Terminology
WHO defines pre-exposure prophylaxis (PrEP) as the use of oral tenofovir disoproxil fumarate (TDF) or co-formulated TDF/emtricitabine (TDF/FTC) or co-formulated TDF/lamivudine (TDF/3TC) by HIV-negative people to prevent HIV acquisition (FTC and 3TC are considered interchangeable). In 2019, the US Food and Drug Administration approved emtricitabine + tenofovir alafenamide (FTC/TAF or F/TAF, Descovy®) as another drug that can be used for PrEP.
PrEP can be taken on a daily basis (daily PrEP) or around the time of exposure as event-driven PrEP, also known as event-based PrEP (EB-PrEP) and on-demand PrEP.
The concept of PrEP and evidence of its efficacy
The concept of using antiretroviral drugs prior to, or around the time of, risk events and is similar to that for prevention of mother-to-child transmission of HIV infection [11], PEP [50] and the use chemoprophylaxis for the prevention of other infectious diseases (e.g., malaria [64].
TDF/FTC was originally selected for PrEP because of its pharmacologic and pharmacokinetic properties. According to prescribing information [65] it has potency against wild-type HIV, but low potential of selecting for TDF-resistant mutants, low likelihood of metabolic/mitochondrial toxicity, and a pharmacologic profile supporting daily use. Adverse reactions, particularly new onset or worsening of renal disease, are extremely rare. Evidence for the effectiveness of both daily and intermittent TDF/FTC PrEP regimens was first obtained from animal studies, including macaque models infected with SIV or simian-human immunodeficiency virus (SHIV). [66, 67]
International Pre-Exposure Prophylaxis initiative (iPrEx) was the first randomised clinical trial of PrEP efficacy, which enrolled 2,499 participants in six countries and reported that PrEP reduced HIV incidence by 44% (95%CI:15–63) and that detectable drug in the blood was strongly correlated with the prophylactic effect of up to 99% protection. [68] Since then, eighteen randomised clinical trials, open-label extension trials and demonstration studies investigated the efficacy of PrEP and reported that when used with optimal medication adherence, daily PrEP is a highly effective HIV prevention strategy for MSM, heterosexual men and women, transgender people, and people who inject drugs at-risk of HIV acquisition. [69] As is the case with ART, adherence is the key determinant of PrEP efficacy. [69] In addition, EB-PrEP was investigated in a limited number of studies, which showed high effectiveness and acceptability of this PREP schedule in MSM, including those who engaged in risk events infrequently. [70-72] The relative reduction in incidence of new HIV infection due to EB-PrEP was 86% (95% CI: 40% – 98%) in a double-blind randomised controlled trial (IPERGAY) conducted in France and Canada [70] and 97% (95% CI 81%–100%) in its open label extension. [71]
Very few cases of antiretroviral drug resistance were observed in people taking daily DTF/FTC for PrEP, and all of them were associated with very poor adherence to PrEP. [73] No effects on reproductive health outcomes were reported. Key safety issues associated with daily PrEP among participants in RCTs included: a start-up syndrome (nausea, vomiting and dizziness) experienced by 1-18% of trial participants, Grade 2-3 creatinine elevations in 0.2% of participants and 0.4% to1.5% loss of bone mineral density, which was not associated with fracture risk and returned towards baseline after stopping PrEP. [73]
For a full review of PrEP safety and efficacy please see the CDC “Pre-exposure prophylaxis for the prevention of HIV Infection in the United States– 2017 update” starting from page 16 of: https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf.
Co-formulated tenofovir and emtricitabine for use as PrEP by people at risk of HIV infection is now recommended as standard of care in clinical guidelines in the US, Europe and Australia [74], as well as globally through WHO guidelines. [75] Based on recent evidence [70-72], EB-PrEP has recently been recommended by the WHO as an option for MSM and by the updated PrEP guidelines in Australia. [76]
PrEP implementation
PrEP access
Expanded PrEP implementation in Australia started with two population-based implementation trials, EPIC-NSW in New South Wales [77, 78] and PrEPX in Victoria. [79, 80] Now, PrEP is a key pillar of the National HIV Strategy.
Antiretroviral drugs used as PrEP in Australia are now registered with the Therapeutic Goods Administration (TGA) for that indication [81] and they are subsidised by the Australian Pharmaceutical Benefits Scheme (PBS). [82] Generic co-formulated TDF/FTC for use as PrEP can also be legally imported into Australia for personal use and is currently cheaper than the cost of a PBS prescription ($39.50/30 days for non-concession card holders). Various websites offer access to PrEP via self-importation and some offer free access, for those unable to afford PrEP, via a coupon system e.g. PAN (PrEPaccessNOW) at: http://pan.org.au/assistance-scheme/ As with any on-line purchase, caution should be exercised. Reputable sites verified and recommended by AIDS organisations or established Australian PrEP providers should only be used for on-line purchase.
Access to PrEP is crucial to realising its benefits. General practitioners and nurses should be aware of people not currently benefiting from PrEP who might do so (younger men and people born overseas without access to Medicare – see Background to this chapter) and assess their barriers to, and options for, access.
