3.1 MANAGEMENT OF ACCIDENTAL PERCUTANEOUS EXPOSURE TO HIV
Percutaneous or mucosal exposure to HIV-contaminated blood or body fluids in health care setting is a rare but recognized mode of HIV transmission. It has been estimated that the average risk of infection after percutaneous exposure is 0.3%1 whereas that of mucosal membrane exposure is about 0.09%.2 As of end of December 1999, 102 definite and 217 possible occupationally acquired HIV (OAI) infections had been reported globally.3 Amongst these OAI, nurses and doctors were the most frequently implicated health care workers (HCW). Nevertheless, although OAI occurs, it accounts for just a fraction of the known HIV infections in HCW and therefore plays an infinitesimal role in the global HIV epidemic.
Attempts have been made to prevent HIV infection by the percutaneous route through administration of antiretroviral chemoprophylaxis, before or after exposure. Evidence of its effectiveness is available in both animal and human studies. In chimpanzees receiving nevirapine, HIV-1 challenge did not result in infection.4 In another animal model, antiretroviral drug given after simian immunodeficiency virus (SIV) exposure prevented virus transmission.5 In humans, a case-control study of health care workers who sustained mainly percutaneous injury also found efficacy of zidovudine in protecting against seroconversion.6
Despite the small absolute risk of infection, occupational exposure to HIV in health care setting could pose a significant psychological burden to the injured. Post-exposure management offers a unique chance for therapeutic prevention of HIV infection. Humane counseling, professional advice, together with appropriate treatment shall aim at minimizing psychosocial as well as physical morbidity consequent to the exposure. Currently, management of potential exposure to HIV has been one major focus of the scope of Accident & Emergency Departments and HIV care units in Hong Kong. Exposure to known HIV-infected patients is rare and a handful of post-exposure prophylaxis has been prescribed over the last years. There was no known incident of seroconversion upon accidental exposure in health care setting locally.
Primary prevention of occupational exposure to blood or body fluids is crucial. Adherence to standard infection control practice minimizes the occurrence of injury. Some 'accidents' are avoidable. Universal precautions protect HCW from blood-borne diseases beyond HIV, irrespective of the HIV status (whether known or unknown) of those involved.
The management of an incident of occupational exposure involves proper risk assessment, counselling tailored to the need of individual client, and the prescription of antiretroviral drugs to prevent HIV transmission if the risk is substantial. These are discussed in the following sections. An algorithm is provided at the end of the Chapter.
I. Risk assessment of exposure
HIV transmission can potentially occur in the event of a significant exposure to body fluids/tissues (e.g. blood, cerebrospinal fluid) which may harbor infectious blood-borne viruses from an HIV/AIDS patient. Risk assessment is the most important component of post-exposure management and should be commenced as soon as possible after exposure. The risk of transmission depends on (i) type and extent of exposure, and (ii) HIV status and stage of the source. In assessing the exposure, multiple factors need to be considered:
Some factors of the accident itself are associated with a higher potential of seroconversion after percutaneous exposure to HIV-infected blood:6
No matter how extensive the exposure is, HIV transmission may only happen if the source is HIV infected. For known infected source, his/her stage of disease has bearing on the risk of transmission. It is, however, not uncommon that HIV status of the source is unknown or cannot be ascertained. In this case, the likelihood of HIV infection in the source shall be assessed by clues such as (a) HIV-related illnesses, e.g. Pneumocystis carinii pneumonia, oral thrush, (b) HIV-related risk behaviors, e.g. unprotected sex, multiple sex partners, needle-sharing for drug injection, and (c) HIV prevalence of the community group which the source belongs to. Re-evaluation of the exposed person should be considered if there is additional information after the first assessment, e.g. HIV status of source.7
II. Counseling and health advice
Counseling and psychological support is another crucial component of post-exposure management. This is often provided by the nursing as well as medical staff. The assessment and the determination of the risk of HIV transmission would provide a good case-by-case base for further counseling. A variety of areas need to be covered, including: general risk of infection after percutaneous or mucosal exposure, assessment of the specific exposure, usefulness and limitations of PEP, necessary investigations, necessary precautions, arrangement of follow-up care and others.
In counseling for HIV antibody testing, one might need to explore if the injured is already at risk of HIV infection before injury. Any previous HIV antibody testing and its results should be inquired. This is particularly relevant if PEP has to be prescribed. For infected individuals, the antiretroviral prophylaxis (regimen similar to antiretroviral therapy) will actually be treatment of the disease. A thorough assessment and plan would be a must for optimizing antiretroviral therapy for any infected patient.
All cases with potential risk of infection have to be warned about HIV seroconversion illness, for which they should seek medical consultations. This typically occurs 2-6 weeks after exposure. (see Chapter 4.5) Classical symptoms are fever, skin rash, sore throat, swollen lymph glands especially on neck, and ulcers in mouth/genitalia. Sometimes, it can just be non-specific symptoms such as fever, headache or malaise. Also, there was report of delayed HIV seroconversion (8 to 9.5 months after exposure) in a health care worker who contracted both HIV and HCV after a needle-stick injury.8 Thus, symptoms suggestive of acute HIV infection should not be discarded lightly especially in the case of delayed presentation.
Similarly, the injured should be advised to take precautions while pending outcome of the exposure, if risk of HIV infection exists. For example, he/she should practice safer sex and not donate organ, blood and semen. Female should avoid pregnancy.
