October 22, 2014
Last week, a scheduled interim analysis from the UK PROUD study found that daily oral pre-exposure prophylaxis (PrEP) with TDF/FTC (Truvada) to be “highly protective against HIV for gay men and other men who have sex with men in the UK.”
The announcement of these results was quickly followed by articles in the two UK newspapers: the Independent reporting that the study had “dramatically sped up” plans for the NHS approve PrEP, while the Daily Mail reporting that “NHS England have set up a group looking into the viability offering Truvada.”
The NHS is the world’s largest publicly funded health service providing free care for anyone who is a UK resident. The next step for TDF/FTC as PrEP would be “adoption” by the NHS, which would make this strategy available to all UK residents via programs subsidized and staffed by the UK government health service. This adoption process has no equivalent in the US or elsewhere, including Africa, where multiple different agencies advise, control and fund healthcare. For example, in the United States, the Food and Drug Administration approved a prevention indication for TDF/FTC and the Centers for Disease Control and Prevention has recommended it, but availability is via private insurance, Medicaid and demonstration projects.
Now both countries could be at the forefront of delivering PrEP through very different health systems.
The possibility for this PrEP strategy in the UK is a welcome advance, especially to those following the PrEP discussion in Europe. Until now European governments and agencies have been slow to consider PrEP. Earlier this year, two days after their sister agency in US issued guidelines on PrEP use, and a few months before that the WHO endorsed PrEP for MSM and discordant couples, the European Centre for Disease Prevention and Control (ECDC) issued a brief cautionary comment on PrEP. The WHO strongly recommended men who have sex with men be offered tenofovir-based oral PrEP. The ECDC comment in contrast vacillated, articulating questions about cost and concerns about side effects, potential for drug resistance and condom migration that experience and research have shown so far to be of manageable or minimal impact.
For those interested in seeing whether PrEP might work in Europe, the ECDC guidance was interpreted as European ambivalence or hostility toward PrEP. The ECDC statement was the first normative guidance since the 2012 European Medicines Agency (EMA) guidance, and one could be forgiven for thinking that Europe would be very, very late to PrEP, if they arrived at all.
Despite the tone of ECDC comment, the PROUD study could trigger real action. There is even some cause to believe that Europe could overtake the United States in PrEP implementation.
Europe needs PrEP. Europe has a major epidemic among gay men and other men who have sex with men. Recent data in Western and Central Europe shows that the number of HIV diagnoses among gay men and other men who have sex with men increased by 33% between 2004 and 2011.
But PrEP requires integration into primary care systems, and many European countries have good health system infrastructure. One of the key challenges of PrEP uptake in the United States is developing systems and educating providers to deliver PrEP. Several European countries have that infrastructure and payor systems integrated into those structures already.
Cost is the principal objection to PrEP, and Truvada’s patent is good only until 2021 in the US but 2018 in Europe. So this PrEP strategy could go to generic pricing in Europe three years earlier than the US.
European advocates are organizing. Early advocacy is already happening in France, Germany and the United Kingdom. At the Melbourne AIDS conference in July, advocates from Belgium, France, Italy, Germany, Greece, Netherlands, Portugal, Spain and United Kingdom met to discuss the state of PrEP implementation in their countries. There, the consensus was that not much was happening on PrEP in Europe. But now, things may start to change.
Europe wasn’t involved in the early PrEP efficacy trials, but the interim results from the PROUD open label study validated the protective effect of a daily oral PrEP strategy provided in the context of comprehensive HIV prevention. At the same time, the recent news from PROUD raises questions about the future of IPERGAY, an ongoing placebo-controlled trial that is designed to test if oral TDF/FTC for PrEP taken on an intermittent or ‘on demand’ basis (as compared to daily use in the other studies) reduced risk of infection among gay men and other MSM. The trial is currently ongoing in France and Canada and may also expand to Germany.
Advocates on both sides of the Atlantic have questioned the use of a placebo arm in IPERGAY since the FDA approved daily Truvada for prevention last July. As French and other European regulators, however, have yet to approve the use of Truvada as PrEP, therefore it is not currently available for prevention, only treatment. In a recent discussion of the PROUD results, IPERGAY investigators indicated that the trials independent data review board would be communicating with the analogous body for the PROUD study to share confidential information about the trial data. This step could lead to changes in the IPERGAY protocol.
Efficacy data are one piece of the PrEP puzzle. Acceptability and perceived benefits are also key—though harder to measure. Here, too, the data from daily PrEP are promising. At the Melbourne Conference, Kimberly Koester presented on people’s experiences taking PrEP in the iPrEx OLE study. The most striking finding was not the absence of condom migration. It was that fear before, after and during sex was a part of these men’s lives:
“So, in general, the anxiety, the HIV anxiety, is gone. I won’t say it’s gone-gone. But it’s not in the front of my head as it used to be, where I was obsessively worried about it while sex was happening.”
Losing that fear is a message that will resonate in Europe, and sooner than we think.