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Today the leaders of the PROUD study of daily oral TDF/FTC (brand-name Truvada) for PrEP among gay men and other MSM in the UK announced that the trial protocol would change due to early evidence of effectiveness. The study’s official statement said, in part, “Interim analysis of the PROUD study data has shown that pre-exposure prophylaxis is highly protective against HIV for gay men and other men who have sex with men (MSM) at high risk of infection. On this basis, the PROUD Steering Committee has announced that participants currently on the deferred arm of the study, who have not yet started PrEP, will be offered the opportunity to begin PrEP ahead of schedule.”
The specific data on rates of HIV infections, PrEP adherence and risk behaviors that guided this decision were not made available. However, based on what has been released, it is clear that this is welcome news that confirms, once again, that this PrEP strategy works when it is taken correctly and consistently. It is also clear that rates of HIV infections among PROUD participants were higher than the study had originally anticipated. The number the team had anticipated at this stage in the trial would not have been sufficient to generate a conclusion about effectiveness. The study is thus also a grave reminder that comprehensive health care, including HIV prevention and treatment still isn’t reaching all gay men and transwomen who need it.
PROUD’s original design called for a two-phase investigation: A 500-person pilot study, scaling up to a 5000-person trial. In the pilot, which launched in 2012, half the participants were randomly assigned to receive daily oral PrEP immediately, along with a comprehensive prevention package including access to post-exposure prophylaxis (PEP). The other half were assigned to a deferred arm that would receive the comprehensive prevention package for 12 months and then be offered the opportunity to initiate the PrEP strategy. This two-arm design also would have been used in the expanded, second phase of the study.
This announcement came after a scheduled review of the data by the trial’s independent review body (the Independent Data Monitoring Committee, or IDMC). As a next step, the PROUD team has developed and submitted a protocol amendment that would allow all of the participants, including those in the deferred arm, to receive PrEP. They have also begun the process of calling participants back to inform them about the trial data. Right now, the UK National Health Service does not cover TDF/FTC for PrEP. Once the protocol amendment is approved, all PROUD participants will have access to PrEP. Additional steps, including analysis of all the data, will lead to NHS consideration of PrEP as public health tool.
One key question is: What does the development with PROUD mean for IPERGAY, a study of an intermittent PrEP strategy using TDF/FTC (that is also enrolling gay men and other MSM? IPERGAY is placebo-controlled, meaning that participants do not know whether they are receiving the active drug or an inactive pill. IPERGAY has been under some degree of scrutiny for its placebo-controlled design since it launched after the iPrEx trial which found efficacy among gay men, MSM and transgender women with once-daily dosing. The trial team has defended the design, in part by pointing out that IPERGAY was testing a different dosing strategy. With additional evidence of efficacy from PROUD, this placebo-controlled design needs to be re-examined once again. IPERGAY investigators have indicated that the PROUD and IPERGAY DSMBs will be communicating in the near future to share information and generate a recommendation for the IPERGAY protocol.
AVAC will be following developments and providing updates as more information becomes available, please watch the blog and also check out our resources on avac.org/prep and prepwatch.org. We congratulate the PROUD team and recognize with gratitude the commitment and contributions of all of the trial participants.