Terminology

Post-exposure prophylaxis (PEP) was one of the first strategies to employ antiretroviral drugs for the prevention of HIV infection. It involves a 28-day course of antiretroviral drugs initiated within 72 hours of a potential high-risk exposure to HIV. ^[37]

The concept of PEP and evidence of its efficacy 

Animal models showed that within 3-5 days after initial exposure, HIV replicates in the skin and mucosa before spreading through lymphatic vessels and developing into a systemic infection ^[38]. This delay in systemic spread leaves a “window of opportunity” for post‐exposure prophylaxis (PEP) using antiretroviral drugs designed to block replication of HIV.

The efficacy of PEP in preventing retroviral infection was first demonstrated in non-human primate models in the early 1990s. ^{[39, 40]} The use of occupational PEP has been recommended since zidovudine was first found to be associated with a significantly lower likelihood (by 81%) of HIV infection following percutaneous exposure among healthcare workers in a case-control study conducted in 1997. ^[41] For ethical reasons, PEP efficacy has never been evaluated in controlled studies in humans, but RCTs of PEP efficacy have been conducted in primate models, especially simian immunodeficiency virus (SIV) infection of macaques. ^[42] The use of PEP is also supported by results of the trials demonstrating the efficacy of antiretroviral drugs in preventing mother-to-child HIV transmission. ^[43] Over time, PEP indications have expanded to cover non-occupational exposure, including accidental exposure, consensual sex, and sexual assault.

Studies showed that HIV seroconversions are rare in MSM who complete the prescribed course of PEP. ^[44-46]; however, adherence to the 28-day schedule is important ^[47,48]

Non-occupational PEP has been in wide-spread use in Australia since 1999 and is recommended by the Australian Government’s Department of Health and Ageing.^[49] The Australian National PEP guidelines ^[50] recommend 28 days of ART with two or three drugs (at prescriber’s discretion) for an HIV transmission risk event of ≥ 1:15,000. Australian MSM and, to a lesser extent, people who inject drugs, are the principal target groups.

In recent years, there have been increases in PEP use among MSM, particularly in Australia ^[51], UK ^[52], and the USA ^[53], which could be attributed to improved knowledge and awareness of PEP, PrEP implementation and increased access to antiretroviral drugs for HIV prophylaxis. However, unlike TasP and PrEP, PEP has not achieved the same the levels of uptake and public health impact because of its inherent limitations: people who were exposed to HIV have to recognise the potential risk, and request and start PEP within 72 hours of exposure. ^[50]

PEP implementation

Any doctor or nurse working in HIV and sexual health, family planning, an emergency department or in general practice require a minimum of PEP literacy (see Table 3). Nurses in particular have diverse roles in the assessment and provision of PEP (see Table 4).

Table 3. Minimum post-exposure prophylaxis (PEP) literacy

Table 4: Nursing roles in non-occupational PEP

Most potential exposures to HIV occur outside business hours or over a weekend.  In 2017, 51% of HIV risk events prompting assessment for PEP at St Vincent’s Hospital, Sydney occurred on a Saturday or Sunday. Of the 170 (49%) that occurred during a week day, 10% were between the hours of 08:30 and 17:00; the usual operating hours of clinics that provide PEP. Thus, emergency departments assess the majority of presentation for PEP and nurses who work in emergency departments are a particular group who need to be PEP literate.

In addition to a minimum PEP skill set, nurses provided with adequate training, support and resources are also capable of independently assessing and managing patients requiring antiretroviral drugs as PEP.

The National PEP Guidelines provide comprehensive information about risk assessment. In brief:

• An HIV risk event needs to have occurred
• The person with whom the event occurred needs to be HIV positive or from a population likely to have HIV infection
• The patient needs to present for assessment within 72 hours of the event

Table 5 presents a simple flow-chart that can be used as a PEP risk assessment tool.

