Providing a range of prevention options: In conversation with Linda-Gail Bekker

Original content from our Mapping Pathways blog team

We need options. Not everyone in the world is a good pill taker. Like so many things in life, we may realise that people need different prevention options since they have different personalities.

In the final part of this five-part series, Linda-Gail Bekker of the Desmond Tutu HIV Centre, a Mapping Pathways partner organisation, speaks about the importance of adherence, both in clinical trials and the real world, and the challenges and issues facing adolescents. Read parts one, two, three and four

MP: You have mentioned adolescents as a particular vulnerable group in South Africa. In an interview conducted earlier this year, your colleague, Dr. Melissa Wallace, also talked about adolescents as an especially at-risk group. What are some factors that make them so vulnerable?

LGB: One particular reason why adolescents are highly at risk for HIV is because many are at the stage of their lives where they may be experimenting with their sexuality. They may also find themselves in relationships where negotiating condoms may be incredibly difficult.

This maybe the case with younger women whose relationships can be with older men and young MSM outing themselves for the first time and who may then choose to go out with older men.  In that situation, being able to use a PrEP tablet discreetly and under their own control could be a life-saving step.

So putting prevention into the hands of the vulnerable becomes a very important tool. But we can only do this if we are sure it’s safe in this population, which requires carefully run clinical research in order to adequately test the product in the relevant populations.

This requires resources and investment from sponsors and funding agencies even though this is often regarded as “high risk investment”. In that regard, I’m delighted that we’ll be starting an MP3 project (methods of prevention) based on a grant awarded to us by the National Institutes of Health (NIH) to look at PrEP and other biomedical prevention modalities in adolescents between 14-17 years old.

MP: Adherence is an issue that has come up quite a bit this year, from M2012 to AIDS 2012. How much are people talking about adherence and about taking lessons learned from trials into the real world?

LGB: Adherence is the Achilles heel of the HIV prevention and treatment worlds. This is where biology meets behavior. We know that the pill is efficacious – Partners PrEP showed that beautifully. In fact, every single one of the clinical trials has shown that once adherence increases there is a direct correlation with efficacy in the results. Starting with the 39% in the CAPRISA study leading on to 44% in the iPrEx study and going on to an astounding 75% in the Partners PrEP study – each one had an increased overall adherence rate and with this an increase in point efficacy, so the correlation appears to be a real phenomenon.

In addition, the sub-studies done in every trial showed that high adherers within a study had a better efficacy compared to the lower adherers. So we can quite confidently say there is a robust relationship between adherence and efficacy.

So how do we get people to adhere? Motivations play a great role. Partners PrEP which enrolled discordant couples had a great in-built motivation that one was protecting a loved one by taking the pill, which may be the reason we saw particularly high adherence for that population.

I think we also need to understand that not everybody in this world is a good pill-taker. There will be those who just cannot bring themselves to swallow pills on a daily basis. So PrEP may not be a very good idea for them. In that situation, maybe a rectal microbicide or a microbicide that’s part of a lubricant may work very well for that individual.

We need options. If we get to that stage in the future where other prevention technologies are available, like getting a shot in the arm that lasts three months, then we need that option on the table too. Like so many things in life, we may realise that people need different prevention options since they have different personalities.

MP: What are some of your final thoughts on what needs to happen to stem the HIV epidemic?

LGB: We need to have conversations on several different levels: ethical, scientific, public health, politics and priorities. Different countries and communities will be at different places. Some of the hard questions are : Who pays? How will we implement this prevention strategy? Is this strategy for the generalised epidemic or is it only for selected key populations? Who are the key populations? What are the social factors that make them vulnerable? Is this ethical? Does it make sound public health sense? What wont be afforded if we go this route? Who will benefit if we do?

Those are all very hard questions but they deserve to be asked and certainly require ongoing dialogue. This brings us back to the Mapping Pathway- we have been contributing to the dialogue through this project. We also need to do the modeling exercises and implement some feasibility type projects and then continue to raise more questions., It’s a wonderful thing that we are at a point where we can actually have these conversations. They are not hypothetical questions anymore. It is urgent to have these discussions in such a way that the next steps become clear and infections can be averted before too much more time is lost.

Linda-Gail Bekker is deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town. She also serves as the chief operating officer of the Desmond Tutu HIV Foundation, a Mapping Pathways partner organisation. 

