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School of Population Medicine
University of New South Wales
Senior Staff Specialist
South Eastern Sydney Local Health Network
Prof. Don Smith has disclosed that he has received funds for research support from ViiV and consulting fees from Gilead Sciences, Janssen, and ViiV.
Pre-exposure prophylaxis (PrEP) is an effective prevention strategy for individuals at high risk of acquiring HIV, as demonstrated in randomized clinical trials. The EPIC-NSW study sought to assess real-world implementation and effectiveness of coformulated emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) as PrEP in at-risk communities of gay and bisexual persons living in New South Wales (NSW), a large metropolitan area in Australia. In this commentary, I review the major findings of EPIC-NSW and highlight how these data can inform the next steps in PrEP strategies and populationwide HIV prevention efforts.
EPIC-NSW Study Design
The prospective, observational, open-label, single-arm EPIC-NSW study was a collaborative program involving academic, clinical, and government institutions, as well as the community. It required all stakeholders to reach a consensus on trial design. For example, community organizations wanted PrEP medicines available instantly with minimal barriers to access, whereas providers wanted to know that it would fit in with their clinical practice and would not promote baseline resistance to the drugs among persons who seroconverted (because FTC/TDF is an important backbone of first-line therapy for HIV).
The initial enrollment target was 3700 persons, but in response to high demand among eligible participants, the trial was expanded to 9596 at more than 30 sites. Once enrolled, participants received coformulated FTC/TDF for daily use and were followed for up to 24 months with routine testing for HIV and other sexually transmitted diseases, biannual renal function testing, and annual HCV screening.
During the course of 18,628 person-years of follow-up, 30 HIV infections were detected, corresponding to an incidence of 1.61 per 1000 person-years. This incidence was lower than what would have been expected, suggesting that widespread adoption of daily oral FTC/TDF can lead to lower rates of new HIV infections among a community of high-risk individuals. This outcome provided overwhelming evidence of demand and uptake of PrEP in this community as well as the ability of the health system to implement PrEP into standard practice. Moreover, the study highlighted the power of partnering among government, clinical, and academic institutions to achieve positive health outcomes.
Of importance, these data contributed to the Australian government’s decision to make PrEP available fully subsidized to persons at high-risk of acquiring HIV.
When we looked at the 30 people who seroconverted during the study, none was receiving PrEP at the time of their seroconversions; they had all interrupted it for a range of reasons. This highlights the need to keep reinforcing the support systems for those receiving PrEP, rather than assuming that it will be successful because it was proven efficacious in randomized clinical trials.
Although there was tremendous interest among community members to join the study initially, the data showed that only approximately two thirds of participants remained on PrEP at the end of the study. Why? There were several reasons.
Life circumstances can change over 2 years, and some participants had settled into monogamous relationships and no longer perceived themselves as high risk. Others moved out of state. In some cases, PrEP was discontinued due to renal toxicity, which can occur with long-term TDF use.
More generally, in this cohort of mostly young, healthy men with no underlying health conditions, I suspect it became burdensome for some to take a pill every day and to be told you must now interface with the healthcare system every 3 months for testing and medication dispensation.
Next Steps for PrEP
The idea that taking a daily pill for prevention can be burdensome for otherwise healthy individuals begs the question of how we can improve PrEP strategies in the future. I think we need long-acting modalities, similar to what we have seen for contraception. It should be more convenient and not require a visit to the clinic every 3 months. Persons with no other health conditions do not want to feel they are being medicalized and institutionalized into our services.
Ramifications for Population-Level HIV Prevention
What does EPIC-NSW teach us about population-level HIV prevention? First, I would recognize that enthusiasm—and consequently, effectiveness—is highest in the first year of rolling out free, widely available PrEP. Through a combination of highly engaged community members and providers strongly recommending PrEP to individuals who are at risk, there was a strong uptake of the intervention. However, the data demonstrate that some PrEP fatigue arose by the end of the study.
Second, I think HIV prevention efforts are most effective when widespread PrEP uptake is combined with a proactive treatment as prevention approach. Fortunately, in NSW, HIV treatment is fully funded by the federal government. There is no cost to individuals and no restriction on which treatments people are offered. Moreover, as EPIC-NSW was initiating, there was growing recognition that treating everyone who is HIV positive as soon as possible could help target community transmission. When free, widely available PrEP becomes available in an area, stakeholders should consider it an optimal time to try and eliminate HIV from their community through multiple strategies—as the initial enthusiasm is unlikely to be maintained long term.
Finally, the EPIC-NSW cohort primarily comprised individuals who were well engaged with their local community, which was predominantly inner-city populations of men who have sex with men. It was more challenging to engage with other individuals who were not well connected, including people who use injection drugs, sex workers, and people from non–English-speaking backgrounds or communities where their sexuality would be marginalized or where HIV was not acceptable. In Australia, we will need special efforts to better engage with these members of the community and promote more widespread PrEP use.
How do the lessons from EPIC-NSW influence your approach to PrEP? Answer the polling question and join the conversation by posting a comment.