Post-Exposure Prophylaxis (PEP) guidelines for children and adolescents exposed to blood-borne viruses

Authors: Guide information
Gareth Tudor-Williams
Djamel Hamadache
Caroline Foster

Date of preparation:June 2003
Date reviewed: February 2011
Next review date: February 2012

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Following exposure to blood-borne viruses, it should be remembered that the risk of transmission is highest for Hepatitis B, then Hepatitis C and then HIV. As this document has been prepared for the CHIVA website its focus is on HIV. However, it is important to consider risk of pregnancy and sexually transmitted infection if there has been a sexual assault.

Hepatitis B post-exposure immunisation is most effective if started within 48 hours of exposure, however may be beneficial upto a week after.

HIV PEP is most effective if started within 1 hour of exposure, but may be beneficial up to 72 hours after.

Background

The risk of community acquired HIV in children is extremely low. However, children and adolescents are potentially at risk of contracting HIV from a variety of exposures, including needlestick injury, sexual abuse, consensual sexual activity in adolescence, biting or being bitten by another child, playground or sports field injuries, etc.1 There have been no reported school-related transmissions.

The HIV status of the source is usually unknown and difficult to establish. Body substances presenting a risk of HIV transmission include blood, breast milk, amniotic fluid, semen or any body fluid if visibly bloodstained.2 The risks of HIV being transmitted from a variety of exposures are shown in Table 1. HIV-infected fluids cannot penetrate intact skin. Sexual abuse represents a particular risk because of possible multiple exposures, mucosal trauma and the cervical ectopy and vaginal epithelial thinness found in children.3 Up to 40% of 15 year olds in the UK are sexually active. Following the widespread use of HAART (Highly Active Antiretroviral Therapy) children with perinatally acquired HIV-1 infection are surviving into adolescence and entering sexual relationships with their HIV negative peers who may present for PEPSE (Post Exposure Prophylaxis following Sexual Exposure). Please refer to BASHH Guidelines http://www.bashh.org/documents/58/58.pdf 4.

Table 1. Risks of HIV transmission from different exposures,5,6,7,8,9

Type of HIV exposure Source HIV status
Status unknown HIV positive
  London Rest of UK  
Occupational needlestick injury that punctures skin IVDU: 0.3% or 1 in 333
0.014% or <1 in 7000 0.0028% or 1 in 36,000
Man having unprotected receptive anal sex 0.45% or 1 in 222 0.09% or <1 in 1000 3% or 1 in 33
Woman having receptive vaginal intercourse 0.009% or <1 in 10,000 0.0018% or <1 in 55,000 0.2% or 1 in 500

*Risk of HIV transmission = Risk that source is HIV positive x Risk of exposure

IVDU HIV seropositivity rate in London in 2009 was 4.1% (several fold higher than rates in rest of UK).13 Given a 0.32% risk of transmission if the source was HIV positive, the risk from a community acquired needle stick injury can be assessed as about 1:10,000 in London to less than 1:50,000 elsewhere. Note that quoted risks are based on injuries from needles contaminated with fresh blood: old blood in a syringe and needle found in the park is likely to carry a lower risk of transmission. Be aware that reddish/brown fluid in the hub of needles is more likely to be from previously heated drugs than to be blood

Mechanism of action of HIV PEP

The presumed mechanism for HIV PEP is that shortly after an exposure to HIV a window period exists during which antiretroviral medications may help to diminish or end viral replication. In a small case controlled study, AZT reduced the transmission rate of HIV by 79%.11 In addition, a prophylactic effect of AZT alone and in combination has been shown to reduce vertical transmission of HIV from mother-to-child.7 The Department of Health recommendations for PEP in adults are Truvada (a combination of tenofovir + emtricitabine) and Kaletra (lopinavir/ritonavir), a reflection of the rapid genital tract penetration of Tenofovir and efficacy of Truvada/Kaletra against most current viral isolates in the UK.12 There are no DOH recommendations for PEP in children.

The risk of transmission of Hepatitis B (HBV) and Hepatitis C (HCV) from a community acquired needle stick injury are significantly higher than for HIV.
UK seroprevalence data for blood-borne infections in intravenous drug users in 2009 reported13:

  London Outside London
HIV Prevalence 4.1% 1.5%
HBV Prevalence 32% 17%
HCV Prevalence 59% 47%

The risk of HBV seroconversion following a needle-stick from known high risk HBV infected source (HBe Ag +ve) is 37-62%14 and around 5% following needle-stick from a known low risk HBV infected source (HBe Ag –ve). The average HCV seroconversion rate following needle-stick from known HCV positive source is 1.8%

Data for risk of transmission of HBV or HCV from single sexual exposure are not robust. HCV is inefficiently transmitted. Risks from high risk HBV infected source may be as high as 50% for seroconversion (lower for clinically symptomatic HBV infection).

