Mapping Pathways is a multi-national project to develop and nurture a research-driven, community-led global understanding of the emerging evidence base around the adoption of antiretroviral-based prevention strategies to end the HIV/AIDS epidemic. The evidence base is more than results from clinical trials - it must include stakeholder and community perspectives as well.

14 May 2011

FEM-PrEP CLOSURE UPDATE: What does “futility” mean exactly?

It’s only been a few months into 2011, and last year’s trend of headline-making PrEP-related news continues. Last month, the FEM-PrEP trial was halted due to futility. This means that it was determined the study could not answer the question of whether daily Truvada worked, or not, in terms of preventing HIV among the trial population. Click here for the Mapping Pathways post on the trial closure.

Data collection for a final endpoint analyses report has begun. According to sources from Family Health International (FHI), primary endpoint data gathering will continue till around August 2011, and a final analysis of the primary endpoint and some secondary analyses can be expected to be completed by the end of this year. See more about the objectives and endpoints for these analyses here.

Meanwhile, as we await this report, many interesting conversations have been taking place about possible causes for the trial’s closure and what this might mean for the big picture on PrEP. How will this affect other similar trials, such as the VOICE trial, which is underway? What about future biomedical trials? What caused FEM-PrEP to be unable to answer the central question of the trial and be deemed “futile”⎯was it biological gender differences in drug activity and route of exposure, socio-cultural factors or simply flaws in the study design? How big a factor was adherence, and what lessons can we learn for future trials to create better ways of monitoring and encouraging adherence?

“There’s still so much we don’t know, and these are open questions rather than being settled questions,” remarked Julie Davids, Director of National Advocacy and Mobilization and lead coordinator of the HIV Prevention Justice Alliance from the AIDS Foundation of Chicago, a Mapping Pathways partner organisation. Davids, who observed that a “healthy conversation” was now happening among advocates, people living with HIV, researchers and others, also commented on the idea of “futility”: “‘Futility’ in common usage sounds really bad; outside the trial context, it means ‘hopeless.’ But in fact, in the trial context, ‘futility’ is not a definitive answer. It simply means that we don’t yet know and this way we’re proceeding is not going to answer the question⎯we can’t prove that the intervention worked, and we can’t prove that the intervention didn’t work … There are still things to be learned.”

John S. James from AIDS Treatment News looked at the trial’s closure from a behavioral point of view, discussing the need for science to take socio-cultural factors into account: “The iPrEx trial worked much better at the U.S. sites (Boston and San Francisco) than at other sites, where participants would often have strong reason to give their medication to someone who was sick due to HIV, and not tell the researchers. All of the FEM-PrEP sites were in Africa, where access to life-saving HIV treatment is much worse than in Boston or San Francisco. Unlike iPrEx, FEM-PrEP had no U.S., European, or other sites where no one would need to divert the pills to save the life of a family member or friend.”

Read on for a lively discussion on the how’s, why’s and what-if’s of FEM-PrEP


A membership listserv (run by IRMA – International Rectal Microbicide Advocates) was the forum for a lively and dynamic discussion among individuals from all parts of the prevention advocacy world trying to make sense of the FEM-PrEP trial closure.

“Something different/unexpected has happened here,” one IRMA member remarked. Added another, “I think this is all really part of a much bigger set of issues that derive from a naive assumption that we can translate HIV prevention research on one particular population and its cultural/behavioral/economic contexts to a totally different population without first understanding the sources of the new population’s HIV risks and contexts.”

Is it a guy-girl thing?
Gender differences in routes of transmission during sexual intercourse (i.e., vaginal vs. rectal) might also have played a factor, conjectured some. One member from North America wondered, “I'm curious about how anal intercourse (AI) was tracked. AI is the most efficient route of transmission, hard to study, hard to fund, and the most often overlooked variable.” This question gains relevancy considering FEM-PrEP was a women-only trial, as compared to iPrEx, which studied men who have sex with men (MSM).

Another European member said, “IF there is a notable difference in biodistribution between men and women and IF this difference contributes to the effectiveness of ARV for prevention (in one way or another), then planned trials need to ensure that this is taken into account in the design of the study.”

To adhere or not to adhere?
Others felt that study-design factors, such as the way study participants’ adherence was monitored, were additional issues that could have lead to the trial being deemed “futile.” One member asked, “Was this adherence measured by blood levels? Or self-reported? I am guessing the latter since such good adherence in reality (as measured by blood levels) is unprecedented. And, as we all know, self-reported adherence data by itself is pretty unreliable.”

Yet another IRMA member observed that, “The 95% adherence figure has already been revised downwards in that it was self-reported adherence.” (See the FHI fact sheet on adherence for FEM PrEP here.)

“How many more critical and expensive trials will rely on self-report
adherence? It is really too bad,” added another.

Voicing hope
For IRMA members in Africa, the focus was on the VOICE trial and how it will fare after FEM-PrEP. On hearing recent news that the VOICE trial would continue without alteration and as planned, one African member wondered: “Can one speculate that they are finding some effectiveness? I know. Too early, too soon… but what does this mean after FEM-PrEP? Just trying to do what shouldn’t be done… speculate, when should just be patient.” Another IRMA member in South Africa underlined the need to just “wait and watch.”

Perhaps the best perspective to this discussion came from an IRMA member with an expertise in biomedical trials, “I agree we all need to pay attention to design and try our best to ensure a range of behavioral and biomedical sciences bring considerations to protocol teams. I would just encourage all of us to remember that we have learned a lot in the last 24 months. Our lens today differs greatly from design concerns we would have expressed a short 24 months ago.” Added a fellow IRMA member, “Though the FEM-PrEP results are disappointing, they are calling for further thinking and confirm the need for further studies in diverse populations and settings … One trial can't give you the answer! Results are not always generalizable. These are exciting times!”

Read here about the exciting results from a new study that "confirms ARV treatment is a powerful prevention tool."

Click here to read about one organization's case against investing in PrEP right now. 

Learn more about current ongoing PrEP trials here.

You can also listen to a recording of a global civil society teleconference on the FEM-PrEP announcement here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

No comments:

Post a Comment