More questions from a European meeting

Shortly before the iPrEx results were announced, a community meeting was convened in Brussels by the European microbicides and biomedical prevention research consortium EUROPRISE, the European AIDS Treatment Group and the AIDS Vaccine Advocacy Coalition.¹

At this meeting, some more themes, recommendations and priorities emerged that were not all covered in the post-iPrEx discussions. Some were general issues that apply to trials of many different prevention methods.

For instance, the crucial importance of involving the community in which the trial takes place was emphasised – a factor that contributed to the success of iPrEx. ‘The community’ means members of all populations that might wish to participate in the trial or benefit from its results – not just HIV activists or policymakers.

The lack of arational, comprehensive prevention development programme in biomedical HIV prevention was noted. Such a programme would evaluate the contribution of different prevention technologies, select and move forward only the most promising candidates and, once methods were licensed, make rational decisions about which ones to fund and for whom.

There were, however, a couple of concerns that apply specifically to PrEP. One is about licensing requirements.Given the CAPRISA 004 and iPrEx results, would one more positive result of each concept be enough to ‘clinch the deal’ on licensing? It took three trials all reporting at least 50% efficacy for circumcision to be accepted as a valid prevention method. Will the same apply to microbicides and/or oral PrEP, or will higher efficacies be required? The two situations are rather different as any topical microbicide would have to go through a full drug-licensing procedure, whereas existing oral drugs only need a change of indication to include PrEP.

Another consideration was how active a role the ‘normative agencies’ (national and international organisations that issue guidelines, such as the US Centers for Disease Control and the World Health Organization) should take in issuing guidance on questions such as how often it is feasible to test people who are taking PrEP for HIV and whether to monitor for resistance.

A big gap, as mentioned above, is that so far PrEP and microbicide trials have either used continuous dosing or two doses before and after sex. But the way they are most likely to be used (discounting long-acting formulations) is if taken/applied as a single, ad hoc dose. Single-dose studies are planned, but there are no comparison studies that directly compare single- versus double-dose strategies and continuous- versus single-dose strategies.

The other big research gap is the more scientific one of finding correlates of protection. We do not know what tissue concentration in the genitals is protective, or how to time doses so that drug concentration peaks at the right time in order to prevent infection.