ARM-ing Africa for Rectal Microbicides

Original content from the Mapping Pathways blog team

These are exciting times in the HIV-prevention landscape.  In an earlier Mapping Pathways post, we covered our colleague, Jim Pickett’s experiences at the Microbicides 2012 (M2012) conference in Sydney in April.  At M2012, advocates discussed a number of important issues, including the importance of adherence in clinical trials. 

A major development at M2012 was a report released by the International Rectal Microbicide Advocates (IRMA), a global network that Jim leads, as a cornerstone of their Project ARM (Africa for Rectal Microbicides). The report, titled “On the Map: Ensuring Africa’s place in Rectal Microbicide Research and Advocacy” outlines priority actions to ensure Africa is involved in rectal microbicide research and advocacy activities.

On The Map is the result of a two-day consultation that took place before the ICASA conference in Addis Ababa in December with African and international stakeholders. Says Pickett, “The central question of the consultation was ‘How can we be more strategic and proactive to make sure Africa is on the map when it comes to rectal microbicide research and advocacy?’”

The Project ARM report lays out seven key action areas specific to rectal microbicide research and advocacy in the African context:

Knowledge, Attitudes and Behaviors (KAB) studies on anal health and anal sex to generate data that can be analyzed across countries and populations

Rectal microbicide acceptability studies

Mapping of sex education curricula to determine what content on anal health is included

Advocacy for lubricant access through the “And Lube” campaign of the Global Lube Advocacy Mobilisation (GLAM)

Documentation of best practices for integrating anal health, anal intercourse and rectal microbicides into sexual health and HIV prevention education

Capacity-building activities for community leaders, advocates, and researchers

Awareness raising and education about anal health, anal intercourse, and rectal microbicides, including development of educational materials and other communications efforts specific to the African context

According to Pickett, members of the Project ARM working group further prioritized the key activities. While the members agreed that all the activities are important, the top three are the KAB studies, awareness raising and education on anal health and anal intercourse, and improving access to condom-compatible lubricants, which are in very short supply across most of Africa.

Pickett explained that the HIV epidemic in Africa is often wrongly considered as solely heterosexual, with sexual transmission driven entirely by unprotected vaginal sex between men and women. “There has been little to no official recognition of the fact that there are gay men and other men who have sex with men in Africa who are enduring high rates of HIV, and that plenty of heterosexuals also have anal sex. Unprotected anal intercourse is 10 to 20 times more likely to result in an HIV infection compared to unprotected vaginal intercourse,” says Pickett.

As mentioned, increasing access to condom-compatible lubricant is a key goal of Project ARM. Access to appropriate lubricants on the continent is quite abysmal. “In the absence of appropriate, safe lubricants, people use things like shampoo, cooking oil, hand lotion, antibiotic creams – even motor oil – that break down the latex in the condom, erasing the protective benefits.. People also use saliva, which dries out quickly – and can cause tears in the condom as well as harm the fragile rectal environment. For safer anal sex, lubrication that is condom-compatible is absolutely necessary,” says Pickett.

 “There is an immediate need for appropriate lubricants for people who have anal intercourse in Africa. If we can’t get lubricant to people now, how will we be able to deliver rectal microbicides to them when they become available? Increasing access to appropriate lube is absolutely critical, and paves the way for access to rectal microbicides down the line. We can’t have campaigns and programs that deliver condoms without also delivering condom-compatible lubes. Period.”

Stay tuned to the blog as we bring you more information on this exciting project. Until then, read a vivid snapshot of advocacy in Africa through the eyes of Brian Kanyemba here. Brian has been very involved with IRMA's Project ARM, and is an integral member of the Project ARM video working group, which is trying to produce an African-focused video on anal health and anal intercourse.

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Fenway Health Report: The Implementation of PrEP in the Fight Against HIV

viaFenway Health

Pre-exposure chemoprophylaxis (PrEP)—taking antiretroviral medications to prevent HIV transmission—could be a “game changer” for HIV prevention. PrEP has demonstrated partial efficacy with men who have sex with men (MSM), transgender women, and heterosexuals in several recent studies. Recent modeling of PrEP implementation coupled with scaled up treatment predicts that PrEP could significantly reduce HIV incidence and prevalence. And if PrEP is accompanied by sustained care, behavioral interventions, and safety monitoring, PrEP need not lead to increased sexual risk behavior or drug resistance.

The latest Policy Focus from The Fenway Insitute summarizes the state of PrEP and microbicides research as of January 2012, looks at willingness to use PrEP among various populations, addresses concerns about PrEP that could present obstacles to implementation, offers strategies for effective implementation, and examines policy issues related to cost and how to make PrEP accessible to those most vulnerable to HIV.

The Fenway Institute’s analysis found that the most effective prevention interventions will be those that combine behavioral interventions, structural interventions, and emerging biomedical technologies, such as PrEP and microbicides. The analysis concludes with recommendations for implementation of PrEP, including:

■If the U.S. Food and Drug Administration (FDA), which is considering approving FTC-TDF for use as PrEP, feels that research on PrEP’s efficacy among heterosexuals is inconclusive, it should consider approving PrEP for MSM now separately and consider heterosexuals, IDUs and other populations in the near future as the science advances;

■The World Health Organization (WHO) should issue guidance on PrEP that takes into account the promising results of the iPrEx study, Partners PrEP, and the Botswana CDC study;

■Following the release of the Bangkok injection drug user (IDU) trial results, if appropriate the U.S. Centers for Disease Control and Prevention, the U.S. Public Health Service, and the WHO should issue guidance for PrEP with IDUs.;

■States should provide access to PrEP as a critical prevention service and prescription medication under the Essential Health Benefits provision of the Affordable Care Act;

■State Medicaid programs should also cover PrEP as a cost-saving measure that will improve public health and ultimately save money in health care costs;

■Provision of PrEP to MSM and transgender women should occur in a broader context of ensuring clinically competent health care to gay, lesbian, bisexual and transgender people.

Read the Full Report.