Given the safety of HBV vaccination, the risk-benefit ratio favours vaccinating all exposed children, following needle stick injuries or sexual assault. Baseline testing and 3-month serological follow-up testing for HCV and HBV are recommended. It is sufficient to request HCV IgG, and HBV IgM, HBsAg, HBsAb and HBcAb.

Procedure for Children and Adolescents presenting with possible exposure to HIV

Risk assessment
Careful history and examination to assess the risk of exposure to HIV. Establish whether exposure occurred within the last 72 hours.

a). No risk e.g.

  • intact skin visibly contaminated with blood or body fluids
  • kissing
  • casual touching

Action

  • Reassure parents and child
  • Discharge

b). Low risk e.g.

  • mucous membrane or conjunctival contact with blood or body fluids
  • superficial injury that does not draw blood
  • associated with needle/instrument not visibly contaminated with blood or body fluid

Action

  • Counsel family about risks of HIV, HBV and HCV transmission
  • Recommend standard HBV immunisation: Day 0, 1 month, 6 months (or booster if already immunised)
  • PEP not recommended (explain risks of HIV PEP drug side effects (see table 2) which outweigh the extremely low risk of HIV transmission).

c). Moderate risk e.g.

  • skin penetrating injury that draws blood by needle/instrument contaminated with blood or body fluid
  • wound causing bleeding and produced by sharp instrument visibly contaminated with blood
  • sexual intercourse with individual of unknown HIV status.

Action

  • Counsel family about risks of HIV, HBV and HCV transmission
  • Recommend accelerated HBV immunisation: Day 0, 1 month and 2 months (or booster if already immunised)
  • Discuss risks of HIV PEP (see table 2)
  • Consider HIV PEP but on balance the risk of drug side effects from PEP probably outweigh the benefit. However, it is generally considered that transmission of HIV is likely to be increased following aggravated sexual intercourse, such as that experienced during sexual assault. Clinicians may therefore consider recommending PEPSE more readily in such situations

d). High risk e.g.

  • Significant exposure to blood or body fluids from source known to be HIV, HCV or HBV infected

Action

  • Counsel family about risk of HIV, HBV and HCV transmission
  • Recommend accelerated HBV immunisation: Day 0, 1 month and 2 months (or booster if already immunised)
  • Consider HBV Ig if source is a highly infectious HBV carrier and child is susceptible (see below, under Management)
  • Discuss risks of HIV PEP (see table 2)
  • Recommend starting Standard HIV PEP (later modifications may be required dependent on source's current viral load, treatment history and viral resistance).

2. Investigations

Source
In rare situations the source may be known and if the individual gives consent HIV, HBV and HCV serology may be tested. If the source is already known to be HIV positive, obtain details of present and past antiretroviral medications and consider resistance testing, although the latter should not delay commencement of PEP. Most virologists now do NOT recommend testing of source materials such as needles found in public places, since the test results are of low sensitivity and should not be used to guide management.

Child/Adolescent
Obtain baseline HCV, HBV and HIV antibody status. If antiretroviral therapy is to be started also request FBC, U&E and LFTs. Ascertainment that the child / adolescent is not already HIV infected is important, as treatment with PEP in that circumstance would be inappropriate. The baseline HIV test result on the child/adolescent should be available at the first follow up visit. Baseline Point of Care testing (POCT) is not recommended in this situation.

3). Management

HIV PEP
HIV PEP is most effective if started within 1 hour of exposure, but may be beneficial up to 72 hours after. The child's family should be counselled about likely side effects (Table 2) and given contact phone numbers in case of concerns during or after the treatment period. An appointment to see a paediatrician/HIV physician on the next working day and ideally within 72 hours of starting HIV PEP should be made. Initially 5 days of PEP should be prescribed. A further prescription for a total of 4 weeks should be given at consultant review if PEP to be continued. PEP regimens may sometimes need modification if the index case is known to or likely to harbour drug resistant virus. Seek expert help but do not delay starting PEP.

Regimens
Accurate weight and height measurements should be used to calculate doses.

Surface Area Calculation

BSA(m²) =√(weight (kg) X Height (cm)

3600

Children under 40kg (and adolescents >40kg unable to swallow tablets): triple therapy with Zidovudine, Lamivudine and Kaletra.

Children and adolescents over 40 kg (able to swallow tablets): triple therapy with Truvada (Tenofovir and Emtricitabine) and Kaletra. An alternative for Truvada, for a child with renal insufficiency is Combivir (Zidovudine and Lamivudine).

Table 2 HIV PEP Drugs, Doses and Side effects.

