This guideline outlines the updated Australian recommendations for human immunodeficiency virus (HIV) post-exposure prophylaxis (PEP) following potential or known exposure to HIV in sexual, occupational, and non-occupational settings. Risk of transmission, the timing of PEP, baseline assessment, preferred regimen and follow-up are outlined, including the use of PEP in the era of the Pharmaceutical Benefits Scheme (PBS)-subsidised HIV pre-exposure prophylaxis (PrEP). This guideline is not intended to be prescriptive or replace specialist advice in the provision of PEP. Every presentation for PEP should be assessed on a case-by-case basis, balancing the potential harms and benefits of treatment.
It is anticipated that the guideline will support development of local policy and procedures, acknowledging the diverse healthcare systems in each Australian jurisdiction. The guideline recommendations generally apply to people aged 14 years or older. For paediatric PEP prescribing guidance, refer to the section: Children younger than 16 years of age. Paediatric PEP assessment and prescription require specialist advice.
Presenting for PEP and disclosing HIV risk activities can be a stressful experience. It is important that clinicians are non-judgemental when assessing patients for PEP. A patient’s negative experience when requesting PEP has resulted in failure to re-present for PEP leading to subsequent HIV infections.1,2
To be effective, initiation of PEP must occur within 72 hours of exposure to HIV; the earlier the better, and ideally, within 24 hours.
PEP is usually provided free-of-charge via hospital (but not community) pharmacies, emergency departments, and HIV and sexual health clinics. Community pharmacy PEP costs and the ability to dispense PEP immediately will vary in each jurisdiction.
New to the Guidelines
- The recommended first-line two-drug post-exposure prophylaxis (PEP) regimen is co-formulated tenofovir disoproxil and emtricitabine, with the addition of dolutegravir 50 mg daily OR raltegravir 1200 mg daily for 28 days when three-drug PEP is recommended
- Advice on how to privately prescribe two-drug PEP at a reasonable cost is provided for general practitioners (GPs) who are not authorised to prescribe human immunodeficiency virus (HIV) s100 drugs
- Rilpivirine is no longer recommended for three-drug PEP
- PEP starter packs are discouraged; the full 28-day course should generally be provided at the initial consultation
- Because most Australian people with HIV are on antiretroviral therapy with an undetectable viral load, the prevalence of detectable HIV viraemia in the source population has been used to determine HIV transmission risk where the source HIV status is unknown
- A new source category of men who have sex with men and who inject drugs has been added in recognition of the higher proportion of this group who are viraemic than those men who have sex with men who do not inject drugs in Australia
- Removal of the arbitrary, non-evidence-based, numerical thresholds at which PEP was indicated and replacement with advice to guide an individual risk-benefit assessment
- Further guidance on the generally low-risk scenario of human bites is included.
- All children younger than 16 years of age who qualify for HIV PEP are recommended to receive combination therapy with three drugs. This strategy differs from the risk-stratified approach used in adults, where two or three drugs may be considered depending on the risk-exposure event.
- For PEP in children, a single fixed drug-combination option is now provided (Biktarvy®) which may improve compliance.
Important note for general practitioners who have not previously prescribed HIV PEP
Traditionally the medication used for two-drug PEP (tenofovir disoproxil 300 mg co-formulated with emtricitabine 200 mg) has only been available by prescription by emergency departments, sexual health clinics, HIV specialists or other accredited HIV s100 prescribers. The medications used are not Therapeutic Goods Administration (TGA) approved for this indication and are not PBS listed, making the historical cost prohibitive while the drugs remained patent protected.
The availability of generic formulations of tenofovir disoproxil 300 mg and emtricitabine 200 mg, largely used for PrEP, now make it possible for any prescriber to provide a private prescription for this two-drug PEP, available at a reasonable cost (at the time of publication: approximately $40-50 for a one-month course).
Please follow the guidelines outlined in this document to assess if your patient fits the recommendation for two-drug PEP and, if unsure, contact your local PEP telephone support line. If two-drug PEP is indicated, after the baseline tests, you can write a prescription for PrEP to be used as PEP, or alternatively, write a private prescription and arrange follow-up.
As generic formulations are not currently available for the recommended third drugs in PEP, if the patient requires three-drug PEP, please consult your local specialists (Sexual Health, HIV, Infectious Disease or Immunology) for advice.
Local telephone support is available here for PEP prescribing in each Australian jurisdiction.
Background: evidence supporting the efficacy of PEP in preventing HIV acquisition
There are currently no data from randomised controlled trials that provide evidence of the efficacy of PEP in preventing HIV acquisition. Animal data have been particularly informative regarding the importance of starting PEP as early as possible following an exposure event, the 72-hour post-exposure window-period for starting PEP and the 28-day duration of the course.3-7
Evidence for the use of PEP has also been extrapolated from data from birth parent-to-child transmission, where PEP given to a neonate significantly reduced their risk of HIV acquisition when the birth parent was not virally suppressed on antiretroviral therapy at delivery8,9 and following occupational exposures,10 where the risk of HIV acquisition was reduced overall by 81% in the original case-control study of PEP.11
The only clinical effectiveness study of PEP in humans was performed among 200 Brazilian high-risk HIV-negative men who have sex with men (MSM). Seroincidence in the cohort was very similar to that expected in the population. There was no difference in PEP efficacy, likely due to a lack of statistical power. However, HIV seroconversions were only 1/68 in the PEP group compared with 10/132 in the group not receiving PEP.12
Although PEP is likely to be highly effective when initiated in a timely manner, taken as prescribed, and thus avoiding further risk exposures, there have been documented HIV seroconversions after PEP after both sexual and occupational exposures.
In Australian13 and international14,15 observational studies, seroconversions subsequent to a PEP course following sexual exposures were most commonly associated with ongoing risk behaviours. Other reasons for PEP failure have included delays in PEP initiation,15,16poor adherence to PEP16,17 and already established HIV infection at the time of PEP initiation.18
The rare cases of PEP failure following occupational exposures were mostly reported over two decades ago.11,19-21 Occupational PEP failures have been described due to resistance mutations in the virus of the source22 and possible early primary HIV infection in an Australian healthcare worker who seroconverted after sustaining a needlestick injury from a viraemic, treatment-experienced source, despite commencing PEP only two hours later.23 Notably, despite completing the 28-day course, the healthcare worker had stopped PEP for four days in the third week.
- Completion of the 28-day PEP course has historically been low, ranging from 48% to 88%.24 However, less tolerable older PEP regimens, particularly those containing zidovudine,25,26 have in recent years been replaced by better-tolerated regimens, including the use of tenofovir disoproxil fumarate (TDF) as one component of the PEP backbone with an integrase inhibitor (versus a protease inhibitor) as a third drug, where required.25,27,28
Therefore, counselling on the importance of PEP adherence and seeking timely clinical review for PEP regimen modification if side-effects impact adherence remains a cornerstone of PEP management.