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

In Conversation with Kate Morrow: Of Microbicides, Sensations, and Adherence (Part 2)

Original content from the Mapping Pathways blog team

Kathleen (Kate) Morrow is a staff psychologist at the Miriam Hospital and an associate professor (research) of Psychiatry and Human Behavior at the Alpert Medical School of Brown University. She is driving two innovative microbicide projects – Project LINK and Project MIST. Kate is also a member of the IRMA Steering Committee.

(In Part 1 of this interview, Kate talked about Project LINK and how she got started down this career path.)

MP: Could you describe your work with Project MIST? How does it broaden the scope of your earlier work with Project LINK?

KM: Like Project LINK, Project MIST is also part of the Microbicides Innovation Program. I’m doing the acceptability piece on that project, whose Principal Investigator is Robert Buckheit at ImQuest BioSciences. Out of Project LINK, we understood that women could feel the differences among various gels well enough to discern, with their ratings, one product from another. The women finally had a choice to make at the end of the study. Their experiences impacted the product they chose – different women chose different experiences.

We’re in the process of completing LINK analyses now, and one of the things we feel like we don’t have a handle on is how gel volume would play into, and impact, a woman’s perception and experience with a product. So, if we had the exact same gel, but in different volumes, would she experience different things? That’s a question in the field as well – how much gel do we need to apply? That depends on the dosage, the amount of drugs in each measure of gel. That’s still an open question – and we decided we needed to answer that question from the perspective of the user, so that, if we could, we could optimize the volume for drug delivery, as well as the user experience.

And for me, the big question hanging out there was – what do the guys think? From LINK, we now know what women feel and what they think about those feelings and sensations, but we don’t have any understanding of what their male partners feel and how that will drive their preferences for gels.

Last but not least, MIST also gave us the opportunity to try a quick-dissolving film developed by Lisa Rohan at the University of Pittsburgh. So, we’re looking at those three issues in Project MIST: volume and the difference between a gel and a film with respect to user experiences, and exploring male sexual partners’ sensory perceptions and experiences. Like LINK, it’s a mix method study: this time we’re incorporating the male partners into the qualitative data mix to understand their experiences.  We’ll continue to use the validated scales from LINK.

MP: What inspires you?

KM: Well, to begin with, there’s the work itself. I mean, I do this work because I think it’s really important – I think it’s a piece that’s missing otherwise from the field. There are some of us who focus on things like sexual pleasure (Anne Philpott among them), but we have to understand the mechanisms of sexual pleasure – how do we help with that process? These projects, LINK and MIST, uniquely do that. We’re very unique in the fact that what we are trying to understand is which sensory perceptions and experiences impact willingness to use a product and hopefully, down the line, adherence to product use. That way, we can better create a formula that will not only deliver the drug well, but also will make the sexual experience one that people will want to have – so they’ll continue to use the product. What gets me excited every day is trying to figure out that puzzle, and hoping that in the long run this work will have a beneficial impact on the field and our ability to end the HIV epidemic.

But, you know, research can get drab, it can drag along…you meet your small goals often but the big end points don’t come, I think, as often as we’d like them to! So it’s the little things every day that keep us going. I think the thing that inspires me the most in that sense is my participants. Personally, they’re not getting any benefit out of doing these studies with my team – they know it’s a placebo study. But they come in, they try the products, they give us their opinions… To me, they’re the experts, they’re the ones that are the key to my success and my ability to get the data in this field.

Since we started LINK, we’ve seen more than 400 women walk through our doors saying, “I want to help you do this.” They tried all the different products – and I know they weren’t all pleasant! Yet, our retention rate in the studies is well over 90% – it’s a group of women who really want this to happen. They’re dedicated, they try to be as honest as they can…you know, frankly, we ask them some difficult questions. In the qualitative interviews, they’re sitting across from us telling us the story of their experience – and that can’t be easy to do. At some level it’s got to be a little uncomfortable to talk about your sexual experiences in such detail. And now their male partners are also on board. They all understand the medical necessity of the study. They understand that a pleasurable sexual experience is important to microbicides and their ultimate use. I am constantly amazed by our participants.

MP: As a behavioral scientist, what is your role in this process?

KM: Well, it’s possible (in fact, it’s probable) that we will not be able to make one, single ideal microbicide for women. Everybody likes different things in sex, and people like different characteristics. What we’d like to do is raise the floor – get rid of the absolute bad characteristics and make the properties and performances of these gels good enough for people to use them.

Once we end up with a tolerable gel and begin to move into uptake and access and use, what we can then do as behavioral scientists is educate women and their partners about the not-so-great characteristics that might remain but that have to be there in order for the drug to be efficacious. It’s a balancing act between the experience of the user and the efficacy of the product. At some point, we’re likely to run into “we need it to be like this for the efficacy, we can’t change that”. So then, as a behavioral scientist, I have to say, “Okay, if you can’t change that, what impact is it going to have on the user and how can I help the user to cope with that?”

So, there are two things going on for me: on one hand, let’s make the best one possible to begin with. Then, if there are things we can’t change due to efficacy, how do I help people deal with those remaining issues? Even though it’s not going to be perfect, there are still things we can do as behavioral and social scientists to help deal with those imperfections.

MP: What’s the hardest part about your job?

KM: Not having enough time in the day! There’s just so much to do. I’d like it to move a whole lot faster than it can – but that’s just what it is. Obviously, I wish that we were there already. But day in and day out, I love my work. I love the science. I’m very appreciative of my participants and the efforts that they put in. My team is amazing and I think we’re doing good work and that we’ll be able to contribute, ultimately, to a better microbicide.

MP: What are you most excited about for 2012?

KM: Finishing up the LINK data and figuring out which of our scales are most useful to us in the process of evaluating candidate gels. And, of course, continuing with and finishing MIST and incorporating the male partner experience into the mix. Down the road, I’m hoping that we start a project to do similar kinds of science around rectal microbicides both with men who have sex with men (MSM) and women. I’m keeping my fingers crossed that it will get funded and take off this year. I’m just really excited about moving forward and trying to keep all of us moving forward.


