Appendix A: Evidence for three-drug versus two-drug PEP regimens
There is no direct or compelling indirect evidence to support the greater efficacy of three-over two-drug regimens; rather, it has been extrapolated from evidence that a higher number of drugs or combination of drug classes have historically achieved better treatment outcomes for HIV. In previous years, three-drug combinations were recommended for the treatment of HIV. However, more recently, dual HIV therapy including an integrase strand transfer inhibitor (INSTI), or a non-nucleoside reverse transcriptase inhibitor (NNRTI) has shown non-inferiority to previously recommended three-drug regimens.88,89
A systematic review and meta-analysis of animal PEP studies found no difference in efficacy between single-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) or INSTI PEP, dual NRTI PEP or triple NRTI and protease inhibitor (PI) PEP, although several of the included studies were not powered to detect a difference.77
For neonatal PEP, a large randomised controlled trial found similar reductions in intrapartum HIV transmission for two drugs (zidovudine + nevirapine) and three drugs (zidovudine, lamivudine and nelfinavir), although both multi-drug regimens further reduced intrapartum HIV transmission by 50% over zidovudine given alone.12
Appendix B: HIV and body fluids
| Infectious | Potentially infectious | Non-infectious* |
|---|---|---|
| Blood Semen Pre-seminal fluid (pre-cum) Vaginal secretions Anal secretions Breastmilk Other body fluids contaminated with visible blood | Cerebrospinal fluid Synovial fluid Pleural fluid Peritoneal fluid Pericardial fluid Amniotic fluid | Faeces Urine Saliva Sputum Nasal secretions Gastric secretions Vomit Sweat Tears |
Legend
*Unless visibly contaminated with blood
Appendix C: Cost of PEP regimens
Table 6:Cost of PEP regimensa
| Regimen | Approximate cost / 28-day course (AUD $) |
|---|---|
| Tenofovir disoproxil (TD)/emtricitabine (FTC) | 40 |
| Tenofovir alafenamide (TAF)/FTC | 700 |
| Dolutegravir (DTG) | 625 |
| Raltegravir (RTG) | 442 |
| TD/FTC plus DTG | 665 |
| TD/FTC plus RTG | 482 |
| TAF/FTC plus DTG | 1325 |
| TAF/FTC plus RTG | 1142 |
Legend
* costs correct as at 20 Jan 2025
Further information about pricing is available from the Pharmaceutical Benefits Scheme (PBS).
For more information on drug dosing and adverse events, please see Adverse Effects of ARV Agents – HIV ARV Guidelines
Appendix D: Methods
A multidisciplinary Expert Reference Group (see Acknowledgements) was convened by ASHM in March 2022. The updated guideline is based on a comprehensive literature review conducted by a trained librarian from an Expert Reference Group member’s Institution (Walter McGrath Library, St Vincent’s Hospital, Sydney).
The search included dates from January 2015 to January 2022 and for literature in English. Databases searched were: the Cochrane Library, EMBASE (Ovid) and Medline 1996 – (Ovid). Public search engines such as Google were used to locate documents on the management of HIV exposures nationally and internationally. Keywords searched were ‘post-exposure prophylaxis’ or ‘post exposure prophylaxis’ or ‘PEP’ or ‘nPEP’ or ‘oPEP’ or ‘occupational exposure and HIV’ or ‘nonoccupational exposure and HIV’.
The formal review process was further informed by searches of the reference lists from publications of interest; grey literature and citations were also reviewed. The grey literature included: conference presentations, project reports, government reports, policies and strategies, and healthcare organisation publications. PEP guidelines and reference lists from the UK (2021),90 the US Centers for Disease Control (2016),91 and the World Health Organisation (2014)92 were also reviewed.
Final recommendations were developed following meetings and regular email correspondence between Expert Reference Group members on original drafts, comments and recommendations. David Templeton drafted the, Introduction, Background: evidence supporting the efficacy of PEP in preventing HIV acquisition, Evidence for two-drug versus three-drug PEP regimens, Antiretroviral agents not generally recommended for PEP, Side-effects of recommended PEP medications, Drug-drug interactions with PEP medications, Management of possible exposure to other conditions: Pregnancy and lactation and Adult sexual assault (>16 years of age). Charlie McLeod, Brendan McMullan and David Templeton drafted Additional Clinical Management Issues: Children younger than 16 years of age. Anna Pierce drafted Management of possible exposure to other conditions: Hepatitis B and Hepatitis C. Caroline Thng drafted Specific clinical situations for PEP: People who re-present for PEP after completion of a PEP course, People who re-present with additional high-risk exposure(s) while taking a PEP course and People who are on PrEP. Charlotte Bell drafted Clinical assessment and Specific clinical situations for PEP: People at negligible risk of HIV transmission who request PEP. David Lee drafted Management of possible exposure to other conditions: Sexually transmissible infections. Donna Tilley drafted Laboratory testing for HIV PEP recipients, Prescribing PEP, Specific clinical situations for PEP: People at risk of HIV acquisition who decline PEP and People who are transitioning from PEP to PrEP. John McAllister drafted Assessment of the risk of HIV transmission and When to Prescribe PEP. Louise Owen, Sarah Martin and Anna Pierce drafted Important note for general practitioners who have not previously prescribed HIV PEP. David Templeton was responsible for checking the accuracy of supporting references and writing the final version of the revised guideline.
In late 2024, after feedback from clinicians, a small working group (Dr Anna Pierce, Dr Louise Owen and Jude Armishaw, nurse practitioner) was convened by ASHM to streamline sections of guidance as part of a minor update to the Third Edition (2023) to improve clinical accuracy and usability which led to the Fourth Edition (2025) and the development of the HIV PEP Decision Making Tool.
Acknowledgement of Country