Five hundred twenty-five thousand six hundred minutes: How do you measure a year?

Original content from the Mapping Pathways blog team

Another year winds down, and it is time to take stock, to reflect on all the moments that have made 2011 an important year for the HIV prevention community – and for all those of us who hope for and work toward the end of the HIV/AIDS epidemic.

The year began on a high note: the extremely encouraging results from the IPrEx and CAPRISA trials, announced in 2010, had us “jumping up and down” as Jim Pickett (Director of Prevention Advocacy and Gay Men's Health at the AIDS Foundation of Chicago, chair of International Rectal Microbicide Advocates [IRMA], and a member of the Mapping Pathways team) says in his memorable interview, Success! Now What? These results were the long-awaited proof of concept for new prevention technologies – the “first real ‘win’” after many years of hard work.

The first bump in the road was the discontinuation of the FEM-PrEP trial in April due to futility, when the trial’s Independent Data Monitoring Committee concluded that the study would be highly unlikely to prove the effectiveness of Truvada in preventing HIV infection among the study population, i.e., HIV-negative women who are at risk of infection through sexual transmission.

The unexpected development had everyone expressing their opinions and wondering about the implications – after all, what does “futility” mean exactly? Dr. Linda-Gail Bekker (an expert in the field of biomedical trials and research) cautioned against knee-jerk reactions to the trial closure in her interview with Mapping Pathways: “Wait for the evidence, I think that is the message. Extrapolate at your peril. We know only what we know, and we need to just work within that.”

Then came the HPTN 052 results – and we were jumping with excitement again! The study demonstrated that initiation of ART by HIV-infected individuals substantially protected their HIV-uninfected sexual partners from acquiring HIV infection, with a 96 percent reduction in risk of HIV transmission. In an interview with Mapping Pathways, microbicides expert Joe Romano captured the overall sentiment, saying, “The level of efficacy seen in the HPTN052 study is stunning, and is extremely important on several fronts.”

There was good news for India (a Mapping Pathways target country) too: a UNAIDS report stated that the rate of new HIV infections fell by more than 50% in India between 2001 and 2009, double of the average decline in the world. The PrEP debate in India continued through the year. “There is a lot of concern in the country, especially with global funding not available right now,” explains Anjali Gopalan (Executive Director of NAZ India, a Mapping Pathways partner organization), in Notes from India: Concerns and Challenges Around PrEP. Mapping Pathways also published a short post on what we’ve been hearing in India so far.

Soon after the HPTN 052 results, the FACTS 001 trial was announced in South Africa – a follow-up study to confirm the effectiveness of tenofovir and to verify the CAPRISA 004 results in “larger, more diverse populations.”

Around this time, Mark Chataway (co-chairman of Baird’s CMC, a Mapping Pathways partner organization) was in South Africa (a Mapping Pathways target country). “My visit to the country once again brought into sharp focus for me just how significant South Africa and the rest of the southern African region are in the context of HIV treatment and prevention strategies,” writes Mark in his insightful post about South Africa and the HIV epidemic.

July brought bad news: the drought in the Horn of Africa began, bringing the region into international focus as an estimated 11.6 million people struggled for basic nutrition and sanitation in the humanitarian crisis – experts have warned that this situation could have a serious effect on the health of people undergoing HIV treatment.

Prevention trials continued to stay in the news. The Partners PrEP study and the TDF2 Botswana study both showed that taking antiretrovirals can reduce the risk of HIV infection through sexual intercourse by 62-73 percent among heterosexual individuals and heterosexual couples.

As heartening news continued to pour in, the UK’s House of Lords Select Committee on HIV & AIDS gave us another reason to celebrate as they called for greater emphasis and funding toward prevention. “Prevention must be the key policy,” remarked Lord Fowler, chairman of the committee.

In the US, dollars-and-cents issues remained a key factor. “The entire HIV prevention and treatment landscape overall is also in a state of flux in the US … When we get to the end of the day, there are good ideas, and then there are good ideas that are fully funded,” explains Julie Davids (Director of National Advocacy and Mobilization at AIDS Foundation of Chicago, a Mapping Pathways partner organization) in The Economic Effect: HIV/AIDS in the US.

October brought news that rekindled an old debate: the Lancet published the results of a study conducted in Africa, which seemed to suggest that hormonal methods of contraception could lead to increased risk of HIV infection. “Now whether this is a disaster or not, that needs to be considered very carefully in context. There are huge benefits, particularly in the African region, of avoiding an unwanted pregnancy, not only for the morbidity issues but also for mortality reasons … Firstly, we need to work out whether this result is true or not,” points out Dr. Tim Farley (an expert in HIV and sexual and reproductive health) in Hormonal Contraceptives and HIV Prevention: The Grey Area.

Recently, the VOICE trial hit a speed bump: the oral tenofovir arm and the tenofovir vaginal gel arm were dropped from the study. Both decisions were based on reviews of study data, which concluded that they would not be able to demonstrate effectiveness in preventing HIV among the women in the trial (although both products were found to be safe). The reasons for this are still unclear and will be fully investigated when the trial concludes in the middle of 20112. The study continues to examine the oral Truvada tablet to determine whether it’s effective in preventing HIV in the trial population.

A recent highlight was US Secretary of State Hillary Clinton’s speech on HIV/AIDS – one that earned her both bouquets and brickbats from the HIV prevention community. On the upside, Secretary Clinton focused on scientific evidence and called for immediate action to take advantage of the “historic opportunity” to create an “AIDS-free generation.” Unfortunately, she completely omitted any reference to PrEP and rectal microbicides. The speech also failed to mention gay and MSM populations, two groups that are experiencing catastrophic rates of HIV globally.

The year wound up with IRMA’s rectal microbicide African strategy meeting and the big ICASA conference in Addis Ababa, Ethiopia in December. (Click here and here to read about some of the important developments at these events.)

All in all, 2011 has been a dynamic year: lots of excellent news as well as some troubling developments. From the Mapping Pathways blog team, here’s to celebrating our achievements, learning from our failures, and working to address the challenges.

Happy New Year!

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

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

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