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

In Conversation with Kate Morrow: Of Microbicides, Sensations, and Adherence (Part 1)

Original content from the Mapping Pathways blog team

Kathleen (Kate) Morrow is a staff psychologist at the Miriam Hospital and an associate professor (research) of Psychiatry and Human Behavior at the Alpert Medical School of Brown University. She is driving two innovative microbicide projects – Project LINK and Project MIST. Kate is also a member of the IRMA Steering Committee.



MP: What got you started down the path of HIV prevention?

KM: From a personal perspective, I spent much of the ’80s losing people to the epidemic – that was a very powerful experience in my life. Then, after I trained to become a clinical psychologist, I worked as a clinician in an outpatient substance abuse clinic and many of my patients were infected with HIV. At that point, I was a Masters level clinician. When I went back for my doctorate, I decided to study HIV prevention – and it’s been my work ever since.

MP: And how did microbicides come into the picture?

KM: In the course of my post-doctoral fellowship I was introduced to microbicides by my mentor, Ken Mayer. Like many people, I didn’t even know what a microbicide was at that point! He asked me to pursue the notion of acceptability and how these new products would fare in that regard. I became very interested in how that was going to work, and it just…suited me as far as what I wanted my career to be about. It was about so many things close to my heart – giving people (especially women) the power and control to prevent HIV, something that didn’t interfere with their lives… My work primarily focused on women to begin with. Ultimately, I’ve gotten involved in the broader reality of what microbicides will be (I hope!), including vaginal and rectal microbicides for both men and women.

In my work with acceptability, a big issue for me was that we were conceptually equating acceptability and adherence. It’s like we were saying if they adhere to it, it must be acceptable and if it’s acceptable they’ll adhere to it. In my mind, that’s not a given. I mean, I would love to believe that if it’s acceptable, everyone will use it – but I don’t think that’s necessarily true given the relational and contextual issues that surround microbicide use.

MP: What is Project LINK all about?

KM: Project LINK began in 2006. It is funded primarily by a grant from the National Institutes of Health, and was also supported by CONRAD. It is part of the NIH’s Microbicide Innovation Program.It is focused on the female user experience. The main idea is to try to understand how the formulation of a microbicide – the properties and characteristics of the gel itself – relates to the experiences the users have. The study involves approximately 350 women. The data collection is now complete, and we hope to have the results in the coming months.

We’ve been running into a lot of adherence issues across microbicides trials since the very beginning. LINK is trying to understand what the user experience is given the kind of formulations that they’re using and the properties of those formulations. Each product has its own constituents, its ingredients, and the way they interact with each other and with other external factors. If we can link these formulation characteristics to a woman’s experience, then maybe we can fix or enhance that experience and make it something that women can at least tolerate – if not enjoy.

MP: Could you explain with an example?

KM: Take, for example, leakage. Leakage is something that we always deal with when it comes to vaginal gels. Some gels leak while others are good at not leaking out. If leakage is a bad experience for women then we can alter the “recipe” of the formulation, so to speak, to minimize that leakage or to make it happen at a different, more preferable point in time. The idea is to figure out what women can feel and experience at a very sensory level, in their vaginas, and pinpoint which sensation is being driven by which of the gel’s properties or performance characteristics.

MP: What stage is Project LINK at currently? And what’s the end goal?

KM: We’ve developed a set of scales to show the range of different sensations and experiences reported by women when they use the products. Basically, these scales allow women to rate products given specific statements. We then tested four novel gels using these scales. The idea was to capture a range of women’s experiences from a relatively low-viscosity gel to a high-viscosity gel, along with other varying parameters (yield stress, dilutions properties, etc.). When the women had evaluated all four gels, at the end of their final visit in the study, they provided data on which formulation they would prefer. Their experiences impacted the product they chose – different women chose different experiences.

Now, we’re analyzing the data to understand the correspondence (hence, Project LINK) between the sensations and the properties of the gels. Once we’ve done that, we can try and make the microbicides feel better to the user – and make them work better, too. Obviously, the formulation is primarily about delivery and efficacy – to get the active ingredient where it needs to go, do what it needs to do, and stay there for as long as it needs to. That’s key. But if we can figure out how to make the best formulation for drug delivery and make it one that women can at least tolerate, if not like, then we have a better shot at effectiveness overall. If it feels good, women will use it.

Actually, there are two ways of looking at microbicide gels. First, you could think of it as a product with a neutral impact on the sexual experience – some people enjoy sex the way it is and don’t want it altered by a product. This would also be useful for women who need the microbicide to be covert. Second, you can develop a product that actually enhances sexual pleasure. Hopefully, if people like it, that would increase the likelihood of their using it. And if it’s efficacious to begin with, then that means we’re reducing the possibility for HIV infection.

Watch this space for Part 2 of this interview, where Kate talks about the broadening scope of her research in Project MIST, behavioral science, what inspires her, and the hardest part about her job.

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

FACTS 001: A Quick Update

 * Original content from our Mapping Pathways blog team

Remember the FACTS 001 trial that was announced in South Africa in June 2011? (Read our blog post on it if you don’t.) We are very happy to share an exciting update about it!

On October 21, 2011, the first study participant was enrolled in this Phase III clinical trial of vaginal tenofovir gel (a microbicide, meant to protect women against HIV infection). The Desmond Tutu HIV Foundation brought the first participant on board. Five sites have begun screening women, in Cape Town, Johannesburg, Soweto, Rustenburg, and Pretoria.

To give you a quick recap, this landmark trial is a large-scale, randomized, placebo-controlled clinical study that is meant to test the safety and confirm the effectiveness of tenofovir gel used before and after sex to protect women against HIV infection, as well as HSV-2 (a virus that causes genital herpes). A total of 2,200 HIV-negative women between 18-30 years of age are going to be enrolled across nine sites in South Africa.

