On 1 April 2018 TDF-FTC (brand name Truvada) became available on the PBS for HIV pre-exposure prophylaxis (PrEP). Previously only available in clinical trials or privately, PrEP can now be prescribed through the PBS by any GP.
The wider availability of this very effective prophylaxis has the potential to reduce HIV infection rates in Australia. This article examines what this new listing means for general practice, including when to consider PrEP, and what to take into account when prescribing.
- TDF-FTC as HIV PrEP is funded on the PBS.
- PrEP is extremely effective at preventing new HIV infections among patients with high PrEP medicine adherence.
- Correct assessment and counselling at baseline, followed by baseline and regular testing, are important for the effective use of PrEP.
ASHM – Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine
ELISA – enzyme-linked immunosorbent assay (HIV test)
HIV – human immunodeficiency virus
HPV – human papillomavirus
MSM – men who have sex with men
PBS – Pharmaceutical Benefits Scheme
PEP – post-exposure prophylaxis
PrEP – pre-exposure prophylaxis
RCT – randomised control trial
STI – sexually transmitted infection
TDF-FTC – tenofovir-emtricitabine (tenofovir disoproxil fumarate - 2',3'-dideoxy-5-fluoro-3'-thiacytidine)
TGA – Therapeutic Goods Administration
PrEP: New to the PBS
PrEP is the regular use of HIV medicines by people who are HIV-negative, but who are at substantial risk of contracting HIV, to prevent HIV infection. PrEP may be new on the PBS, but internationally it has a longer history. There have been extensive trials demonstrating its effectiveness in preventing HIV infection, and it has been in use for more than 5 years in the USA.1 Currently around 14,000 Australians at high risk of contracting HIV are receiving subsidised access to PrEP through trials conducted in most states, and others are accessing PrEP privately through personal importation.2
For Australians unable or ineligible to enrol in a study, PrEP has also been available on prescription, although the cost, around $1000 per month,3 has been prohibitive to many.
TDF-FTC (a nucleotide reverse transcriptase inhibitor [TDF] and nucleoside reverse transcriptase inhibitor [FTC]) has been available on the PBS as part of combination antiretroviral treatment for HIV.4 The new PBS listing improves accessibility of TDF-FTC for PrEP, by reducing the cost to the usual PBS copayment – $39.50 per month for general patients and $6.40 per month for concession card holders.5
Evidence for PrEP
The iPrEx study was a randomised, placebo controlled study (n = 2499) of HIV-seronegative men and transgender women who have sex with men. Participants received either TDF-FTC or a placebo pill once daily. The study found a 44% (95% CI 15 to 63, p = 0.005) reduction in risk of HIV infection in participants in the PrEP arm compared with the placebo arm. Although self-reported pill use was high, medicine exposure was measured objectively and showed that medicine adherence was substantially lower than indicated.
In the TDF-FTC arm, participants with a detectable study-medicine level had a relative reduction in risk of HIV infection of 92% (95% CI 40 to 99, p < 0.001) compared with those without a detectable study-medicine level.6 Post-hoc pharmacokinetic modelling analysis revealed that the relative risk reduction was 76% for 2 doses per week, and as high as 99% in participants with full adherence (7 doses per week).8
Participants in the study were counselled on the trial design involving a placebo and were aware that their pill might have no benefit. This may have contributed to the lower than expected pill use.
The UK PROUD study was an open-label randomised trial (n = 544) conducted in 13 sexual health clinics in England. Being open-label, it may give a better indication of the effect of PrEP in a real-world setting.6,7
Participants were randomly assigned to receive daily TDF-FTC immediately, or after a deferral period of one year. Three cases of HIV infection occurred in the group receiving PrEP compared with 20 cases in the deferred group (a relative reduction of 86% [90% CI 64 to 96, p = 0.0001]). The study authors concluded that these findings demonstrate the effectiveness of PrEP is not compromised in a real-world setting.7
Other studies have also demonstrated a reduced HIV infection risk using PrEP, compared with a placebo, in heterosexual and intravenous drug user populations.9-11 As in the iPrEx study, adherence to the PrEP medicines (as measured using blood plasma samples) was found to be important in reducing HIV infection.
Safety of PrEP
Clinical trials have shown that TDF-FTC for PrEP is associated with gastrointestinal adverse events including nausea and vomiting.12 One trial found that gastrointestinal adverse events occurred in 14% of participants using TDF-FTC compared with 5% for the placebo group.13 Most such events occur in the first month, however, and resolve with continued exposure.12
Although the long-term safety of TDF-FTC is not known, TDF is known to be associated with renal adverse events and loss of bone density.14
PrEP can be used in pregnancy.15 Among HIV-negative women at risk of HIV infection, pregnancy is a period of elevated risk of HIV infection. In addition, HIV infection acquired during pregnancy may be more likely to be transmitted to the infant than a pre-existing HIV infection,15 meaning that HIV protection is particularly important in this case for both mother and child.
