PEP Guidelines

Additional Clinical Considerations

Pregnancy and breastfeeding

The risk of HIV acquisition is increased during pregnancy, and the viraemia that occurs during HIV seroconversion leads to an increased risk of intrauterine HIV transmission.73

Antiretrovirals recommended for PEP can be safely used by people with HIV who are pregnant and/or breastfeeding and are recommended as first-line therapy.

  • Antiretrovirals taken during lactation can enter breast milk and be ingested by the infant. Timely specialist consultation is recommended, however, PEP should not be delayed or withheld in people who are pregnant or breastfeeding. All patients with the potential to conceive presenting for PEP should:
    • have a contraceptive and reproductive history taken to assess risk of pregnancy
    • be offered pregnancy testing (ideally serum beta hCG)
    • be offered emergency contraception if indicated (refer to RACGP Australian Family Physician. Emergency contraception: oral and intrauterine options)87
  • When indicated, follow-up pregnancy testing should occur three to four weeks post-exposure

For further information on the use of antiretrovirals in pregnancy and lactation, refer to the Australian Commentary on the US DHHS Guidelines for the use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents.

Missed PEP doses

Recommendations on whether and when to discontinue PEP after missed doses is largely empirical, informed by the biological and pharmacological properties of each agent, as well as expert opinion. Advice provided to those who miss dose(s) will depend on both the time since the last dose, as well as the number of missed doses. Maintenance of therapeutic levels of PEP differ due to varying pharmacokinetic properties of each PEP agent64,74,75

What to advise patients who miss PEP dose(s):

  • Take the missed dose as soon as possible, unless it is time for the next dose
  • If it is time for the next dose, skip the missed dose and return to a regular schedule
  • Do not take a double dose to make up for a forgotten dose
  • If 72 hours or more have elapsed since the last dose, discontinue PEP
  • If interruption of PEP (for less than 72 hours since the last missed dose) is related to side effects, seek urgent specialist advice
  • Depending on the likelihood of which agent is most likely to be causing specific side-effects, advice may be to stop the third drug and continue two-drug PEP or consider alternative agents.
  • When indicated, follow-up pregnancy testing should occur three to four weeks post-exposure

Individuals at risk of HIV acquisition who decline PEP

There may be several reasons that a patient declines PEP, including:

  • Inaccurate personal risk assessment
  • Concern about medication side effects or long-term toxicities
  • Lack of awareness about the use and likely efficacy of PEP.

Clinicians should address concerns and, where the individual still declines PEP, advise of the maximum 72-hour window-period for starting a PEP should they later reconsider.

Patients with high-risk HIV exposures who decline PEP should be advised to:

  • Have follow-up HIV testing at 6 weeks post-exposure
  • Monitor for HIV seroconversion symptoms: most commonly (in order of decreasing prevalence): fever, fatigue, myalgia, skin rash, headache, pharyngitis, cervical adenopathy, arthralgia, night sweats, and diarrhoea.76
  • Return for assessment if any symptoms are present

Individuals at negligible risk of HIV transmission who request PEP

This response may relate to anxiety and fear about an apparently negligible exposure or to undisclosed more serious risk behaviours. Caution should be taken not to immediately dismiss low-risk exposures, particularly from people from countries with high HIV prevalence or where punitive LGBTIQ and HIV related laws occur. The individual may be fearful of stigma and discrimination when disclosing risk.

Where the HIV risk is truly low, it is recommended not to prescribe PEP to alleviate HIV anxiety, as this may inadvertently reinforce the individual’s belief that the exposure was high enough to warrant PEP and result in further HIV anxiety and presentations for similar low-risk exposures in the future.

It is important that the clinician takes a supportive approach and documents all advice given, including whether PEP was not recommended and whether it was still prescribed at the individual’s request. Early follow-up and a low threshold for psychological and HIV specialist referral is recommended.

People who re-present for PEP after completion of a PEP course

People who present for repeat PEP should be supported, with each presentation assessed on its merits in a non-judgemental manner. Disproportionately higher rates of HIV acquisition occur among people who have previously used PEP.17-19 Unless the exposure is isolated (e.g. an isolated condom failure, high-risk sexual assault), transitioning immediately onto PrEP after the PEP course should be discussed and recommended.