Essentially, the aim is to verify the CAPRISA 004 results in "larger, more diverse populations". The trial is being conducted by FACTS (Follow-on African Consortium for Tenofovir Studies) and led by Professor Helen Rees, the Executive Director of WHRI (Wits Reproductive Health and HIV Institute). FACTS 001 is sponsored by CONRAD and funded by the South African Department of Science and Technology, the U.S. Agency for International Development (USAID) and the South African Department of Health. CONRAD and Gilead Sciences, Inc. are providing the study products.

So, why is this trial such a milestone in the world of HIV prevention? If this study, along with VOICE which is testing the use of tenofovir gel and oral Truvada tablets, confirms that tenofovir gel is safe and effective, it could lead to the first licensed vaginal microbicide product. Women would then have access to and be able to control this brand-new HIV prevention method. Truly revolutionary developments!

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

Tricky Terminology in HIV Prevention – Part 2: “Microbicides” and “Oral PrEP”

“I think elegance must take second seat to being clear and helping people absorb vast amounts of new information.”

We recently blogged about the terms “abstinence” and “being faithful” – words that have caused a great deal of controversy in the HIV prevention arena. In this post, we discuss another instance of tricky terminology – the need to maintain the distinction between “oral PrEP” and “microbicides,” a difference that is extremely important in the context of the rapidly changing face of HIV prevention.

Lori Heise of the London School of Hygiene and Tropical Medicine has some thoughts on this matter. “In the next few years, as policymakers, providers, and potential users are trying to get their minds around all this new research and the expanding array of prevention options” she says, “it is absolutely essential that we stick to the language of ‘oral PrEP’ and ‘microbicides’ (for instance: ‘oral tenofovir’ or ‘tenofovir gel’).”

There has been a move within scientific circles to shift the language toward PrEP and ARVs, just making distinctions between mode of delivery (topical, oral, systemic), and there are supporters of this formulation. “However, as we shift from clinical trials into introduction and use,” she says, “we need every means at our disposal to help people make appropriate distinctions among methods.”(See this Mapping Pathways blog post for a snapshot of the various ways in which antiretrovirals can be used to prevent new HIV infections.)

Clear and accurate terminology help policymakers, advocates, and other stakeholders engage in rational discussions about which methods might best suit the needs of different individuals at different moments in time and with which types of partners or sexual settings. Substituting words or using umbrella terms tends to cloud clarity and cause confusion. “Over the last several months, I have sat through a number of presentations that combine information about oral PrEP and microbicides, but use the language of PrEP to describe both.” Lori recounts. “Even among groups of experts, I have noticed people getting confused – misapplying data, conclusions, or assumptions that mostly apply to microbicides or to oral PrEP, to both.There is a tendency to talk about PrEP and topical PrEP – but people don't register the ‘topical’ and so important nuances are lost.”

Indeed, these different products have critical distinctions to keep in mind. For instance, oral PrEP may potentially protect a wider range of users than microbicides, such as in the case of injection drug users (IDUs) whose primary risk of HIV infection is from tainted syringes, not unprotected sexual intercourse (though we are still waiting on data on the efficacy of PrEP among IDUs. Then, the license to develop tenofovir gel as a microbicide is held by the public sector, while the licenses for oral tenofovir and Truvada – both of which are already available for treatment – are controlled by Gilead. This dual-use issue where ARVs taken orally can be used for either treatment or prevention doesn't exist for any microbicide.

“These distinctions are important, and I think we need to use terminology that helps people keep them in the forefront of their minds – at least for the next few years, as we broaden the circle of discussion to add groups that as yet know very little about PrEP or microbicides....In this case,” says Lori, “I think elegance must take second seat to being clear and helping people absorb vast amounts of new information.”


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

From iPrEx to TDF2: A Quick Look at the Prevention Journey this Past Year

Starting in July 2010, encouraging results from a number of HIV prevention studies have revolutionized the HIV prevention landscape over this past year – from using oral PrEP and microbicides among HIV-negative people to reduce the risk of infection, to providing early antiretroviral treatment to people with HIV to reduce the risk of transmitting the infection to their uninfected partners.

Here is a quick look at six of the most significant trials: CAPRISA 004, iPrEx, FEM-PrEP, HPTN 052, Partners, and TDF2 that, together, are radically changing the way we look at prevention.

July 2010: CAPRISA 004 – a microbicide study

Background: Conducted by the Centre for the AIDS Programme of Research in South Africa (CAPRISA), Family Health International (FHI), and CONRAD. Funded by the United States Agency for International Development (USAID) and Technology Innovation Agency (TIA).

Who: 889 sexually active women.

Where: South Africa.

What: 1% tenofovir vaginal gel, applied within 12 hours before and after sexual intercourse.

Key results: The microbicide provided 39% protection from HIV acquisition. In women who used the gel more than 80% of the time, there was 54% efficacy. The gel also halved the women’s risk of acquiring HSV-2, the virus that causes genital herpes and also increases the risk of contracting HIV.

To know more about this study, click here and here.

November 2010: iPrEx – a large-scale, Phase III PrEP study

Background:Funded by the U.S. National Institutes of Health (NIH) through a grant to the J. David Gladstone Institutes, a non-profit independent research organization affiliated with the University of California at San Francisco (UCSF). Additional funding provided by the Bill & Melinda Gates Foundation.

Who: 2,499 men who have sex with men and transgender women who have sex with men.

Where: Peru, Ecuador, South Africa, Brazil, Thailand and the US.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate), as well as monthly HIV testing and risk-reduction counseling.

Key results: PrEP provided 42-44% protection from HIV acquisition. The protective effect was even higher among those with good pill adherence. According to the initial findings, with 50% adherence reported, the efficacy was 50%; with 90% adherence reported, there was 73% efficacy. Updated findings were presented at the International AIDS Society conference in Rome: the drug had 92% efficacious in preventing HIV infection amongst those who had detectable drug levels; overall efficacy was 42%.

To know more about this study, click here and here.

April 2011: FEM-PrEP – a Phase III PrEP study

Background: Implemented by Family Health International (FHI) in partnership with research centers in Africa. Funded by the United States Agency for International Development (USAID), with early funding from the Bill & Melinda Gates Foundation.