Although experience with PrEP during breastfeeding is still lacking, there is substantial experience with breastfeeding while using TDF-FTC as part of antiretroviral therapy. Australian guidelines indicate PrEP may be continued during breastfeeding in women at substantial risk for HIV infection.15
TDF-FTC is not 100% effective in HIV prevention, particularly if medicine adherence is low. Furthermore, there are concerns that PrEP may lead to a deprioritising of other safe-sex precautions, increasing the risk of HIV infections as well as other STI infections for which PrEP offers no protection.14 The RCTs and observational studies on PrEP have shown some evidence of changes in risk behaviour (less condom use) and an increased incidence of STIs.12
Low adherence to PrEP could lead to an increased level of resistance to TDF-FDC, which forms the backbone of many antiretroviral HIV treatment regimens. Careful monitoring will be necessary to detect emerging new resistances.14
PrEP in clinical practice
Unlike prescribing to treat HIV, GPs do not need special certification to prescribe PrEP. However, with TDF-FTC now receiving PBS subsidy for PrEP, GPs are encouraged to take the e-learning course on prescribing PrEP for people at high risk of contracting HIV.
More information on PrEP can be found on the ASHM website and in ASHM’s decision-making tool for PrEP.
Key facts about PrEP
- The patient should be HIV-negative before starting PrEP, otherwise treatment-resistant HIV may develop.15
- Adherence to treatment is critical or HIV protection will be compromised.15
- PrEP offers no protection from other STIs, and so the continuing use of condoms is encouraged.16 Incidence of gonorrhoea and syphilis (for which condoms offer protection) has been increasing in Australia in recent years.17
Eligibility for PrEP
PrEP is PBS-subsidised for people at medium to high risk of contracting HIV.18 Guidelines to assess risk have been developed for MSM, injecting drug users, heterosexual people and gender-diverse people.15
People at high risk include gay and bisexual men and transgender people who have had unprotected anal sex with a man or who have been diagnosed with a rectal STI (gonorrhoea, chlamydia or syphilis). Heterosexual people with an HIV-positive partner who does not have an undetectable viral load and some people who inject drugs are also at high risk.15
In general, if a patient states that they may be at risk of contracting HIV, consider prescribing PrEP. Note that a patient may be at risk, but be unprepared or unable to explain this perceived risk.15
Discuss PrEP with your patient
GPs are well placed to determine which patients are at moderate to high risk of HIV infection and are thus eligible for PBS-subsidised PrEP. Practical tips for taking a sexual history include:16
- Routinely take a sexual history along with other components of the patient’s medical history. This indicates to the patient that you are open to discussing sexual health issues – many patients may fear that you are not.
- Keep in mind that the married man sitting in your consulting room may have other sexual partners and that these partners may be male.
- Use gender-neutral questions when asking about sexual partners, before clarifying the gender of these partners.
- Ask: ‘Do you have sex with men, women or both?’, rather than asking whether the patient is ‘gay’ or ‘homosexual’. The latter is a sexual identity, which is less relevant to HIV risk than the patient’s sexual practices.
Initiation on PrEP and follow-up: the key points
To ensure the HIV-negative status of a patient before initiation of PrEP, a fourth-generation HIV antigen/antibody combination ELISA test is required. The test will usually show results within a few weeks after exposure, and after 6 weeks, the test should detect approaching 100% of infections.16
If the patient has had unprotected sex within the last 72 hours
PrEP is not appropriate, and prompt initiation of PEP should be considered to reduce the risk of new HIV infection.15 Refer immediately to a PEP service if possible (found in tertiary hospitals, most regional hospitals and sexual health clinics). Referral is preferred as the PEP prescribed may differ depending on the risk of the exposure. If speedy referral is not possible, telephoning the PEP service for advice is recommended.
If the patient has had recent high-risk exposure
HIV test results may not be 100% reliable. Initiation on PrEP is recommended, with close HIV test monitoring for the next 2–8 weeks before reverting to standard PrEP monitoring.15
At the initial visit, screen for hepatitis B, hepatitis C, kidney function and STIs. Treat STIs as required, and consult an expert in the case of a positive hepatitis B or C test, or impaired kidney function. (PrEP can negatively impact kidney function.)15 Review and update immunisations for HPV, hepatitis A and B and meningococcus.20 Measure bone density if there are risk factors for low bone density, and actively monitor.15
Review the patient every 3 months. Review sexual practices and adherence to PrEP to reassess continuation of PrEP. Test kidney function and test for HIV and STIs.15
PrEP is the first biomedical prevention strategy that enables gay and bisexual men (including trans men) and trans women to effectively take charge of their own HIV risk.