Drug Formulation Dose Side Effects*
Zidovudine (AZT, ZDV) (for child < 40Kg) Cap 100mg(white with blue line)/250mg (White/Blue)
Liq: 10mg/ml
180mg/m2 /per dose BD to a maximum dose of 250mg BD Granulocytopenia and/or anaemia, nausea, headache, myopathy, hepatitis, nail pigmentation, neuropathy.
Lamivudine (3TC) (for child < 40Kg) Cap: 100mg (orange), 150mg (white)
Liq: 10mg/ml
4mg/kg / per dose BD to a maximum dose of 150mg BD Peripheral neuropathy, nausea, diarrhoea, headache,
Combivir (3TC, ZDV) (for child >40kg) Combined Tab: ZDV 300mg/3TC 150mg (white) ONE (1) tablet BD As for ZDV and 3TC
Truvada (TDF+FTC) (for child >40kg) Combined tablet: Tenofovir 245mg & Emtricitabine 200mg (blue) ONE (1) tablet OD

Headache, diarrhoea, nausea, vomiting, renal tubular dysfunction, bone demineralization
Do not use if known renal impairment

Kaletra (LPV/rtv) Adult tablet: Lopinavir 200mg & Ritonavir 50mg (orange)
Paediatric tablet: Lopinavir 100mg & Ritonavir 25mg (yellow)
Liq: Lopinavir 80mg/ml +Ritonavir 20mg/ml

Lopinavir 230mg/m2 /per dose BD to a maximum dose of 5mls liquid BD, or 2 adult tablets BD, or 4 paediatric tablets BD.

Child: (≥2 yrs): 230mg/m2
BD (0.6 - 0.8m2): 200mg
BD; (0.8 - 1.2m2): 300mg
BD; (1.2 - 1.7m2): 400mg
BD; (≥1.4m2): 400mg BD

Dose in ml = 230 × SA/80
Adult:(400mg BD) = 2
tabs BD = 4 paed tabs BD
= 5ml BD of solution
**All doses based on LPV**

Diarrhoea, abdominal pain nausea, vomiting, headache

*This list of side effects is not exhaustive – refer to product datasheet for detailed information on side effects, interactions with other medicines and other cautions for use.

Table 3. Kaletra Dosing by surface area

Body Surface Area (m2) Recommended number of tablets
100/25 mg (Paediatric) tablets
200/50 mg (Adult) tablets
0.5 to < 0.9 m2 2 paediatric tablets (2 x 100/25 mg) BD
0.9 to < 1.4 m2 3 paediatric tablets (3 x 100/25 mg) BD
1.4 m2 or greater

4 paediatric tablets (4 X 100/25 mg) BD

Or 2 adult tablets (2 X 200/50 mg) BD

In addition an anti-emetic such as domperidone and an anti-diarrhoeal such as loperamide should be prescribed for prn use in the event of GI side effects (see BNFC).

HBV
For a significant exposure to an unknown source an accelerated course of HBV immunisation (Day 0, 1 month and 2 months) should be offered. The HPA recommends the use of intramuscular hepatitis B immunoglobulin only if the source is known to be HBV infected, although would agree to its use with an unknown source if compelling circumstances existed.

NB: For those children / families with difficulty accessing services, vaccinating at the HIV PEP follow-up, 0, 14 and 28 days checking the serological response at 3 months, is a reasonable compromise (expert opinion).

HCV
There is no recognised PEP for HCV. Families may be counselled that, in the event of HCV seroconversion, therapy is increasingly successful.

Tetanus
The need for Tetanus injection/booster should be assessed per usual practice

4). Emergency contraception and screening for sexually transmitted infections

Following sexual exposure it is important to consider emergency contraception (pubertal girls) and the need for screening/prophylaxis for other sexually transmitted infections. See Local/BASHH Guidelines.4

NB: Children under 18 presenting with non-consensual sexual activity should be referred to the Child Protection Co-ordinator.

5). Follow-up

Prior to discharge from A&E families embarking on HIV PEP should have the following:

  • An outpatient appointment, preferably within the next 72 hours to see a named clinician with experience in prescribing antiretroviral drugs
  • Contact telephone numbers in case of concerns about any aspect of the HIV PEP
  • 5 days of Antiretroviral therapy (with anti-emetic and anti-diarrhoeal for prn use)
  • A letter for their GP, with patients/parents consent

Outpatients Visits
Within 72hrs:

Review in clinic, assess adherence and toxicity, decide whether PEP should continue for the full four-week course. Document and give baseline HIV, HBV, HCV Ab results. Arrange psychological support as necessary.

Day 14: Review in clinic, assess adherence and toxicity, check FBC, U&E, LFTs.

Day 28: Review in clinic, assess adherence and toxicity, check FBC, U&E, LFTs (if abnormalities on previous blood tests).

1 month and 3 months AFTER PEP completion:

Follow-up HIV testing should be undertaken with a fourth generation combined HIV antibody/ antigen assay. Antibody screening for Hepatitis B and C is also recommended at 3 months following exposure. If further HBV vaccination required arrange appropriate follow up (either clinic or GP based).

Acknowledgments

With thanks to Dr Hermione Lyall (Consultant in Paediatric Infectious Diseases), Nicola Husain (HIV Pharmacist) and David Muir (Consultant Virologist).