Who: 1,951 sexually active women.

Where: Kenya, South Africa, and Tanzania.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate), as well as HIV testing and counseling.

Key results: The interim FEM‐PrEP study results were inconclusive. As determined by a preliminary data review, the study would not have been able to demonstrate whether or not Truvada was effective in preventing HIV in women in this study. FHI, therefore, decided to close the trial early due to futility.

To know more about this study, click here and here.

May 2011: HPTN 052 – a Phase III antiretroviral study

Background:Conducted by the HIV Prevention Trials Network (HPTN). Funded by the National Institute for Allergy and Infectious Diseases (NIAID) at the US National Institutes of Health (NIH). Additional support provided by the NIAID-funded Adult Clinical Trials Group.

Who: 1,763HIV serodiscordant couples, in which the HIV-infected partner had a CD4+ cell count of 350-550 cells/mm^3.

Where: Botswana, Brazil, India, Kenya, Malawi, South Africa, Thailand, United States and Zimbabwe.

What: Initiation of early antiretroviral treatment, as well as regular counseling.

Key results:The interim review showed that antiretroviral treatment reduced the risk of HIV transmission from treated partner to uninfected partner by 96%.

To know more about this study, click here and here.

July 2011: Partners – a Phase III PrEP study

Background: Funded by the Bill & Melinda Gates Foundation.  The University of Washington International Clinical Research Center is the study sponsor and coordinated the trial in collaboration with investigators at the study sites.

Who: 4,758 heterosexual African HIV serodiscordant couples, that is, in which one partner had HIV and the other did not. 

Where: Kenya and Uganda.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate) or tenofovir (oral TDF), as well as HIV testing and counseling.

Key results: The risk of infection was reduced by 73% in those who received Truvada, and by 62% in those who received tenofovir alone. Adherence was extremely high: more than 97% of doses dispensed were taken, and 95% of participants stayed in the study.

To know more about this study, click here and here.

July 2011: TDF2 – a PrEP study

Background: Conducted by BOTUSA, a partnership between the Botswana Ministry of Health and the US Centers for Disease Control and Prevention.

Who: 1,200 sexually active men and women.

Where: Botswana.

What: Once-daily does of Truvada (oral FTC-TDF – emtricitabine and tenofovirdisoproxilfumarate), as well as HIV testing and counseling.

Key results: In the primary analysis, it was seen that Truvada reduced the risk of infection by 63%. In the secondary analysis, excluding infections that occurred amongst people who had run out of their Truvada pills and had not taken one for at least 30 days, there was 78% efficacy.

To know more about this study, click here and here.

To stay abreast of research into new prevention technologies, check out AVAC and IRMA.

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

Antiretroviral prevention methods 'not in competition' with each other

Via AIDSMap, by Keith Alcorn.

Antiretroviral prevention methods are not in competition, and policy makers and providers need to start to thinking about how antiretrovirals, pre-exposure prophylaxis and microbicides will be provided as part of a combination prevention package – and who will benefit most from each method, delegates heard at a satellite meeting on the opening day of the Sixth International AIDS Society Conference (IAS 2011) in Rome.

“You don’t want to have the family planning clinic here, the pills clinic here, the injections clinic here, and the microbicides clinic over here,“ said Dr Stephen Becker of the Bill and Melinda Gates Foundation.

Delegates were discussing the rapidly changing landscape of HIV prevention methods that use antiretroviral drugs. One year ago, at the International AIDS Conference in Vienna, the world heard the results of the CAPRISA study, which showed that a microbicide gel containing tenofovir halved the risk of HIV infection in women who used the vaginal gel consistently.

Since then results from four studies have added to the array of prevention methods that exploit antiretroviral drugs to prevent transmission or acquisition of HIV infection:

• The iPrEx study showed that taking the antiretroviral combination Truvada (tenofovir and emtricitabine (also known as FTC) reduced the risk of HIV infection in men who have sex with men by 44%.
• The HPTN 052 study showed that early treatment reduced the risk of HIV transmission to an uninfected regular partner by at least 96%.
• The Partners study showed pre-exposure prophylaxis with Truvada or with tenofovir alone reduced the risk of HIV infection by between 62% and 73%.
• The TDF2 study showed that  pre-exposure prophylaxis with Truvada reduced the risk of infection by between 62% and 78%.

The first tenofovir-containing microbicide could receive regulatory approval by the end of 2013, subject to positive results from a confirmatory trial now taking place in South Africa. That study is testing exactly the same dosing regimen as that used in the CAPRISA study, the so-called BAT 24 dosing schedule: one dose Before, one After, and no more than Two doses in 24 hours.

A second CAPRISA study (008) is testing the roll-out of tenofovir gel through family planning clinics in KwaZulu-Natal, comparing the monthly testing and follow-up schedule used in the original CAPRISA study with a three-monthly schedule, in order to examine the feasibility and acceptability of providing a microbicide through existing health services that target sexually active women.

Although the South African government has already begun investing in the scale-up of production facilities to manufacture the gel, the extent of demand for the microbicide is still unclear. Studies of women’s’ attitudes towards the microbicide will be needed to gauge demand, but a lot of work will also be needed to develop demand – and to make sure that women understand how they could benefit from using the microbicide.

“We need to reach out to women who don’t perceive themselves to be at risk, and we should be getting communities to rally round to be early adopters of tenofovir gel,” said Samu Dube of the Global Campaign for MIcrobicides.

“We need to get the product to the places where women are: the family planning clinics, the immunisation centres, antenatal clinics. We also need to target the school health system.”

However, work will also be needed to convince the providers of those services that they have a role to play in expanding women’s opportunities to protect themselves from HIV infection.

Read the rest here.