PrEP uptake trends
By the end of December 2018, approximately 18,530 individuals were accessing Medicare-subsidised PrEP in Australia, approximately half of them were in NSW and 99.1% of all users were males. [83] However, at a time of increasing PrEP uptake, increases in condomless anal intercourse were recorded in gay communities in Sydney and Melbourne as well as increasing diagnoses of STIs, such as anal gonorrhoea and chlamydia and new syphilis diagnoses. [84] The latter can be partly attributed to increased STI testing in MSM using PrEP, though this trend was significant regardless of the frequency of testing. [80]
PrEP prescribing
According to the national PrEP guidelines, all general practitioners and other medical specialists can prescribe PrEP using a PBS streamlined authority arrangement. No specialist training is required to prescribe PrEP. Resources and training guidance are available for clinicians who are new to prescribing PrEP. [76]
The newly updated ASHM 2019 PrEP guidelines [76] recommend daily PrEP for all people at risk of HIV infection. In addition, they also recommend that on-demand PrEP should be offered as an alternative option to cis-gender MSM.
According to the current 8th National HIV strategy, which aims for fast PrEP uptake and broad coverage among people who are at medium or high risk of being infected with HIV [85], and the updated national PrEP guidelines [76], general practitioners and nurses will play an increasing role in the provision of PrEP. They will play a key role in assessing people for clinical and behavioural eligibility for PrEP; provide PrEP prescriptions and regular follow-up and support services. The goals of PrEP services are described in Table 6.
Table 6. Goals of PrEP services (from the national PrEP guidelines [76])
For many general practitioners and nurses new to PrEP, prescribing may be unfamiliar but is described in detail in the updated ASHM 2019 PrEP guidelines. [76] PrEP training and resources are also available on the ASHM website to assist clinicians.
Assessment of suitability for PrEP
When assessing people for PrEP eligibility and suitability, it is important for general practitioners and nurses to understand a shift in the national PrEP prescribing guidance, from targeted to broader access to PrEP. [76] Targeted PrEP prescribing (focused on high risk MSM) was the key feature of Australian PrEP implementation guidelines up to now, due to the limited PrEP availability prior to the PBS listing of PrEP. The goal of the current 8th National HIV strategy is fast PrEP uptake and broad coverage of people who are at medium or high risk of being infected with HIV. [85] Therefore, clinicians are now recommended to assess whether PrEP suits the needs of their patients, and that can be done by using assessment criteria listed in Table 7. The guidelines also include recommendations on how to discuss behavioural risk reduction strategies.
Table 7. PrEP suitability criteria for different population groups (from the National PrEP guidelines [76])
Note: for more detail on how to apply these criteria in practice, please see Chapters 4 and 14 of the guidelines.
Nurses’ roles in PrEP
PrEP use in Australia as part of an individual and population HIV risk reduction strategy is now wide-spread. Nurses have an important role to play (Table 8).
Table 8. The nurse’s role in pre-exposure prophylaxis
|
· Providing a nurse-led PrEP service · Ensuring that those at risk know about PrEP and current pathways to access in Australia · Referring onwards to providers who can facilitate PrEP access · Adherence education and support o The need for a high level of adherence to the regimen and dosing schedule o Choosing the optimum dosing time based on the client’s routine work and leisure patterns, including discussion around the dosing window – a rigid, fixed time to dose sets clients up to miss a dose and fail o Strategies to assist adherence – teaching cueing (the act of associating pill taking with a habitual behaviour), visual and electronic reminders, pill boxes, preparing for the unexpected: keeping a supply at work, in the car, in a bag, at a friend’s house, borrowing from a friend o What to do if a dose(s) is/are missed o For vulnerable groups, intensive support, case management, directly administered or observed therapy (DOT), partial-DOT, financial incentives. · Education about maintaining healthy bones · How to access help if unexpected side-effects occur o The nurse can provide the first port of call and access to help by encouraging re-presentation and providing telephone access and support |
Adherence to the PrEP dosing schedule is also crucial to realising its benefits. People who most need PrEP may well be those who most struggle to maintain high levels of adherence. They are often MSM, and others, who have problems with alcohol or drug use or significant mental health problems. Rather than exclude these vulnerable groups from PrEP access because of concerns about poor engagement and adherence, ways should be found to support the adherence required. In the IDU Bangkok PrEP study, participants received Truvada by directly observed therapy (DOT) 86% (SD 25%) of the time and were compensated for travel and the time required by the study procedures.[86]
Key components of medication adherence counselling are presented in Table 9.
Table 9. Key components of medication adherence counselling (from the national PrEP guidelines [76]).
Nurses can and ought to have a pivotal role in exploring and providing innovative methods of PrEP medication adherence support in marginalised, vulnerable populations, which could include DOT, other forms of highly supported therapy and the provision of financial incentives.
Models of PrEP services
The prescription and provision of PrEP is straightforward for many medical practitioners. However, those who are less experienced in serving populations at high risk of acquiring HIV infection and STIs (e.g. MSM, transgender and gender-diverse people, indigenous Australians, women involved in sex work, people whose partners are at high risk for HIV/STI, and people who inject drugs) may wish to consider establishing relationships with experienced and accredited HIV s100 prescribers, HIV clinics and sexual health centres, that can provide information and support if required and may be able to do so via Telehealth. Initiatives such as telementoring [87] and innovative Information and Communication Technology (ICT) solutions offered by eHealth NSW [88] are good examples of how communication technologies can support new PrEP prescribers in remote areas where traditional sexual health services may be limited.
When embarking on PrEP prescribing, consider the capacity of your practice to accommodate new patients and maintain their follow-up every 3 months. Several approaches may be helpful in dealing with these changes to practice:
- Careful planning of clinic appointments to allow sufficient space for PrEP initiation and regular follow-up visits
- Where resources allow, automating most steps in the patient pathway, to reduce the patient registration-to-PrEP prescription time
- Having clinical nurse specialists, or trained nurses with clinician supervision in charge of PrEP-related services where possible
- Developing systems and procedures for recording and monitoring PrEP use
- Developing a customised communications plan for PrEP demand creation