People who re-present with additional high-risk exposure(s) while taking a PEP course

Two-drug PEP and PrEP consist of the same medication, and a subsequent exposure that occurs while someone is on a current course of PEP is similar to an exposure that occurs while taking PrEP. When used for PrEP, co-formulated tenofovir-disoproxil and emtricitabine is proven to prevent HIV acquisition.77,78 From the ANRS Prévenir trial of daily versus on-demand PrEP, extending the PrEP treatment for 48 hours after the last exposure is now known to be highly efficacious for the prevention of HIV acquisition via sex in MSM.79 The iPrEx PrEP trial enrolled the highest number of transgender women to date, and no HIV infections were observed in transgender women whose blood levels were compatible with taking four or more doses of PrEP weekly.80 However, on stratification, PrEP did not provide a benefit for transgender women compared to the overall reduction in HIV incidence in the active study arm. Tenofovir levels decline rapidly after cessation in the vagina and neovagina,60,81,82 so PEP should be continued for seven days after the last high-risk exposure.

There is no empirical evidence to guide clinicians managing people who inject drugs who have a repeat HIV risk exposure whilst injecting drugs during the PEP course. Therefore, extending the PEP course by a further 28 days from repeat exposures is recommended in this situation.

We recommend clinicians follow this advice:
Continue PEP for 48 hours after the last high-risk anal sexual exposure, 7 days after the last high-risk vaginal/neovaginal/front hole exposure and 28 days after the last high-risk sharps or blood exposure.

Individuals who are on PrEP

People taking PrEP as prescribed would generally not be eligible for PEP. However, those at risk of HIV acquisition taking PrEP may present for PEP in the context of suboptimal adherence to PrEP.83 Clinical84 and pharmacokinetic data81,85,86 provide good evidence of levels of adherence to PrEP required to effectively prevent HIV acquisition via anal and vaginal sex. There is little data regarding front hole sex in trans men or neovaginal sex in trans women, but levels of adherence required can be extrapolated from protective tissue concentrations in peripheral blood mononuclear cells.86 The time to protection of tenofovir disoproxil is shortest in lower gastrointestinal tract tissues, followed by peripheral blood mononuclear cells and then female genital tract tissues. Due to persistence of tenofovir and emtricitabine in rectal tissues, levels of PrEP adherence required for protection of HIV acquisition from anal sex are lower than those required for vaginal, front hole or neovaginal sex.

Evaluating the need for PEP involves an assessment of the:

a. site and nature of exposure
b. number and timing of PrEP doses taken in the seven days before the risk exposure
c. correct dosage and timing of on-demand PrEP taken before and after the exposure.

Refer to Table 6 for guidance

Switching from PrEP to PEP is only recommended if:

  • The exposure risk warrants 3-drug PEP, AND
  • The last exposure event occurred within the 72-hour PEP window, AND
  • Adherence to PrEP has been sub-optimal in the 7 days prior to the exposure(s),  

Sub-optimal PrEP adherence is:

  • Less than 4 doses of PrEP in the last 7 days for anal, penile and oral exposures
  • Less than 6 doses of PrEP in the last 7 days for receptive vaginal/neovaginal/front hole sex and sharps/blood exposures

Table 6: Switching from PrEP to PEP

Adherence to PrEPHIV exposure where 3-drug PEP recommendedHIV exposure where 2-drug PEP recommended
Optimal adherence

Daily PrEP:
Has taken PrEP at least 4 days (anal, penile or oral sex) or at least 6 days (receptive vaginal/neovaginal/front hole sex, sharps/blood exposures) in the 7 days prior to the exposure

On-demand PrEP:
Has taken 2 tablets 2-24 hours pre-exposure and 1 tablet 24- and 48- hours post-exposure		Nil action required. Continue PrEP as usual and provide education that when taken as prescribed, PrEP provides protection against HIVNil action required. Continue PrEP as usual and provide education that when taken as prescribed, PrEP provides protection against HIV
Sub-optimal adherence

Daily PrEP:
Has taken PrEP less than 4 days (anal, penile or oral sex) or less than 6 days (receptive vaginal /neovaginal/front hole sex, sharps/blood exposures, in the 7 days prior to the exposure

On-demand PrEP:
Exposure occurred less than 2 hours after loading dose, or missed doses at 24 and/or 48 hours post-exposure)		Transition to 3-drug PEPTake PrEP daily for 28 days post exposure

Transitioning from PEP to PrEP

Many patients who present for PEP have ongoing risk factors for HIV acquisition and so should be recommended to commence PrEP on completion of PEP. Comprehensive information on patient assessment, the prescription of PrEP and follow-up is available in the HIV PrEP Guidelines.

Briefly:

  • PrEP can be prescribed by all medical practitioners and specialised nurse practitioners
  • PrEP can be commenced immediately following completion of PEP
  • HIV serology and recommended testing as per the Australian HIV PrEP Guidelines should be performed on transition from PEP to PrEP

Renal disease

All patients having PEP should be assessed for renal impairment. Tenofovir disoproxil should not be used if creatinine clearance is less than 60mL/min.74 In this situation, tenofovir alafenamide (TAF) is an alternative that may be used. Seek specialist advice about prescribing, as this is not available as a generic formulation.