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

Safety Issues in PrEP: A Public Meeting

 You are invited to a public meeting with the Forum for Collaborative HIV Research in Washington D.C.:

Safety Issues in Pre-exposure Prophylaxis for HIV negative individuals, proposals for management of safety concerns, and pending plans for scale-up

Forum for Collaborative HIV Research

1608 Rhode Island Avenue, NW

Washington, DC 20036

August 19, 2011

8:30am - 4:00pm

The Forum for Collaborative HIV Research has been tasked by our collaborators in the public health community, including the US Food and Drug Administration, to convene an open public meeting to address safety issues that may surround the introduction of biomedical approaches to prevent HIV infection. Recent data from the iPrEx, Partners PrEP and CDC’s TDF2 studies support a conclusion that pre-exposure prophylaxis (PrEP) with antiretrovirals may be effective at preventing transmission of infection in otherwise healthy, vulnerable individuals upon exposure to HIV. This important finding may lead to scale-up, broad use of PrEP and, potentially, approval of a PrEP indication.

Recently, the drug development paradigm has also shifted with more focus on safeguarding individuals on medications. Premarket studies can miss important safety signals, either because the patient population is different and limited by enrollment criteria, too small to see low incidence events, or exposure is not long enough to identify latent effects. Compensatory behavioral issues may also be a concern upon scale-up. Appropriate communication strategies to reach the intended healthcare provider and the intended vulnerable populations must be identified and formulated. Mechanisms to anticipate and/or control the development of resistant HIV are also important. Finally, public focus as a result of our meeting may identify additional public health issues that should be addressed as well.

The Forum meeting will follow our usual format of panel discussions featuring stakeholders, including academics, trialists, clinicians, community advocates, public health professionals, and others. Each will be asked by a moderator to address a set of pre-prepared questions. Four panels are planned: (1) What are the safety issues of concern with pre-exposure prophylaxis?; (2) what are potential remedies to control safety risks and their pros and cons?; (3) what are the public health implications?; and (4) finally, a panel will summarize and identify next step.

Because of limited space, public participation in the meeting room will be limited to one participant per organization. An overflow room will be available for attendees on an as-needed basis. The meeting will be webcast to enhance national dissemination. Written supplementary questions can be directed to the panels. Webcast attendees can also submit written questions via instant messaging.

Registration: Register online at http://prep-reg.com/ to attend the public meeting or to view the live webcast.

Location: 1608 Rhode Island Avenue NW, Washington, DC 20036
Date and Time: August 19, 2011 8:30 AM-4:00 PM

________________________________________
Forum Announcements

Studies show new progress in HIV testing in emergency departments

July 29

A CDC sponsored supplement released in the Annals of Emergency Medicine details new HIV testing efforts in Emergency Departments. "Emergency departments play a critical role in helping people learn their HIV status, connecting them to life-prolonging care, and helping them avoid transmitting the virus to others"said Jonathan Mermin, MD, Director of CDC's Division of HIV/AIDS Prevention. Click here to read more

Controlling the HIV Epidemic - The Promise of ARV-Based Prevention: Presentations now available

July 28

Presentations made at the Forum co-sponsored IAS Satellite Symposium "Controlling the HIV Epidemic - The Promise of ARV-Based Prevention" are now available. Click here to read more

Statistical Methods for Causal Inference in Observational and Randomized Studies: Course fees increase on August 1

7/26/11 This course concerns statistical methods for causal inference using observational and experimental longitudinal data. The course will focus on the application of methodological advances in statistical and causal research to improve the design and interpretation of safety analyses. These analyses will become increasingly important in the post-marketing safety environment for new drugs.

Dates: September 26-28, 2011.
Location: UC Washington Center, Washington, DC.

To register, please use the following link: www.hivforum.org/stats2011

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

Treatment As Prevention: We Urgently Need Policy Guidance

Via PLoS, by Nathan Ford.

The International AIDS Society conference on HIV Pathogenesis, Treatment and Prevention in Rome has been hailed as a landmark conference for HIV prevention. Just as the AIDS conference in Vancouver in 1996 marked the beginning of the international effort to roll out antiretroviral therapy globally, so Rome will likely be remembered as the beginning of a new era in biomedical prevention.

The results of the HTPN 052 discordant couples trial, which found the greatest incidence reduction of any prevention intervention evaluated to date, were met with a standing ovation. This trial found a 96% reduction in HIV transmission and a 40% reduction in serious complications, in particular tuberculosis (TB), among patients starting ART early, at CD4 350-550 cells/mm³.

Implementation of this strategy is, however, hampered by lack of guidance from the World Health Organization. Draft guidelines for the provision of ART in discordant couples have been in process for many months, and their release was first announced in May, and then again July. However, by the end of the conference it remained unclear when the guidelines would be released, or what they would say.
Rumours spread in the conference corridors that WHO had been pressured to delay the release. Some suggested the issue at stake was to find the right balance in investment between the results of HTPN 052 and those of the recently completed pre-exposure prophylaxis trials that also reported a substantial prevention benefit.

There are at least three reasons why such a trade off is wrong.

First, providing ART earlier is desirable for more reasons than reduced HIV transmission: the HIV-positive individual receives treatment at a stage in their disease that developed country guidelines already consider therapeutically beneficial; their risk of developing incident diseases, in particular TB, is substantially reduced; reducing TB incidences confers the additional public health benefit of reducing the risk of TB transmission.

Second, discussions about whether to give ART to HIV-positive or HIV-negative individuals are ethically problematic. Economics has long been described as the ‘dismal science’, but it is hard to think of a more dismal economic proposition than to delay giving ART to people already infected with the pathogenic HIV virus in order to give the drugs to HIV-negative individuals instead.

Third, there are fundamental practical differences to the two approaches. Implementing the results of HTPN 052 means further extending what is already happening (giving ART to HIV-infected individuals); in contrast, giving ART to HIV-negative, at-risk individuals requires extensive operational research to help define what is essentially an entirely new programmatic approach.

Read the rest here.

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

From 'what if' to 'what now': implementing the new prevention technologies

Via AIDSMap, by Gus Cairns.

 

Two consecutive sessions at the sixth International AIDS Society conference in Rome yesterday were devoted, now we have convincing scientific data on the benefits of treatment as prevention and PrEP, to putting these new prevention methods into practice.

