Introduction

See separate article Needlestick Injury for more information.

Post-exposure prophylaxis (PEP) may be offered for:

• Occupational exposure to hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The management of this risk should form part of an integrated workplace safety plan. Health workers and members of the practice team should be aware of the risk, how to reduce risk and what to do in the event of a needlestick injury.^1,2
• Non-occupational exposure to HBV, HCV and HIV (for example, sexual, paediatric and perinatal).^3,4,5

Rationale for post-exposure prophylaxis

Most of the evidence for efficacy has been gathered from occupational exposure. The evidence base is growing, although further randomised studies are needed.The main areas for consideration are:

• Pathogenesis of HIV infection. This suggests a window of opportunity after infection to prevent viral replication. A combination of primate and human studies suggests PEP is most likely to be effective when initiated as soon as possible (the gold standard is an hour, and certainly within 48-72 hours of infection) and continued for at least 28 days.²
• Efficacy of antiretroviral treatment (ART) in primates. Results are promising and also suggest that early, adequate doses of ART given for long enough are important.⁶
• Evidence of efficacy of ART in humans supports the rationale but some of this work is not directly applicable to occupational exposure studies on HIV-infected pregnant women).
• Assessment of risks and benefits of PEP.

When to prescribe post-exposure prophylaxis

PEP is unpleasant to take and the drugs used have side-effects and toxic effects. This needs to be balanced against the risk of transmission of HIV infection, estimated to be:

• 3/1,000 percutaneous exposures.
• <1/1,000 mucocutaneous exposures.

Risk assessment for occupational exposure²

Risk assessment should be carried out as quickly as possible so that if PEP is deemed appropriate, it can be started without delay. In hospital this is usually done by a designated doctor, trained for the purpose.

An exposure is defined as exposure to potentially infected blood, tissue or bodily fluids through:

• A percutaneous injury.
• Contact with mucous membranes (including the eye).
• Contact with skin that is abraded, inflamed or otherwise not intact.

• Type of exposure. Percutaneous>mucous membrane>skin (skin exposure risk very small, difficult to quantify).
• Body fluid involved - blood carries the highest risk but other body fluids and materials which carry a risk if significant occupational exposure occurs include:
  • Amniotic fluid.
  • Blood.
  • Cerebrospinal fluid.
  • Exudative or other tissue fluid from burns or skin lesions.
  • Human breast milk.
  • Pericardial fluid.
  • Peritoneal fluid.
  • Pleural fluid.
  • Saliva in association with dentistry (likely to be contaminated with blood, even when not obviously so).
  • Semen.
  • Synovial fluid.
  • Unfixed human tissues and organs.
  • Vaginal secretions.
  • Any other body fluid if visibly bloodstained.
• Severity of exposure.
• Disease status of the source patient (there is high risk if at a more advanced stage of disease and if resistant strains of HIV involved). Most source patients in hospital are HIV-negative and rapid testing of HIV status may avoid unnecessary PEP, making it cost-effective.⁵
• Obtaining consent from the source patient may be an ethical minefield. The clinician involved in this task will need to comply with General Medical Council (GMC) guidance and possible consideration of the Human Tissue Act 2004 and the Mental Capacity Act 2005 (or the equivalent legislation in Scotland). Our dedicated separate Needlestick Injury article provides more details on these issues.

• There was visible contamination of device with blood.
• Procedure involved placement in a vein or artery.
• Deep injuries.
• The source patient was suffering from terminal stages of HIV infection.
• Injury was with a hollow-bore needle.

Risk assessment for non-occupational exposure⁵

This includes sexual exposure and exposure through sharing of drug injecting equipment with an HIV-infected source.Transmission via sexual contact depends on several factors, including the viral load of the infected partner, local prevalence, host factors (e.g. menstruation increases risk in vaginal contact) and the type of contact.

Types of contact, in descending order of risk, are as follows:

• Blood transfusion
• Receptive anal intercourse
• Receptive vaginal intercourse
• Insertive vaginal intercourse
• Insertive anal intercourse
• Receptive oral sex (fellatio)

• The risk of HIV transmission is high.
• The exposure is unlikely to be repeated.
• PEP can be started promptly.
• Good adherence is likely.²

• Receptive anal sex.
• Insertive anal sex.
• Receptive vaginal sex.
• Insertive vaginal sex.

