation of HBIG within one week of needle-stick exposure to HBsAg-positive blood can provide an estimated 75% protection from HBV infection. The good news is that the risk of hepatitis C (HCV) infection is low. The incidence of infection with HCV via needle-stick injury is in the range of 0-7%.  The Advisory Committee on Immunization Practices (ACIP) states the use of immune globulin for post-exposure prophylaxis is not supported by the available literature.   In addition, the use of antiretroviral agents (i.e., interferon) to prevent infection, are not FDA-approved for this indication.

A good rule of thumb to remember the risk from a needle-stick exposure is:

-    HBV = 30%
-    HCV = 3%
-    HIV = 0.3%
 

References:

Alter MJ.  Occupational exposure to hepatitis C virus: a dilemma. Infect Control Hosp Epidemiol. 1994;15:742-4.

Cardo DM, Culver DH, Ciesielski CA.  A case-control study of HIV seroconversion in health care workers after percutaneous exposure.  N Engl J Med. 20 Nov 1997;  337(21):1485-90.

Grady GF, Lee VA, Prince AM, et al.  Hepatitis B immune globulin for accidental exposures among medical personnel: final report of a multi-center controlled trial.  J Infect Dis.  1978;138:625-38.

Prince AM, Szmuness W, Mann MK, et al.  Hepatitis B "immune" globulin: effectiveness in prevention of dialysis-associated hepatitis.  N Engl J Med.  1975;293:1063-7.

Seeff LB, Zimmerman HJ, Wright EC, et al.  A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis: a Veterans Administration cooperative study.  Gastroenterology.  1977;72:111-21.

U.S. Department of Health and Human Services.  Centers for Disease Control and Prevention.  Updated U.S. public health service guidelines for the management of occupational exposures to HBV, HCV, and HIV. MMWR.  29 June 2001; 50(RR-11).

Werner BG, Grady GF.  Accidental hepatitis-B-surface-antigen-positive inoculations: use of e antigen to estimate infectivity.  Ann Intern Med. 1982;97:367-9.

This Pearl is meant for academic and educational purposes only. This Pearl is meant to raise important points regarding the safe and cost-effective pharmacotherapy of patients. It is not meant to be the definitive reference for the treatment or prophylaxis of various diseases. Although every effort is taken to ensure this Pearl is correct and factual, errors may occur. The Pharmacoeconomic Center assumes no liability for incorrect information or harm that may occur from the use of the information included in this Pearl.