“We have moved from ‘What if?’ to ‘What now?’” was the comment of Mitchell Warren, Executive Director of the AIDS Vaccine Advocacy Coalition (AVAC), on what else we need to know, what barriers need to be addressed , and what resources might be required, to maximise the promise of antiretroviral-based prevention.

Anthony Fauci, Director of the US National Institute of Allergies and Infectious Diseases (NIAID), said: “We now have a solid scientific foundation to say that even in the absence of a vaccine we have the capacity to end the epidemic. I can’t go to the US President and say: 'We can cure HIV.’ But I can say ‘Ending the epidemic is scientifically doable’.”

Earlier, however, Nancy Padian from the Office of the US Global AIDS Coordinator had outlined formidable challenges still to be answered if antiretroviral treatment could bring about this goal.

She said that questions still needing answers include whether antiretroviral drugs (ARVs) really are a durable and reliable means of viral load suppression over a period of years and whether increasing the proportion of people on treatment would lead to increased levels of resistance. The biggest practical question, however, was whether treatment as prevention would work in situations where a high proportion of transmissions came from people with acute, recent HIV infections.

The biggest barriers to treatment as prevention, however, are stigma and lack of resources. Implementing ARV-based prevention would not only be expensive in terms of drugs; it would require added human resources and increased training and task-shifting for prevention counsellors so they can deal with biomedical data. There would also be added costs in terms of tests and monitoring.

The other big barrier will be the stigma of being tested, she said, particularly for at-risk populations in societies where injecting drug use, male-male sex, or sex work were criminalised and stigmatised. Treatment as prevention would require people not simply to test and then go to more supportive community organisations for prevention advice; it required a much closer relationship with medical personnel who might be prejudiced or feared to be so.

Mitchell Warren issued a call to action to implement the new strategies, but his presentation was tempered by realism. “We have evidence, we have data, and we now need to make decisions,” he said.

Read the rest here

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

How Sexy Sex Can Help Prevent HIV Transmission

Last month, a special supplement of Health Research Policy and Systems featured an article written by Anne Philpott and Wendy Knerr of The Pleasure Project. The write-up, ‘Strange bedfellows: bridging the worlds of academia, public health and the sex industry to improve sexual health outcomes’, discusses the public health community’s approach to HIV prevention, which is mostly focused on disease and the negative outcomes of sex. The authors make a case for an alternative approach based on the positive, liberating and pleasurable aspects of safer sex. The Pleasure Project, a largely volunteer-run organisation based in India and the UK, is a programme that adopts exactly such an approach. Their tagline says it best: ‘Putting the sexy back into safer sex’.

Mapping Pathways checked in with Anne Philpott to get her thoughts on how such an approach can help prevent HIV. “We believe you can have safer sex if you know how to have good sex. Pleasure is the primary reason people have sex” explains Anne, “yet it is almost completely absent in the public health domain – in programming, education and research. Since HIV is spread mainly through sexual transmission, efforts to prevent HIV need to consider the role that sexual pleasure and desire play in sexual behaviour.”

Anne’s personal ‘light-bulb moment’ took place at a microbicides session during an HIV/AIDS conference. “The speaker kept using terms like ‘insertive probe’ and ‘receptive cavity’, and for the longest time I thought he was discussing the technical cellular dynamics of microbicides or something like that. Turned out he was trying to talk about penetrative sex – for me, that was a moment of total frustration with the public health world. Why can’t we just say ‘penis’ and ‘vagina’?”

The Pleasure Project carries out advocacy about the importance of pleasure in sexual health, trains health professionals and educators about the eroticisation of safer sex, conducts research to build the evidence base, and pushes for safer sex in the erotic media industry. It sees itself as a bridging organisation – bringing pleasure into the world of public health and bringing public health into the world of pleasure – and works to make sure that the lessons are learned across the two different worlds.

What is one of the key lessons for the public health community? “Sex sells. People in the commercial world use sex to sell things like cars, toothpaste, pens…almost anything! Why not use sex to sell safer sex?” says Anne. “While working at a firm that made female condoms, I noticed how women would bring up the positive elements of the condom and how it actually increases sexual pleasure. We need to focus on things like that along with conveying the message of protection. That’s what will help motivate more and more people to practice safe sex – fear tactics only work up to a point.”

The Female Health Company, which manufactures markets and sells female condoms, seems to agree wholeheartedly. The company has provided key support to organisations advocating for a more positive, pleasure-focused approach to the female condom. “The innovative approach of eroticising the female condom is already having an impact,” says Robbie Nelson, the company’s programme and sales director. “The NGOs we work with, which have had pleasure trainings from The Pleasure Project, are not only making it easier for people to talk about condoms, but they are showing people how sex can be fun with condoms.”

The Pleasure Project’s strategy certainly seems to be working: Their website gets more than 5,000 unique visitors each month – interestingly enough, there’s been a recent surge in hits from Turkey and countries in the Middle East. The Global Mapping of Pleasure (‘A directory of organizations, programmes, media and people who eroticize safer sex’) has been downloaded more than 20,000 times. The organisation is now also pushing for greater research into the pleasure potential of new HIV-prevention products like microbicides. Numerous other initiatives, such as LifeLube, are also attempting to combine the idea of pleasure with HIV prevention. Together, these organisations may kickstart something of a sexual revolution in the public health community’s efforts to combat HIV.

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

Extension of iPrEX HIV PrEP Study Begins at 11 Sites in 6 Countries

Via iPrEX News.

The iPrEx Open-Label Extension Study (iPrEx OLE), the next phase of the first human study to report efficacy results on pre-exposure prophylaxis (PrEP) to prevent HIV infection, has begun at clinical trial sites around the world. Approximately 2,000 men and transgender women who have sex with men are expected to participate in the 72-week iPrEx OLE study. Study sites in the United States and South Africa are enrolling participants now, as other study sites finalize the regulatory approval process.

