Table 2 details when PEP is indicated and which regimen to use (two-drug versus three-drug) for potential sexual and non-sexual exposures to HIV.

A comprehensive risk assessment should inform the decision to initiate PEP and be made on a case-by-case basis.

Situations with greater uncertainty or complexity (including known or suspected antiretroviral resistance in the source, pregnancy, lactation, or a history of renal impairment or chronic HBV in the patient presenting for PEP) should be discussed as soon as possible with a specialist (e.g. Sexual Health, Infectious Diseases, Immunology, experienced s100 prescriber general practitioner, experienced Nurse Practitioner), but should not delay initiation of PEP. 

Robust evidence has proven that HIV is untransmittable by sexual activity when the source is on treatment and has an undetectable viral load,^30-32 now referred to in global health promotion programs as ‘undetectable = untransmittable’ or U=U^33,34 However, source information is often unavailable in PEP decision-making. If doubt exists, PEP should be initiated as outlined in Table 2 under: Source known HIV positive. HIV VL unknown or detectable.

In the occupational setting, an exposure means contact with potentially infectious bodily fluids or tissue that poses a risk of HIV transmission via: 

1. percutaneous injury: needlestick or sharps injury contaminated with source’s blood or body fluids
2. mucous membrane: splash injury to the eye or non-intact skin 
3. deep or multiple bites if source likely to be HIV positive and visible blood in source’s mouth

Body fluids thought to be able to transmit HIV are:³⁵

• blood
• semen
• pre-seminal fluid (pre-cum)
• vaginal secretions
• anal secretions
• breastmilk 
• other body fluids contaminated with visible blood.

Body fluids that may also potentially be infectious are:³⁵

• cerebrospinal fluid
• synovial fluid
• pleural fluid
• peritoneal fluid
• pericardial fluid
• amniotic fluid.

Body fluids not considered infectious unless visibly contaminated with blood:³⁵

• faeces
• nasal secretions
• saliva
• gastric secretions
• sputum
• sweat
• tears
• urine 
• vomit.

There are few data to support U=U in the occupational setting or for people who inject drugs after sharing needles and injecting paraphernalia. Therefore, this guideline continues to support recommending or considering PEP for occupational and other sharps exposures where indicated, as outlined in Table 2.

There is no individual or population-level evidence to inform the threshold at which PEP is indicated. In this 3rd edition, we have included four categories that were informed by the available evidence base: 

1. Recommend three-drug PEP: the benefits of three-drug PEP are considered to outweigh the risks, and three-drug PEP should be prescribed unless contraindications exist
2. Recommend two-drug PEP: the benefits of two-drug PEP are considered to outweigh the risks, and two-drug PEP should be prescribed unless contraindications exist
3. Consider two-drug PEP: the benefits of PEP are less clear and should be balanced against the risks, including consideration of co-factors (outlined in footnotes of Table 2), which may increase risk of HIV acquisition
4. PEP not recommended: the risk of HIV transmission is considered negligible, and PEP should not be prescribed.