Pre-exposure prophylaxis for HIV in Europe

The use of pre-exposure prophylaxis (PrEP) as an HIV prevention strategy, particularly among men who have sex with men (MSM) as well as other population groups at higher risk of HIV infection, has been receiving more and more attention during 2014. Preliminary results of clinical trials and research studies suggest that it could be an effective HIV prevention tool for Europe.

As described in the ECDC report Evaluating HIV treatment as prevention in the European context (page 34), PrEP is an antiretroviral therapy-based HIV prevention strategy to prevent or at least reduce the risk of HIV infection in adults who have not been infected with the virus but are at high risk of infection. The treatment includes the daily use of specific oral antiretrovirals to prevent the virus from establishing a permanent infection.

The recently published final results of the extension of a large clinical study  (iPrEX OLE) conducted among MSM and transgender women showed that good adherence to PrEP was associated with a risk reduction of 84% for HIV infection (Grant RM, Lancet Infect Dis 2014;14: 820–29). The final results of the PARTNER study (Baeten JM, Lancet Infect Dis 2014; 14: 1055–64) among sero-discordant couples, indicated that once-daily oral treatment regimensprovides high protection against HIV-1 acquisition in heterosexual men and women (85% and 93% respectively).

On 16 October 2014 the UK Medical Research Council and Public Health England announced the interruption of the placebo arm of the ongoing PROUD clinical trial in the UK in the light of the results of an interim analysis of this trial, which indicated that PrEP is highly protective against HIV among gay men and other men who have sex with men at high risk of infection.

Similarly, on 29 October, the Recherche Nord & Sud Sida-HIV et Hépatites (ANRS) on the IPERGAY trial which is currently on-going in France and Canada to test an innovative, intermittent (“on-demand”) PrEP regimen among MSM, showed a very significant reduction of HIV incidence in the treatment group in its interim analysis. As a result, the placebo group in this trial was discontinued as well.

The interim findings of these two on-going clinical studies are expected to be published in early 2015.

These results contribute to growing evidence that PrEP should be considered as an additional prevention option for HIV infection. WHO has included a new recommendation on the use of PrEP in MSM as an additional prevention choice within a comprehensive HIV prevention package, in the consolidated guidelines for HIV prevention, released in July 2014.In the US, where Truvada®1 use for HIV prevention had been approved in 2012, PrEP is included as a recommended prevention measure in the Centers for Disease Control and Prevention clinical guidelines, published in May 2014. Based on available scientific evidence, these guidelines expand the target population for PrEP beyond MSM, to include heterosexually-active men and women at high risk of infection, people who inject drugs and HIV negative individuals whose partners are HIV positive.

ECDC comment on PrEP in EuropeThere is currently no agreed strategy on PrEP across the EU. In addition, the medication (Truvada®) is currently only approved in the EU for routine antiretroviral therapy (ART) use after HIV infection, and is only available for PrEP in the context of clinical research studies.

The outcome of the interim analysis of the two EU-based studies PROUD and IPERGAY are promising and these results may support the eventual inclusion of pre-exposure prophylaxis in the ‘HIV prevention toolbox’ in Europe, alongside existing measures. The British HIV Association/British Association for Sexual Health and HIV has indicated that, in the light of the findings from the PROUD and IPERGAY studies, it is “working with National Health Services England to devise a policy to consider the future availability of pre-exposure prophylaxis, alongside existing measures”, and may thus  revise the position statement that it issued in 2012 on the use of PrEP in the UK.

• PrEP is, however, not a ‘silver bullet’.  A critical issue regarding the effectiveness of PrEP is its dependence on adherence, as studies such as PARTNER and iPrEx have confirmed. Adherence has been shown to be of particular concern in women-centered trials (FEM-PrEP trial and VOICE), where lack of efficacy of PrEP was attributed to extremely low adherence as assessed by biometric analysis. How to achieve and maintain high levels of adherence to treatment remains a key implementation issue.A number of additional scientific and practical questions are still unanswered regarding PrEP. For example, the cost-effectiveness of PrEP in the long term requires further investigation, even more so in the context of competing health priorities. The novel approach tested in the IPERGAY study of PrEP “on demand”, if proven successful, may offer the prospect of reducing costs and lowering the need for high adherence.

In addition, the potential side effects for individuals receiving ART even though they are not HIV positive, as well as the potential risk of developing drug-resistance, if breakthrough infection occurs, must also be considered. What is more, the potential negative impact of PrEP on desirable levels of condom use and safer sexual behavior has to be carefully monitored in a non-trial environment. Finally, from an implementation perspective, increased testing frequency and adequate follow up of people on PrEP needs to be considered.Accumulating evidence on the effectiveness of PrEP indicates that more serious consideration needs to be given to its inclusion in the ‘HIV prevention toolbox’ in Europe, at least for MSM. This could be of particular importance in the EU/EEA area where the HIV epidemic is mainly a sexually transmitted disease, largely concentrated among MSM, and newly diagnosed infections in this group have increased by more than 30% during the past decade.

However, evaluation of the implementation in the ‘real world’, formal licensure (Truvada® is currently not approved for PrEP in the EU) and guidelines for use are still lacking in most EU countries. This makes it difficult to provide a clear recommendation at present that would apply across the entire European Union. ECDC will continue to follow closely the on-going research studies  on this prevention strategy, and looks forward to the full results of the PROUD and IPERGAY clinical studies when available in 2015. In close collaboration with our collaborative agencies, the Member States and the European Commission, ECDC will assess how best to integrate the new evidence in the current European prevention framework, in consideration also of the need to carefully understand the impact of any PrEP strategy on condom use, risky sexual behavior in the medium to longer term, as well as its cost implications, among other issues.

Footnotes

1 - Either tenofovir disoproxil fumarate (TNF) or emtricitabine plus tenofovir disoproxil fumarate (Truvada®)