In PrEP, antiretroviral medications that are usually used to treat HIV are taken by uninfected people to reduce their risk of infection. The iPrEx study found that men and transgender women who have sex with men (MSM) who took a single daily tablet containing the HIV medications emtricitabine and tenofovir (FTC/TDF), known commercially as Truvada®, experienced an average of 44% fewer HIV infections than those who received a placebo (blank pill). HIV infection rates in the iPrEx study dropped by 90% among those who used PrEP consistently enough to have detectable drug in the body. The HIV risk reduction benefits of PrEP were in addition to those provided by safer sex counseling, condoms, HIV testing and the detection and treatment of sexually transmitted infections. iPrEx study results were published in the New England Journal of Medicine in November, 2010.

The news of the start of iPrEx OLE follows the announcements by two other major PrEP studies, Partners PrEP and the CDC study in Botswana, known as TDF2, which demonstrated the safety and efficacy of PrEP in heterosexual women and men.

AdvertisementiPrEx OLE is a continuation of the iPrEx study that will collect additional data on PrEP efficacy, safety and adherence. All HIV-negative participants who took part in the original iPrEx study and who wish to participate will receive FTC/TDF for HIV prevention for 72 weeks through iPrEx OLE. No placebo will be used in the Open Label Extension.

"We are in a critical moment in HIV prevention research," said iPrEx Protocol Chair Robert Grant, MD, MPH of the Gladstone Institutes and the University of California at San Francisco. "iPrEx provided the first proof of an important new method of HIV prevention that can help slow the global toll of 2.6 million new HIV infections each year. Partners PrEP and the TDF2 study have now expanded that finding by demonstrating the effectiveness of PrEP in heterosexual women and men. Developing and deploying proven HIV prevention methods -- including PrEP, microbicides, vaginal gels, clean needles, medical male circumcision, early treatment, counseling, testing, condoms and suppressive therapy for pregnant women will all be key to slowing the global epidemic."

Read the rest here.

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

In Conversation with Joe Romano

Joseph Romano, Ph.D., has been involved in HIV/AIDS research and development for 20 years. In the last decade, he has focused on the development of HIV microbicides. We checked in with Joseph to get his thoughts on a number of things: the microbicide pipeline, the recent HPTN 052 results, clinical trials and the hardest part about his job.

MP: How would you characterize the state of the microbicide pipeline? Right now, the main focus seems to be on ARV-based products. Is there a chance that we may see some non-ARV-based microbicide products in the near future?

JR: The current focus on ARV-based products is the result of some earlier failures with non-ARV microbicide products, and the lack of a robust set of other options to develop. ARVs are very potent and very specific inhibitors of HIV infection, and recent studies have shown that vaginal gels containing an ARV (tenofovir) as well as oral use of ARV pills (Truvada) can prevent transmission of HIV in specific populations. It is likely that these positive results will fuel the development of additional ARV-based microbicide products in the foreseeable future.

However, there remains a need for something other than ARVs. One of the concerns with ARV-based microbicides is over the issue of resistance. In situations where someone is HIV positive and unaware of their status, the use of a microbicide product could lead to the selection of resistance in this person, and that could compromise the ability to treat this person in the future with same class of ARV therapeutics.  This is why large efficacy studies involving ARV-based prevention products are typically conducted with a great deal of HIV testing, and are also accompanied by seroconverter trials to study HIV infections that do occur in participants during microbicide trials. Another issue with ARVs is that they are very specific and are typically only active against HIV. Compounds that afford a wider spectrum of protection against other STIs would be more desirable.

There are a number of groups working on things like plant lectins and natural defence molecules that are part of the innate immune system. There are also groups exploring herbal products or extracts from such products. These alternative products are typically not as potent as ARVs and are mostly in very early stages of investigation and development.

MP: What are your thoughts on the preliminary findings from the HPTN 052 study? 

JR: The level of efficacy seen in the HPTN052 study is stunning, and is extremely important on several fronts. First, in terms of the potential of this strategy to reduce transmission, it is clearly an effective option. The study also established the benefits to infected individuals of employing treatment regimens to HIV-positive people with the inclusion parameters used for the trial.

Of course, there are some issues associated with this strategy as well. Proper product adherence over the long term will be necessary, and this is typically a challenge. Rollout of this strategy will also present challenges, in terms of cost and with regard to capacity to properly administer care.  It is possible that these results will also raise questions on the value of providing drugs to infected individuals as per HPTN 052, versus distribution of drugs to uninfected populations as per an oral PrEP strategy.

However, in terms of the results themselves, this is an extremely important outcome which will likely have significant ramifications going forward.  It will be important to remember that despite these findings, the development of other prevention strategies for HIV-negative people will remain an important priority.

MP: What issues are you most concerned about at the moment? 

JR: I have two concerns regarding microbicides and HIV prevention product strategies. First, a clear lesson from recent (as well as earlier) clinical trials is that product adherence remains a major challenge to the field. Trial participant compliance with product use directions is difficult to achieve, and perhaps even more difficult to measure. Thus, the dependence of these strategies on proper compliance with product use by trial participants (as well as populations receiving access to such products after approval) will always present a challenge to achieving adequate efficacy. There needs to be some innovative thinking and development with regard to achieving higher and consistent rates of proper product adherence. Novel drug delivery technologies and strategies that reduce the dependence on users to bear the burden of compliance are essential. Innovative ways to measure product adherence accurately must also be developed in order to achieve proper evaluation of products in clinical trials.

My second concern is with regard to efficacy trial strategies in the post-placebo control era.  It will not be feasible from a cost or capacity perspective to run multiple non-inferiority studies with HIV prevention products.  Innovative trial design as well as the development of robust surrogates for efficacy will be crucial for the field going forward.

MP: What is the hardest part about your job?

JR: There are two things: The slow pace and high failure rate that are inherent in the drug development process, and the effects of resource constraints on good science. Neither of these is specific to microbicides or HIV prevention – unfortunately they are a part of drug development in any setting.

Joseph Romano, Ph.D., is President at the NWJ Group, LLC. He provides strategic and operational consulting in the fields of pharmaceutical and biotechnology, with expertise in drug, vaccine, device and diagnostics development.


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