• Fellatio with ejaculation.
• Splash of semen into eye.

• Fellatio without ejaculation.
• Cunnilingus.

What to prescribe²

Antiretroviral agents from three different classes of drugs are currently licensed for first-line treatment of HIV infection:

• Nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs).
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
• Protease inhibitors (PIs).
• No antiretroviral drug is currently licensed for PEP, so they have to be prescribed on an 'off-label' basis.
• The starting regime currently recommended by the DH for most patients is one Truvada® tablet (245 mg tenofovir and 200 mg emtricitabine - a combination of NRTIs) once a day plus two Kaletra® film-coated tablets (200 mg lopinavir and 50 mg ritonavir - a combination of PIs) twice a day.
• This regime is suitable for both occupational and non-occupational exposure.
• This regime has been judged to be the most convenient but other antiretrovirals may be more appropriate depending on individual risk factors, tolerance and toxicity, and the results of any sensitivity tests on the infective patient that may be available.
• Completion of 4 weeks of treatment is the goal, although this may be compromised by side-effects . About 50% have significant adverse effects and 30% stop taking the PEP because of this.
• Resistant strains have been detected only rarely when PEP has failed but the relationship of this to exposure to resistant strains is poorly understood.
• The choice of starting regimen can be reviewed at 72 hours if information on the source of infection is awaited but PEP should not be delayed whilst waiting for this further information.²
• In pregnancy, the choice of drug will be more limited.

How to prescribe

• PEP should be initiated according to agreed protocols, usually involving reference to appropriate specialists.
• The protocols and guidelines² should define in detail the procedures to be followed, incorporating assessment of risk, assessment of the PEP recipient, assessment of the source patient, etc.⁵²
• GPs may be more involved in initiating PEP as part of an agreed protocol when caring, for example, for a dying HIV-infected patient at home. Access to advice, drugs and testing should form part of the protocol covering occupational exposure to HIV infection.

Monitoring and follow-up²

• HIV testing (antibody with enzyme immunoassay (EIA), not direct virus assays as these give false positives) should be for twelve weeks after the HIV exposure event or, if PEP was taken, for at least twelve weeks after the PEP was stopped.
• The longer period of monitoring previously advised is no longer supported by evidence unless:
  • The individual is immunocompromised.
  • The illness is compatible with an acute retroviral syndrome (regardless of the interval since exposure).
  • The source patient is dually infected. In the case of HIV and hepatitis C co-infection, delayed seroconversion for HIV (documented at 7 months' post-sexual exposure) has been reported.
• Prompt referral for treatment if patients become HIV-positive.
• Monitoring for toxicity is recommended with baseline FBC, U&Es and LFTs.
• Symptoms such as nausea are very common and should be treated.
• Encouragement to facilitate completion of the course of PEP is important.
• Counselling and education are important:
  • To help with the emotional impact.
  • To educate about breast-feeding, sex, seroconversion, rationale for PEP, etc.^2,5

Failure of post-exposure prophylaxis

Factors cited are:

• Delay in initiation of PEP
• Large inoculum
• Resistant strains of HIV
• Short duration of PEP
• Host factors
• Non-adherence to regime

Practice tips

• Review local policies on needlestick injuries.
• Review practice and local policies on reduction of risk, and prevention of needlestick injuries.
• Review local policies on PEP.
• Inform and educate all practice staff about the policies.

Document references

1. HIV and AIDS: information and guidance in the occupational setting, Health Protection Agency (2008)
2. HIV post-exposure prophylaxis - guidance from the UK Chief Medical Officers Expert Advisory Group on AIDS, Dept of Health (September 2008)
3. HIV and Infant feeding, Dept of Health (2004)
4. Management of HIV in pregnancy, Royal College of Obstretricians and Gynaecologists (2004)
5. Guideline for the use of post-exposure prophylaxis for HIV following sexual exposure, British Association for Sexual Health & HIV (2006)
6. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis, Centers for Disease Control & Prevention (2001)

Acknowledgements