Stay tuned for the Mapping Pathways monograph, coming in early 2013

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

AIDS 2012 and FDA approval: Seminal events in the world of HIV prevention

Original content from the Mapping Pathways blog team

Even in the dynamic world of HIV prevention, July 2012 is already a landmark month – even before nearly 25,000 people descend on Washington, DC for the International AIDS Conference (AIDS 2012).

The news that has most advocates and program implementers excited is the U.S. Food and Drug Administration (FDA) approval of a new prevention indication for Truvada, an ARV drug commonly used for HIV treatment. Truvada can now officially be used as PrEP (pre-exposure prophylaxis) for people at high risk of acquiring HIV through sexual activity. These “at-risk” individuals include HIV-uninfected gay men and other men who have sex with men (MSM) and HIV-uninfected partners in seriodiscordant relationships.

In approving Truvada for PrEP, the FDA followed the recommendation of a panel of experts that voted to approve the drug on May 10.

Here is what the new Truvada label and prescribing information will look like.

The FDA directed drug maker, Gilead Sciences, to come up with a Risk Evaluation and Mitigation Strategy (REMS) to minimize the risk to uninfected individuals of acquiring HIV infection and to reduce the risk of resistance.

Some concerns remain, the most crucial of them being cost. Truvada is not a cheap drug – costing as high as $13,000 a year retail in the United States (it is available as a generic for a fraction of this cost outside the U.S.) – and it will be a challenge to get the drug to the most “at risk” groups, many of whom lack access to any healthcare. Adherence support, behavioral counseling, and regular HIV testing and monitoring for potential drug toxicities will also be very important. It is clear that PrEP needs to be embedded in a holistic healthcare construct – and it’s much more than individuals simply taking a pill every day.

Addressing these issues (and others) are paramount, and will occupy the energies of advocates, researchers and community organisers, many of whom will convene and share findings at AIDS 2012.

AIDS 2012, the “granddaddy of all conferences,” according to Jim Pickett, Director of Prevention Advocacy and Gay Men’s Health at the AIDS Foundation of Chicago, is a great opportunity for the Mapping Pathways project to disseminate information and findings.

The Mapping Pathways team will be participating in a number of sessions at AIDS 2012 starting with a satellite session on Sunday, July 22 titled “From Revolution to Reality: How Will New Science Impact the U.S. National HIV/AIDS Strategy?” Molly Morgan Jones from RAND Europe, a Mapping Pathways partner organisation, will be one of the presenters in this session and will share analyses specific to PrEP in the U.S. context. .

Jones, along with other Mapping Pathways team members, will also be presenting two new posters at AIDS 2012, which will include information gathered from the community surveys, policy interviews, the literature review and the ExpertLens.

Presentation slides and posters will be featured on the blog during the conference.

Stay tuned to the blog as we continue to bring you updates from AIDS 2012 as well as reactions from advocates and stakeholders on the FDA approval of Truvada.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

PrEP: time to rethink prevention, effectiveness and ethics?

via Somatosphere, Marsha Rosengarten

One of the more controversial interventions proposed for HIV prevention in those who test HIV antibody negative and perceived to be at risk is pre-exposure prophylaxis (PrEP) – a daily pill comprising one or two antiretroviral drugs manufactured by Gilead Inc.  Besides the mixed results from multi-site randomised controlled trials (RCTs) seeking to establish the efficacy of PrEP (see iPrEX versus Fem-PrEP), concerns have been raised about PrEP’s potential to undermine condom use, its cost implications in locales where treatment provision is still lacking and elsewhere, its potential to cause unwanted drug side-effects as well as possible drug resistance in those it fails to protect.

Nevertheless, continuing new infections and evidence that high adherence produces a strong protective effect are mobilising many public health authorities to devise feasible implementation models.

Most remarkable about the growing interest in PrEP is the exclusion of the social sciences from major forums where this work is taking place.  One such example is a two-day forum held in the UK by IAPAC on the dual topics of treatment as prevention (TasP) and PrEP.  The only non-biomedical speakers listed on the programme were a psychologist (speaking on adherence), a bioethicist, activists and public health officials linked to various national epidemics.

Indeed it won’t come as a surprise to many to know that despite the millions of dollars to support RCTs for PrEP, the Bill and Melinda Gates Foundation have so far declined to support a substantial programme of social research on PrEP.  In fact if we consider the bioethical requirements imposed on the conduct of RCTs for PrEP and other biomedical interventions, there is no ethical requirement for research on the social dimensions of the intervention during or post RCTs. This applies even when RCTs demonstrate candidate efficacy.

