VOICE Lesson: It's Unfair to be Non-Adherent

This post by IRMA's Jim Pickett first appeared on the blog of the HIV Prevention Justice Alliance.


The VOICE results are extremely important to the field of new prevention technology research. I hope current/future/much-needed discussions about VOICE don’t get drowned out by the HYPE (yes, all caps HYPE) surrounding the “baby cure” story which has dominated coverage out of CROI so far.

If there is one VOICE lesson to focus on, it is adherence. Or in this case, the upsetting lack thereof. It is absolutely important to fully understand why so many of the women in the trial didn’t apply the gel, or take the pill. And it is critically important for scientists to develop things people actually WANT to use, and DESIRE. Perhaps a daily gel, or a daily pill, is simply not desirable for a lot of folks. Makes sense to me.

But here’s the rub. The field can’t move forward with product development when people don’t actually test-drive the product being investigated. Products can’t be improved without data from people who actually used the product. Sure, a daily gel or a daily pill may not be everyone’s idea of a good time… but the only way those ideas get translated from the clunky Model T Ford to a slick 2013 BMW is through a long, iterative process. Which requires trial participants to APPLY THE GEL and/or TAKE THE PILL.

I get that people join trials for all kinds of reasons, and that for many; it is their only access to healthcare. So, they may have no interest in actually participating in test driving anything, but are very excited about regular HIV and STD screening, counseling, access to condoms and lube, referrals to other services, etc. Can’t be mad at them for wanting those things. Right?

It’s a crime, really, or at the very least an outrage, that clinical trials end up being the only healthcare access point for too many folks. That needs to be addressed, on its own.

But…we simply can’t afford enrolling thousands of people into complicated and costly clinical trials to have them just forgo what they SIGNED UP to do. Let’s be brutally honest here, joining a trial to get health screenings and condoms is great for the individual – but it does NADA, NOTHING, NOOTCH for the community/communities fighting HIV who are desperate for new tools to prevent HIV.

Being in a clinical trial is a commitment to following the protocol as best as possible, and being honest when unable. Clinical trial participation necessitates a strong sense of altruism, a desire to help answer big questions for whole populations. I think it is unfair to everyone, especially highly impacted communities where HIV rates are soaring, and where the crisis is anything but over, for trial participants to sign informed consents and derive individual benefits from trials without fully engaging in the study protocols that would allow for potential population benefits.

There are not unlimited resources. In fact, they are shrinking (Hello Sequester!) We can’t continue to fund expensive, resource-intensive, multi-year trials in which most people only SAY they test drove the product.

Jim Pickett is the Chair of the International Rectal Microbicide Advocates (IRMA). This blogpost is part of our ongoing coverage of the 2013 Conference on Retroviruses & Opportunistic Infections (CROI). To read more perspective and analysis on the VOICE results at CROI, click here.

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  *Join IRMA's robust, highly-active. moderated, global listserv addressing rectal microbicide research and advocacy as well as other interesting new HIV prevention technologies by contacting us at rectalmicro@gmail.com. Joining our listserv automatically makes you a member of IRMA - a network of more than 1,100 advocates, scientists, policy makers and funders from all over the world.

*Please look for us on Facebook: www.facebook.com/InternationalRectalMicrobicideAdvocates, and you can follow us on Twitter: @rectalmicro.

*Also, please note that shared news items from other sources posted on this blog do not necessarily mean IRMA has taken any position on the article's content.

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IRMA Statement on VOICE Results

[Click here for the VOICE press release - "Daily HIV Prevention Approaches Didn’t Work for African Women in the VOICE Study" - from the Microbcide Trials Network]


IRMA, like the rest of new prevention technology researchers and advocates, is disappointed to learn that daily oral Truvada was not found to be an effective HIV intervention among the African women at risk for HIV who participated in the VOICE trial.

We applaud the efforts of the 5,029 women from South Africa, Zimbabwe, and Uganda who volunteered to participate in the VOICE trial. We also commend the Microbicide Trials Network and the National Institutes of Health for successfully executing this extraordinarily ambitious, important trial, and for contributing critical new information to the field.