Table 5. Risk assessment for non-occupational PEP

For a comprehensive guide to risk assessment, see the Australian National PEP guidelines available at: http://www.ashm.org.au/pep-guidelines/

PEP does not always prevent HIV acquisition. The time to first PEP dose, incomplete PEP adherence, continued HIV risk behaviour and primary antiretroviral drug resistance have each been linked to PEP failure.^[54] [55]

Time to first dose

PEP appears to be most effective when administered as soon as possible after exposure. In macaques, tenofovir initiated within 24 hours of a SIV challenge provided 100% protection from infection vs 50% and 25% when initiated at 48 and 72 hours, respectively.^[56]  In seven human cases of seroconversion following PEP, the median time from exposure to first dose of PEP medication was 45.5 hours (range 14-72.4 hours) and three of the seroconversions to HIV in this series initiated NPEP after 48 hours post exposure, although this difference was not statistically significant.^[57]. Health practitioners should be aware of the critical nature of time with regards to PEP, educate accordingly, facilitate rapid referral if required and, in emergency departments, allocate a high triage priority to patients who present for PEP.

Incomplete adherence

Intolerable side-effects of antiretroviral drugs result in many people failing to complete the prescribed course of PEP. In a meta-analysis of PEP adherence, completion rates were 57% overall and 67% in MSM.^[58] Toxicity-driven discontinuation was commoner with three-drug regimens than with two-drug regimens (2% vs 9% respectively).^[17] The World Health Organization (WHO) recommends that three antiretroviral drugs be universally used.^[18].

Given that between one half and one third of people do not complete the prescribed course of PEP, principally because of side-effects, the choice of safe, tolerable drugs for use in PEP is paramount and health practitioners have an important role in supporting people on PEP who experience side-effects (see Table 3). In Australia, Truvada (emtricitabine and tenofovir disoproxil fumarate) with the integrase inhibitor raltegravir is widely used as a three-drug NPEP. In MSM, it has been shown to be well tolerated with high rates of on-drug adherence, treatment completion and, where a protease inhibitor is the third drug, a low risk of potentially dangerous drug reactions.^[59] More recently, Truvada with the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine and Truvada with the integrase inhibitor dolutegravir have both been evaluated as three-drug PEP in MSM; both have also demonstrated low toxicity, high adherence, high completion rates and the added convenience of once-daily dosing.^[60] [61]

Continued risk of HIV acquisition and use of PEP

PEP use is a good indicator of future HIV risk and acquisition. Australian MSM who have ever used PEP are around three times more likely to eventually acquire HIV infection when compared to men who had never used PEP.^[62] This heightened risk is less about drug failure and more about inability to modify risk behaviour or, indeed, a negative past experience while on PEP.  The importance of carefully evaluating and choosing the best agents to use as PEP has been discussed. By employing a variety of behavioural interventions, sexual risk (as measured by condomless anal sex) in MSM can be reduced, at least in the short term, by about third.^[63]  So referral to appropriate services of MSM interested in addressing risk behaviour remains important in the new era of PEP. PEP initiation after a risk event is usually a stressful time and clients often reflect on their risk behaviours, thus presenting an opportunity for brief intervention and referral. While behavioural interventions in MSM interested in change are effective, referral of MSM uninterested or ambivalent about change in behaviour is not. Lecturing and scare tactics are equally unproductive. In 2017, 79 (22%) of 358 people had > 1 episode of PEP through the Sydney St Vincent’s PEP service.  Re-presentation for PEP is a new opportunity to keep an HIV-negative person HIV negative and to explore and address the context of the risk. Health practitioners have an important role in providing a positive, non-judgmental and enabling environment. ‘I’m really glad you’ve presented for assessment’, ‘I’m really pleased you’ve started (re-started) PEP’ are positive and affirming ways to start a client PEP encounter. An HIV-negative MSM who has difficulty consistently using condoms and is deterred from using PEP because of health-care provider attitude or censure may become an HIV-positive MSM.

NPEP has been the predominant use of antiretroviral drugs to prevent HIV infection in HIV-negative Australian MSM and others at high risk of infection; however, pre-exposure prophylaxis (PrEP) (see below) has the potential to change this situation. PEP will still, however, have a place as:

• A gateway to PrEP
• An adjunct to PrEP in the context of poor adherence and a high-risk HIV event
• An option for MSM who are not at high or imminent risk of HIV acquisition but who still have intermittent risk events and have not started PrEP
• A risk reduction strategy for MSM who choose not to use PrEP