US regulators vote for approval of PrEP by large majority

Gus Cairns
Published: 11 May 2012

The US Food and Drug Administration (FDA) took a decisive step yesterday towards approving the use of the combination pill Truvada (tenofovir/FTC) as a prevention method for HIV-negative people.

The FDA’s Antiviral Drugs Advisory Committee (ADAC) voted by a majority of 19 to 3 in favour of recommending Truvada as PrEP (pre-exposure prophylaxis) for men who have sex with men, and by 19 to 2 with one abstention for an approval for use by the HIV-negative partner in serodiscordant couples.

There was a closer vote, however, when it came to recommending its use generally in individuals: 12 to 8, with two abstentions, voted for a general recommendation for any person at risk of HIV.

The ADAC decision was taken after an all-day meeting on 10 May. This meeting discussed the findings of a written report and also heard submissions from a large number of community prevention and treatment advocates. Interest was such that the FDA extended the time for submissions from advocates and community members from one hour to two and had to organise a ballot for access to the hearings.

The written report had concluded that concerns about safety and HIV drug resistance were not sufficient to delay the introduction of PrEP. It also decided that concerns about poor adherence levels seen in some randomised controlled trials, and about whether PrEP would negatively influence behaviour to such a degree that people ended up at greater risk of HIV, were beyond the remit of the FDA.

“I don’t think it’s our charge to judge whether people will take the medicine,” panellist Dr Tom Giordano told the Los Angeles Times. “Our charge is to judge whether it works when taken.”

Considerations of cost are also explicitly ruled out of the FDA’s remit when it comes to approving a new drug or indication.

The FDA is not bound to follow the recommendations of its advisory committees and will make a final decision by 15 June. However it is very rare for it not to do so and the large majority in favour of its approval for gay men and in serodiscordant couples makes this unlikely.

PrEP has always excited controversy amongst HIV prevention advocates and people affected by HIV. Some organisations have opposed its introduction and the AIDS Healthcare Foundation, in particular, has mounted a provocative campaign against its approval. “If you love Vioxx you’ll love PrEP,” read one poster displayed on bus shelters near the White House, referring to the painkilling drug that was withdrawn in 2004 when it was linked with heart attacks.

The majority of HIV prevention advocates, however, have supported PrEP. Mitchell Warren of the AIDS Vaccine Advocacy Coalition (AVAC) commented: "Some funders and policymakers have been awaiting a signal from the FDA before launching demonstration projects or developing implementation plans.

"The time for waiting is over. We need to get on with the work of setting priorities and rolling out PrEP to people who can benefit the most.”

The controversy was, if anything, reinforced when the randomised controlled trials (RCTs) of PrEP that have reported in the last 18 months – iPrEX, FEM-PrEP, Partners PrEP and TDF2 – produced strikingly different results, with headline efficacy levels ranging from zero (in FEM-PrEP) to 83% (for men in Partners PrEP). Studies of drug levels found that these results could be explained by different levels of adherence in trial participants. PrEP was 92% efficacious in participants in iPrEx who had detectable levels of drug in their blood, and it is clear that adherence levels will crucially determine whether it protects the people who take it. At present, RCTs have only tested daily dosing of PrEP, though a study in France, IPERGAY, is currently testing its efficacy in gay men when taken on a before-and-after-sex basis.

In contrast, concerns about negative behaviour change and participants putting themselves at greater risk of HIV have not been supported by RCT findings, but it is recognised that these will only be answered by an open-label study in which people know for sure that they are taking the drug and not placebo.

Such a study, called PROUD, has been suggested for the UK and is awaiting a decision on approval. In this study, gay men attending genitourinary medicine (GUM) clinics in the UK who are at significant risk of HIV will be offered Truvada PrEP plus a package of behavioural support and counselling, but will be randomised to receive the PrEP component either immediately or a year later.

Principal investigator of the proposed study, Dr Sheena McCormack of the UK Medical Research Council (MRC), told aidsmap: “It is unusual for the MRC to talk publicly about a trial before it receives approval, but in the case of PrEP it is so important that the trial involves and is supported by its target community.”