Since the human immunodeficiency virus (HIV) was identified as the cause of acquired immune deficiency syndrome (AIDS) in the early 1980s, efforts to limit the spread of this virus have been global. The World Health Organization (WHO) has been instrumental in developing guidelines and facilitating all countries to implement measures to address this pandemic.
At the end of 2016, it was estimated that around 36.7 million people were living with HIV globally with 1.8 million new infections in that year alone. While HIV treatment options are becoming more affordable and effective, only 54% of adults living with HIV are currently receiving lifelong antiretroviral therapy (ART). While not a cure for HIV, ART can control the viral replication, allowing people with HIV to live long and productive lives.
Appropriate and timely initiation of ART can also help to prevent transmission. A 2011 trialinvolving 1,763 serodiscordant couples demonstrated a 96% relative reduction of HIV transmission when ART is initiated immediately compared to delaying initiation until the development of HIV-related symptoms or a decline in the CD4 count. However, this trial had a number of limitations which could restrict its application to the real world. The 2016 publication of the PARTNER study added further credence to this strategy known as ‘treatment as prevention.’ This study involved 1,166 serodiscordant couples in which the HIV-positive partner was taking ART, had a viral load of less than 200 copies/mL and engaged in condomless sex with their HIV-negative partner. The results demonstrated an overall transmission rate of zero over the 1,238 couple-years of follow-up. Evidence to support treatment as prevention is now considered extremely strong. People living with HIV who are able to maintain an undetectable viral load are now considered by some organisations to have effectively no risk of transmitting the virus to their HIV-negative sexual partners.
While HIV is estimated to be responsible for over 35 million deaths globally, Australia has largely been insulated from its devastating impact. Australia’s early response to the pandemic, including educational campaigns and targeted harm minimisation strategies, has resulted in a lower prevalence of HIV compared to many other countries. Equitable access to effective therapies has also helped, with 86% of people diagnosed with HIV receiving ART in 2016.
As part of Australia’s commitment to the United Nations Political Declaration on HIV, the ambitious goal was set to end new HIV infections in Australia by 2020. Significant advances have been made in some areas of transmission. For example, in the early 1990s, the transmission rate for babies born to HIV-positive mothers was 31.9%. This rate reduced to 1.5% in the five-year period of 2011-2015, with no mother-to-baby transmissions reported since 2013. However, the Australian Federation of AIDS Organisations (AFAO) reports that the total number of newly diagnosed HIV notifications has remained steady in Australia over the past few years.
Associate professor Guy, head of the Surveillance, Evaluation and Research Program at the Kirby Institute, believes that
“For HIV to decline nationally, we must focus on a combination of prevention strategies, including enhancing our testing and treatment efforts, making HIV self-testing available and ensuring equitable access to pre-exposure prophylaxis (PrEP) across Australia.”
From the 1st April 2018, PrEP is available on the Pharmaceutical Benefits Scheme (PBS). This medication comes in the form of a combination product containing tenofovir with emtricitabine. While PrEP has been available for some time, the PBS subsidy makes it more affordable which is likely to significantly increase its uptake among people at risk. To qualify for PBS-subsidised PrEP, adult patients must be HIV-negative and at medium to high risk of HIV infection as defined by the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) Guidelines.
Tenofovir with emtricitabine is not considered to be a complete treatment regimen for HIV infection. Therefore, PrEP should only be initiated in individuals confirmed to be HIV-negative within the seven days prior to starting treatment. If a patient had a high-risk exposure within the previous 72 hours, a course of post-exposure prophylaxis (PEP) may be required before starting PrEP. HIV status should then be tested routinely throughout therapy. If PrEP is initiated in an HIV-positive person or continued after contracting HIV, there is a risk of drug resistance developing.
The efficacy of PrEP is strongly correlated with patient adherence and the maintenance of detectable drug levels in the blood. Trials with high levels of adherence report a 95% or greater reduction in HIV incidence, while some trials with poor adherence have been stopped early due to a lack of efficacy. It is, therefore, vitally important for all patients considering PrEP to be counselled on how to take their medication effectively. For patients in a serodiscordant relationship, the importance of their partner’s compliance with prescribed ART should also be highlighted.
Daily PrEP doses should be taken with food to optimise tenofovir absorption. This medication has been well-tolerated during clinical trials with headache, nausea and flatulence among the more commonly reported adverse effects. These effects usually resolve within the first month of therapy and may be treated symptomatically. Renal injury and hepatotoxicity have also been reported, and PrEP is not recommended for people with an estimated creatinine clearance below 60mL/min. Discontinuation of PrEP can result in hepatitis B reactivation. Therefore, hepatitis B status should be tested prior to initiating therapy and vaccination offered if appropriate.
It is imperative that PrEP be used as part of a comprehensive approach to HIV prevention that includes other safer sex practices. The consistent and correct use of condoms should be encouraged to provide additional protection against HIV. Condoms are also important to prevent the spread of other sexually transmitted infections that can facilitate the transmission of HIV. Clinical trials suggest that PrEP is a highly effective means of preventing HIV transmission. It is hoped that the recent improved access to this therapy will take Australia one step closer to its goal of no new HIV infections.
It should be noted that PrEP differs from PEP (post-exposure prophylaxis). PEP is a four-week course of antiretroviral medications prescribed to individuals who are accidentally exposed to HIV. Exposures considered to be lower risk may use daily emtricitabine plus tenofovir or twice daily lamivudine plus zidovudine. Higher risk exposures may require the addition of twice-daily raltegravir or lopinavir plus ritonavir. To be effective in preventing transmission, these agents should be initiated within 72 hours of the exposure. In contrast, PrEP must be taken regularly.
- Antibiotic Expert Group. Prevention of Infection: Medical. In: eTG Complete. Melbourne: Therapeutic Guidelines; 2018.
- Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012; 367: 399-410.
- Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarassamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011; 365: 493-505.
- Heffron R, Ngure K, Odoyo J, Bulya N, Tindimwebwa E, Hong T, et al. Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa [version 2]. Gates Open Res. 2017; 1: 3.
- National Notifiable Diseases Surveillance System Working Group. Australia’s notifiable disease status, 2014: Annual report of the National Notifiable Diseases Surveillance System. Department of Health, 2016.
- Rodger AJ, Cambiano V, Bruun T, Vernazza P, Collins S, van Lunzen J, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA. 2016; 316(2): 171-81.
- Truvada® (tenofovir disoproxil fumarate and emtricitabine) Australian approved product information. Melbourne: Gilead Services. Approved May 2017.
- World Health Organization. HIV/AIDS. Geneva: WHO; 2017.
- Wright E, Grulich A, Boyd M, Comelisse V, Russell D, O’Donnell D, 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.