Read the Rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

FDA Panel Approval – A Giant Step for HIV Prevention

Original content from the Mapping Pathways blog team

An important landmark was achieved on May 10 when a panel of experts of the U.S. Food and Drug Administration (FDA) strongly backed the approval of the first ever drug to prevent sexually acquired HIV infection.

The panel recommended approval of Truvada (emtricitabine/tenofovirdisoproxilfumarate) for use in PrEP in HIV-uninfected gay men and other men who have sex with men (MSM), HIV-uninfected partners in serodiscordant relationships and other individuals “at risk” of acquiring HIV through sexual activity. The committee voted 19 to 3 in favor of using it for HIV-uninfected gay/MSM, 19 to 2 (1 abstention) in favor of using it for HIV-uninfected partners of those with HIV, and 12 to 8 (2 abstentions) in favor of using it for other “at risk” individuals.

The webcast can be viewed here and copies of all the slide presentations are here.

While the FDA is not required to follow the panel’s advice, it usually does and the final decision is expected by June 15.

One of the main drivers of HIV transmission in the U.S. is unprotected anal intercourse among gay men and other men who have sex with men (MSM), who represent approximately 2% of the population but accounted for 61% of all new HIV infections in 2009, according to the U.S. Centers for Disease Control and Prevention (CDC.) CDC estimates approximately 1.2 million people currently living with HIV in the U.S., and about 50,000 new infections every year. Click here for more info on the U.S. epidemic.

To support its supplemental drug application, Gilead Sciences presented findings from the iPrEx trial and the Partners PrEP trial, both of which used Truvada in combination with regular HIV testing and counseling. Condoms and STD screening and treatment were also part of the "prevention package" for all trial participants.

The iPrEX trial indicated that gay/MSM participants who took Truvada daily had a 44% reduction in HIV incidence over the course of 1.2 years of follow-up compared with placebo. However, there was low adherence to the drug with approximately half the men not taking their pills, despite extensive counseling and other supportive measures.  For individuals who did take the drug, and had detectable levels of drug in their bodies, the efficacy of Truvada was approximately 90%. The Partners PrEP trial (serodiscordant heterosexual couples in Africa) had encouraging results as well with risk of infection reduced by 73% in those who received Truvada and demonstrated astoundingly high levels of adherence.

Adherence was, once again, a major topic of debate among the panel members who pointed out that taking the pill every single day was critical for the efficacy of Truvada. If in controlled, clinical trials, patients were not able to take the drug everyday, how could one ensure that they would take the drug everyday in the real world, where people are more likely to forget or skip their medication?

Another concern voiced by the panel members was whether the use of Truvada would encourage higher-risk behavior among users, like neglecting to use a condom, which is still the most reliable defense against HIV. (Read an interesting response to this concern by some members of the HIV prevention community here.)

The potential FDA approval will allow Gilead to officially market Truvada as an HIV-prevention strategy. As our Mapping Pathways colleague Jessica Terlikowski said last week,“We need to make sure that people are aware of what prevention strategies exist, so they can access what they need when they need it. We owe it to the communities to push for both existing tools like male and female condoms, sterile syringes, PEP, as well as emerging biomedical tools like microbicides and PrEP.”

The issue of whether the FDA should approve Truvada for use in PrEP continues to be a source of debate and conversation among the HIV prevention community.

To learn more about PrEP, check out the following links:

PrEP Watch

“Getting Practical About PrEP,” by David Evans in POZ Magazine.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

AIDSmeds: Adherence Challenges in Intermittent HIV PrEP Study

via AIDSmeds.com

Intermittent use of Truvada (tenofovir plus emtricitabine) as pre-exposure prophylaxis was associated with poor adherence, compared with daily use of the tablet to prevent HIV infection, according to results of a small clinical trial published in the online scientific journal PLoS ONE.

Using electronic pill caps, the Kenyan study found that the adherence rate associated with daily PrEP use was 83 percent. Among those using intermittent therapy—Truvada taken on Monday, Friday and within two hours following sexual intercourse—the adherence rate was 55 percent. Among those who only took Truvada within two hours following sexual intercourse, the post-coital adherence rate was only 26 percent.

Truvada as PrEP was recently recommended for U.S. Food and Drug Administration (FDA) approval by the Antiviral Drugs Advisory Committee. The recommendation is based on data from several clinical trials, all exploring the safety and efficacy of Truvada PrEP used daily.

There has been interest in exploring alternative dosing strategies, notably scheduled and as-needed intermittent use of the drug. Experts hypothesize less frequent dosing may reduce the risk of side effects and prove easier for people to use, in light of the poor adherence that has been noted in clinical trials evaluating daily use of Truvada.