III. Blood investigations
A baseline HIV antibody test is needed for most of the injured. Its result serves as a reference for interpreting subsequent testing results, in case there is seroconversion after the exposure. Also, it can exclude an underlying HIV infection. One option is to test for HIV antibody only when subsequent follow-up blood samples are tested antibody positive. However, a baseline antibody test must be performed immediately if underlying HIV infection is suspected when an injured is put on PEP. In such circumstance, baseline blood investigations of complete blood picture (CBP), renal/liver function tests (R/LFT) and sugar (if protease inhibitor given) should be performed concurrently. Creatinine kinase and amylase are optional. Baseline investigations for viral hepatitis B and C shall also be pursued as appropriate for the injured.
In some cases, testing of source patient for HIV antibody might assist in the management of the injured. This should however be done after clear explanation of the rationale to the source and consent obtained. Confidentiality should be upheld throughout.
Follow-up investigations depend on whether the injured has been put on PEP. For those who are not on HIV PEP, they can be followed up 3-6 months after the initial assessment and consultation. For those on PEP, clinical and biochemical (CBP, R/LFT, amylase, CPK, sugar (if protease inhibitor is prescribed)) monitoring for drug tolerance at week 0,2,4, and third month should be considered.
Follow-up HIV antibody test shall be performed at month 6. A test earlier at month 3 is optional. An additional month 12 testing may be considered case-by-case for high infection risk cases who have taken PEP, for fear of the possibility of delayed seroconversion. HIV antibody testing and HIV RNA are performed for cases presenting with suspected seroconversion illness. Plasma shall be stored for resistance testing in such case.
IV. Post-exposure prophylaxis
IV.A The scientific evidence
Pathogenically, there is time lag between HIV exposure, viral seeding, replication and systemic infection. Antiretrovirals may theoretically be able to intervene by inhibiting viral replication after exposure. Both animal and human studies have provided evidence for the efficacy of PEP. From animal studies, it has been demonstrated that size of the inoculum, timing and duration of PEP affects chance of infection. Success of post-exposure prophylaxis (PEP) depends on its early initiation. PEP initiated at 72 hours after exposure in animal models was often ineffective. A retrospective case-control study on health care workers revealed that after controlling for other factors, there was a 81% (95% confidence interval, 48-94%) reduction in risk of infection with the use of zidovudine (AZT) after percutaneous exposure.6 The efficacy of abbreviated postpartum regimens initiated after childbirth in reducing mother-to-child HIV transmission also provides support to the principle of PEP. Nevertheless, PEP is definitely not fool-proof, and failure of antiretroviral prophylaxis has been reported in both animal and human studies.
Given the small absolute risk of HIV transmission even with significant exposure to HIV-contaminated blood or body fluids, the prescription of PEP depends on a balance of risks and benefits, which should be explained clearly to the injured. Potential drawbacks of PEP include: toxicity of antiretrovirals, unknown long term effects in HIV positive and negative people, uncertain level of effectiveness, development of resistance, and unknown impacts to the course of disease if seroconversion occurs. Potential benefits of PEP are: reduction of the chance of infection for injury with significant risk.
IV.B The recommended regimens
Though only zidovudine has been demonstrated to be effective in clinical studies, combination antiretroviral PEP is now recommended (based on data from treatment of HIV-infected patients) for its greater suppression of viral replication, broader coverage of resistance strains, and thus the theoretical advantage of more effective prevention of HIV transmission. When indicated, PEP should be initiated as soon as possible.
The US CDC recommended a basic 2-drug regimen of AZT (200 mg tid or 300 mg bid) and 3TC (150 mg bid) for cases with risk of infection.9 The tablet of Combivir (AZT 300 mg +3TC 150 mg) can be considered and given bid. A protease inhibitor (PI) such as indinavir (800 mg Q8H) or nelfinavir (750 mg tid) is added in an expanded 3-drug regimen if there is higher risk for transmission.9 However, UK authority generally favored a 3-drug PI-containing (indinavir, followed by nelfinavir) regimen for all exposures where PEP is indicated.10 There is insufficient evidence to support whether the US differentiated 2-drug/3-drug approach or the UK blanket 3-drug approach is superior. Decision should be made on a case-by-case basis, balancing against such factors as assessed risk, anticipated PEP efficacy and potential toxicity and tolerance for the injured.
The PEP regimen might need to be modified accordingly if resistance is known or suspected in source HIV strains. Suspicion is usually based on (a) failure of treatment in source, (b) prevalence of primary resistance in the locality, or (c) documented resistance by resistance assays. Evaluation of the treatment history and efficacy of the current regimen in the source patient is a must.
Lately, the US CDC suggested that nucleoside reverse transcriptase inhibitor other than AZT and 3TC could be considered, e.g. stavudine (d4T), didanosine (ddI).7 Other drugs such as efavirenz or abacavir can be the alternative for the third drug in the expanded regimen. However, the limited experience of using these alternative drugs for PEP shall be taken into account when choosing the regimen. The use of nevirapine to spare PI has caused severe morbidity and even deaths, which is thus contraindicated in PEP.11
The dosage of common antiretrovirals and the potential side effects are in Box 3.1. Potential interactions of antiretrovirals with drugs that the injured is taking should be borne in mind. Special considerations are needed for those who are pregnant. For example, efavirenz is contraindicated because of its teratogenecity and indinavir should be avoided in late pregnancy for hyperbilirubinemia in newborn.
The optimal duration of PEP is unknown but a complete course is normally 4 weeks. This is prescribed in no less than 2 separate visits. Many HCWs who took PEP experienced one or more symptoms and a substantial proportion could not complete the course.12,13 Pretreatment counseling of all potential side effects might hopefully improve compliance of PEP. Besides blood investigations, toxicity should be evaluated clinically and managed accordingly. The best efforts should be made to have the exposed person complete the 4-week course if PEP is indicated. For PEP prescribed for unknown source who is subsequently found HIV negative, the PEP should be stopped.
References