HBV-positive (HBsAg-positive) individuals

  • People known to have or who are newly diagnosed with HBV infection on baseline testing can be safely commenced on HIV PEP
  • Refer to ASHM Decision Making in Hepatitis B tool.
  • As soon as possible after chronic HBV is identified, collect additional blood for:
    • HBeAg and anti-HBe
    • HBV DNA (viral load)
    • Full blood count
    • Liver function test (LFT)
  • Refer to a clinician experienced in managing HBV as soon as possible (and before completion of the 28-day HIV PEP course) for a decision about treatment discontinuation and follow-up

Individuals who have been sexually assaulted

Those who present due to sexual assault should be assessed for their need for PEP as early as possible after the event. This is ideally done in a specialist sexual assault centre (where specialist counselling and forensic testing can also occur). However, PEP, if indicated, should not be delayed pending referral.

There are no data on HIV prevalence for convicted sexual assailants in Australia; however, from studies on HIV point prevalence in Australian correctional services it ranges between 0 to 0.6%, with most jurisdictions reporting below 0.1%.87

Assaults where there is potential risk of HIV acquisition include penile-anal or penile-vaginal penetration, where the person who committed the assault is known or reasonably believed to be from a region with high HIV prevalence or MSM, or where the assailant is known to have HIV and is not on antiretroviral therapy or is viraemic.

For male-to-male sexual assault PEP is always recommended.  PEP is generally not recommended following heterosexual sexual assault; however, the decision to prescribe PEP should be made on a case-by-case basis. PEP is recommended where an assailant is from a region with high HIV prevalence.

Concerns have been raised that anogenital or oral injuries from a penile-vaginal sexual assault may further increase the risk of HIV acquisition. Given the very low risk of acquiring HIV from a receptive penile-vaginal assault from a heterosexual source in Australia, any additional increase in risk from anogenital injuries or other co-factors would not raise the risk estimate to that in which PEP would be considered.

Emergency contraception should always be offered for people able to conceive in this situation.

Children

All children and adolescents under 18 years of age presenting with a potential risk of HIV exposure should be immediately considered for PEP. In the case of sexual assault, evaluation and treatment should be managed by a multidisciplinary team that is experienced in addressing the medical, psychosocial, and legal issues of such an offence. Clinicians should assess Gillick competency in all cases of underage presentations and determine if parents or guardians are required to be contacted.

Children who are sexually assaulted should be assessed for the risk of acquiring other STIs and the possibility of pregnancy in children who are post-menarche. Emergency contraception should always be offered. The clinician should discuss key issues about PEP with the family and child as soon as possible. Child safety should also be considered. When parental or legal guardian consent is determined necessary but cannot be obtained, PEP treatment may be initiated, with consent strongly recommended to continue PEP beyond the first hours/days.

If PEP is prescribed, ensure sufficient medication is supplied to complete a full 28-day course and that appropriate clinical support, follow-up, and emotional care are available throughout, particularly when the individual is a child or adolescent. Refer to ANZPID guidelines and seek specialist advice.

People incarcerated or working in correctional or detention facilities

People incarcerated in correctional or detention facilities who are potentially exposed to HIV sexually, through injecting drug use or other means require assessment for PEP as soon as possible after exposure. HIV prevalence in Australian correctional facilities is estimated at below 0.1%87, although this data is drawn from small and biased samples and should be used carefully. Timely disclosure of exposure is a limiting factor in these circumstances. The provision of assessment and treatment in correctional facilities should be available across all jurisdictions.

Individuals who commenced PEP overseas

Those who started PEP while overseas may have been prescribed antiretroviral drugs which are not recommended in Australia. Frequently, they may not have had all of the recommended baseline tests and STI/BBV evaluations recommended in Table 4. These should be completed as soon as possible, and the individual should complete the PEP course using an Australian-recommended PEP regimen. This can cause some anxiety to the person seeking care and should be carefully explained, and the individual reassured.

Aboriginal and Torres Strait Islander individuals

HIV prevalence is low (0.1%) in the Aboriginal and Torres Strait Islander population.49 The mode of HIV acquisition differs from non-indigenous Australians, with a higher proportion of indigenous Australians acquiring HIV via heterosexual exposure and injecting drug use.

Provision of culturally safe services for Aboriginal and Torres Strait Islander patients is important in all areas of healthcare, and perhaps even more so for HIV and sexual health-related healthcare. Enquire if the individual has a preference for gender of the clinician conducting the PEP assessment.

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