Read the Rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

Microbicides 2012 Conference: “Someday, our ARV-prevention tools will be as sexy as the I-Phone!”

Original content from the Mapping Pathways blog team

This is the second part of a two-part blog series on highlights and discussions from the Microbicides 2012 conference that recently concluded in Sydney. Here, Jim Pickett re-emphasizes the importance of adherence in clinical trials (a big topic of discussion at the conference) and his optimism about the future of the HIV prevention and treatment landscape. Read Part I here.

MP: Can you give us some examples that illustrate the issues surrounding adherence?

JP: The Partners PrEP trial and the FEM-PrEP trial are good case studies to illustrate the issues surrounding adherence in an HIV prevention clinical trial. Partners PrEP reported very high levels of adherence while the FEM-PrEP trial had to be stopped in April 2011 due to “futility.” Studies later indicated that while many of the FEM-PrEP participants said they adhered to the medication schedule, blood tests indicated that many did not.

A built-in support system and the risk perception of participants are the key here. In Partners PrEP, serodiscordant couples were enrolled together into the trial. One partner was HIV positive while the other was negative. The HIV risk of the HIV-negative partner was not theoretical; it was real. HIV was in their life and they were in it together.

FEM-PrEP involved women recruited on their own, with no consideration whether they were in a serodiscordant relationship – or any relationship for that matter. The risk of HIV was not present in the form of a partner who already had it, but it was, in fact, present in their environment where there was very high HIV incidenceIV HIV . It is interesting that many of these women did not believe themselves to be at a high risk of HIV, despite this high incidence.

Human beings are very good at rationalizing risks and saying “it can never happen to us.” I can drive fast and will never get into a car accident. If I feel a certain behavior is not risky, or that I can “get away with it”, I will not take steps to protect myself.

We don’t want to create tools where only people who are married or in a relationship are able to use the tools successfully. That would be crazy. But we do have to think about how important those social relationships are and use the lessons learned to devise new tools and new trials that give us answers – and develop things that work for all kinds of people, regardless of relationship status, sexual orientation, or whether their potential HIV exposure comes from unprotected vaginal intercourse, unprotected anal intercourse, or from the sharing of syringes during injection drug use.

MP: Are there any trials coming up that you are excited about?

JP: I’m very excited by the upcoming MTN-017 rectal microbicide safety and acceptability trial that will enroll approximately 186 gay men, other men who have sex with men, and transgender women at trial sites in South Africa, Peru, Thailand, and the United States. Participants will go through three eight-week cycles: One cycle of having a daily Truvada tablet, another cycle of applying a “rectal friendly” reformulated tenofovir gel every day, and a cycle of applying the gel before and after having sex.

What impresses me is the level of community involvement sought and obtained to help design this trial. The trial team, and advocates such as myself, visited each of the sites mentioned, had day-long meetings with community members, captured all their observations, and made adjustments to the trial design from the input received. We have to listen to the voices of the communities. We can’t just show up and conduct trials.

MP: What are your other thoughts on the HIV prevention and treatment landscape?

JP: I always like to compare the HIV prevention and treatment landscape to the evolution of computers and phones. Years ago, computers were the size of a house. It took time for the computer to evolve from its clunky beginnings to its current look where we can carry it around in our pocket and it can do more things than we ever could have imagined. Now we have phones and computers that are completely intuitive and easy to use.

Similarly, the HIV landscape has evolved over the years. Before 1996, we had a handful of drugs that didn’t always work great. They were toxic and had to be taken multiple times a day. When protease inhibitors came out in 1996, people near death’s door were brought back to life. But they also had to suffer through a whole host of side effects like nausea, diarrhea, and body disfigurements.

Now, new-age ARV medication can combine three drugs into one pill that has to be taken just once a day. The side effects are minimal and you don’t have to worry about requirements like eating it on a full or empty stomach, or having it refrigerated.

We are now in the clunky computer stage of ARV-based prevention. But, things will keep getting better. We can’t get to the streamlined phase before going through the clunky phase. We have to learn to crawl before we can run. Someday, our ARV prevention tools will be as sexy as the iPhone.

Jim Pickett is the Director of Prevention Advocacy and Gay Men's Health at the AIDS Foundation of Chicago. He is chair of IRMA (International Rectal Microbicide Advocates), and a member of the Mapping Pathways team. Read Part I of Jim’s interview here.

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