With good adherence, PrEP is highly effective, and typical use of PrEP is more effective than typical use of condoms. This is not surprising when you consider that a PrEP pill can be taken in the morning with breakfast, at a time when people are usually clear-headed, whereas the effectiveness of condoms relies on a person using a condom during sex, a time when they may be intoxicated or otherwise excited, or just do not happen to have a condom at hand. In some cases, a person may be in a situation where they cannot exercise their right to use a condom.
Concerns have been raised that PrEP use will result in a reduction in condom use and an increase in STIs. Some risk compensation is likely to occur, but it’s important that we keep our eyes on the prize: San Francisco has seen a 50% drop in new HIV infections since PrEP was approved by the US Food and Drug Administration in 2012, and we now have the opportunity to achieve similar reductions in Australia.
PrEP also provides an incentive for patients to return for 3-monthly STI screens, as recommended by the Australian STI guidelines, which should help efforts to control STIs. At the same time, regular PrEP appointments provide an opportunity to screen for mental health difficulties and problems from the use of alcohol and drugs, and these problems disproportionately affect the same groups of people who may benefit from PrEP.
Another concern is that increased use of PrEP may result in more people acquiring antiretroviral-resistant strains of HIV, which would limit their HIV treatment options. This has been observed in PrEP trials, but mainly when people started PrEP when they were already HIV-positive. This highlights the importance of ensuring that people are HIV-negative when they start PrEP, and that they have 3-monthly HIV tests during PrEP use, to minimise their exposure to PrEP if they do acquire HIV.
Prescribers should also keep in mind that those without a Medicare card (eg, overseas students) can be assisted to access PrEP under the TGA’s personal importation scheme.
Dr Vincent Cornelisse
BSc(Hons) MBBS FRACGP FAChSHM
Sexual health physician, Melbourne, Victoria
- US Department of Health and Human Services/US Food and Drug Administration. Truvada for PrEP fact sheet: ensuring safe and proper use. Silver Spring: Food and Drug Administration, 2012 (accessed 14 March 2018).
- Australian Federation of AIDS Organisations. PrEP fact sheet. Newtown: AFAO, 2018 (accessed 9 March 2018).
- ACON. How much does PrEP cost? Sydney: ACON, 2016 (accessed 15 March 2018).
- Pharmaceutical Benefits Scheme. Tenofovir + emtricitabine. Canberra: Commonwealth of Australia, 2018 (accessed 8 March 2018).
- Pharmaceutical Benefits Scheme. Schedule of Pharmaceutical Benefits - summary of changes. Canberra: Pharmaceutical Benefits Scheme, 2018 (accessed 11 April 2018).
- Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587-99.
- McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 2016;387:53-60.
- Anderson PL, Glidden DV, Liu A, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med 2012;4:151ra25.
- Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2013;381:2083-90.
- Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012;367:399-410.
- Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012;367:423-34.
- Pharmaceutical Benefits Advisory Committee. Tenofovir with emtricitabine, tablet containing tenofovir disoproxil fumarate 300 mg with emtricitabine 200 mg, TRUVADA. Public Summary Document - July 2017 PBAC Meeting Canberra: Pharmaceutical Benefits Scheme, 2017 (accessed 22 March 2018).
- Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med 2015;373:2237-46.
- Pharmaceutical Benefits Advisory Committee. TRUVADA tablets, emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg, Gilead Sciences Pty Ltd. Public Summary Document - July 2016 PBAC Meeting Canberra: Pharmaceutical Benefits Scheme, 2016 (accessed 22 March 2018).
- Wright E, Grulich A, Roy K, et al. Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine HIV pre-exposure prophylaxis: clinical guidelines. J Virus Erad 2017;3:168-84.
- Cornelisse VJ, Fairley C, Roth NJ. Optimising healthcare for men who have sex with men: A role for general practitioners. Aust Fam Physician 2016;45:182-5.
- Kirby Institute. Australia’s annual report card on STIs and blood-borne viruses: Gonorrhoea and syphilis on the rise, HIV stable, and some good news on hepatitis. Sydney: Kirby Institute, 2017 (accessed 6 November 2017).
- Pharmaceutical Benefits Advisory Committee. December 2017 PBAC meeting – positive recommendations. Canberra: Pharmaceutical Benefits Scheme, 2017 (accessed 9 March 2018).
- Australasian Society for HIV Viral Hepatitis and Sexual Health Medicine. Taking a sexual history & contact tracing. Australian STI Management Guidelines for use in primary care Sydney: ASHM, 2016 (accessed April 2016).
- Better Health Victoria. Time to immunise - free vaccines for men who have sex with men. Melbourne: Department of Health & Human Services, State Government of Victoria, 2018 (accessed 14 March 2018).