Post HIV Exposure Prophylaxis

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

• Occupational exposure to hepatitis B virus (HBV), hepatitis C (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 needle stick injury.^1,2,3,4
• Non-occupational exposure to HBV, HCV and HIV (for example sexual, paediatric and perinatal)^2,4

Most of the evidence for efficacy has been gathered from occupational exposure. However, sufficiently large studies have not yet been conducted and the rationale has been developed in spite of this.⁵ The main areas for consideration are:

• Pathogenesis of HIV infection. This suggests a window of opportunity after infection to prevent viral replication. Primate models suggest progression of infection to local tissue within 24 hours, to lymph nodes by 24 hours and peripheral blood by 5 days.⁵
• 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.⁵
• Evidence of efficacy of ART in humans support 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.

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:

• 3-6/1000 percutaneous exposures
• 1/1000 mucocutaneous exposures

It is estimated that receptive vaginal exposure to an HIV infected partner carries a risk equivalent to percutaneous exposure, but that receptive anal exposure carries the highest risk.^2,3

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

• A percutaneous injury;
• Contact with mucous membranes;
• 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 carrying greatest risk, but no risk from faeces, nasal secretions, sputum, sweat, tears, urine, vomitus, unless contaminated with blood)
• Severity of exposure
• Disease status of the source patient (High risk if 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.²

Retrospective studies suggest the greatest risk to be from percutaneous exposure to HIV infected blood, especially if:

• Visible contamination of device with blood
• Procedure involved placement in vein or artery
• Deep injuries
• Source patient suffering from terminal stages of HIV infection
• Injury was with hollow bore needle

This includes sexual exposure and exposure through sharing of drug injecting equipment with HIV infected source.
Exposure to receptive anal sex with an HIV infected partner carries the greatest risk. Assessment of risk is much more difficult. Information about the source is likely to be less readily available (especially in cases of rape).
If assessing risk is difficult then it becomes equally difficult to tailor optimum treatment.³PEP is likely to be effective in cases of non-occupational exposure if:

• The risk of HIV transmission is high
• The exposure is unlikely to be repeated
• PEP can be started promptly
• Good adherence is likely³

There is a choice of about 20 drugs from 3 different classes of antiretroviral drugs.

• The choice of drugs is empirical and not equivalent to treatment for 'whole body' infection.
• 2 and 3 drug regimens have been suggested according to level of risk^2,3
• Completion of 4 weeks of treatment is the goal, though this may be compromised by side effects. About 50% have significant adverse effects and 30% stop taking the PEP because of this.²
• Resistant strains have been detected only rarely when PEP has failed, but the relationship of this to exposure to resistant strains is poorly understood.
• Combivir (Combination of zidovudine and lamivudine-ZDV 3TC) is convenient for 2 drug starter packs, with addition of nelfinavir if a third drug is required (indinavir is given less often because of side effects).³
• Once the decision is made to give PEP it should be started as soon as possible (preferably within 24-36 hours of exposure) and without waiting for test results. PEP should be given even 1 week after exposure if the risk is great.²
• 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 waiting for this further information.^2,3
• In pregnancy choice of drug will be more limited.

• PEP should be initiated according to agreed protocols, usually involving reference to appropriate specialists.
• The protocols and guidelines³ should define in detail the procedures to be followed, incorporating assessment of risk, assessment of the PEP recipient, assessment of the source patient etc.^2,3
• 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.² Access to advice, drugs and testing should form part of the protocol covering occupational exposure to HIV infection.

• HIV testing (antibody with EIA, not direct virus assays as these give false positives) at 6 weeks, 12 weeks and 6 months after exposure.
• Additional testing if symptoms suggest seroconversion (flu-like illness).
• Prompt referral for treatment if patients become HIV positive.
• Monitoring for toxicity is recommended with baseline full blood count, urea and electrolytes and liver function testing.
• Symptoms such as nausea are very common and should be treated.
• Encourage(ment) to facilitate completion of the course of PEP is important.
• Counselling and education is important:
  • To help with the emotional impact
  • Educate about breast feeding, sex, seroconversion, rationale for PEP etc.^2,3

Factors cited are:

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

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