Today at CROI 2013 we learned that the majority of women in the daily oral Truvada arm of VOICE were not taking their drugs regularly if at all. Rather than a biological explanation, it appears daily oral Truvada was not effective at preventing HIV among the women in the VOICE trial because the drug was not used regularly.

The results of VOICE indicate low adherence to all the drugs/regimens tested in the trial. There was also low adherence in the daily oral tenofovir and daily tenofovir gel arms. Both these arms were closed due to futility in late 2011 after separate reviews by the independent Data Safety and Monitoring Board. VOICE’s daily oral Truvada arm remained open until August 2012.

One of the biggest challenges the field faces is that of adherence. Clinical trials cannot show that a drug works to prevent HIV if trial participants do not take the drug. More must be done to accurately assess adherence during clinical trials in “real time”, and more must be done to develop HIV prevention interventions that people actually want to use, and like to use. But, we won’t be able to refine the drugs, the drug dosing strategies, and/or the drug delivery vehicles to make them more acceptable if trial participants are not adherent along the way.

Science is an iterative process. We are in the “car phone” phase of new prevention technologies - some of the drugs and dosing strategies are perhaps a little clunky. We all want to get to the “i-Phone” phase where we have interventions that are highly acceptable, and desired, but we won’t get there without going through the clunky phase first.

As the field moves forward, issues of recruitment are as important as adherence. Identifying potential trial participants who are most likely to be adherent during the trial is absolutely critical – and very challenging, as the way to achieve this is admittedly not clear.

The MTN-017 trial, a Phase II safety and acceptability study testing a reduced glycerin formulation of tenofovir gel, is getting ready to launch in the coming months. The study will enroll 186 gay men and transgender women at sites in Thailand, South Africa, Peru, and the United States, including Puerto Rico. It will be absolutely essential that MTN-017 volunteers take the study drugs as directed. If adherence is low during this trial, adequate amounts of safety data will not be collected, making it likely that efforts to develop tenofovir gel as a rectal microbicide will be halted permanently. Have no doubt, this would be a huge setback for rectal microbicide research, development, and advocacy efforts in general.

IRMA is very supportive of MTN-017’s inclusion of “real time” monitoring to assess adherence throughout the trial. This will allow investigators to understand and address challenges regarding adherence while the trial is underway, and will help participants make appropriate adjustments in “real time” to improve adherence outcomes. MTN-017 sites should also pay extra special attention to recruitment activities and work to engage and enroll individuals who are most likely to fully participate in the trial, and follow the various regimens being tested as directed.

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*Join IRMA's robust, highly-active. moderated, global listserv addressing rectal microbicide research and advocacy as well as other interesting new HIV prevention technologies by contacting us at rectalmicro@gmail.com. Joining our listserv automatically makes you a member of IRMA - a network of more than 1,100 advocates, scientists, policy makers and funders from all over the world.

*Please look for us on Facebook: www.facebook.com/InternationalRectalMicrobicideAdvocates, and you can follow us on Twitter: @rectalmicro.

*Also, please note that shared news items from other sources posted on this blog do not necessarily mean IRMA has taken any position on the article's content.

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[Project ARM] GLAM Lube Distribution Survey

via Survey Monkey, for [Project ARM] GLAM Lube Distribution Survey

Thank you for taking a few minutes to complete this survey on lubricant distribution in your country.

International Rectal Microbicide Advocates (IRMA) has launched a special initiative called "Project ARM - Africa for Rectal Microbicides" to ensure rectal microbicide research and advocacy are on the African map.

The top priority of Project ARM is lube access for people who engage in anal intercourse.

Condoms and safe, condom-compatible lubricant should be used during anal intercourse to provide protection against HIV and other STDs. Safe, condom-compatible lubricants are also used by many women who desire extra lubrication during vaginal intercourse. Condoms used without proper lubricant can break.

With partners amfAR and AVAC, Project ARM has developed the GLAM campaign (Global Lube Access Mobilisation) in an effort to improve access to safe, condom-compatible lubes for individuals in Africa and other countries where lube access is poor.

Your answers to these questions will inform a "tool kit" that is being developed to support lube access advocacy and implementation.

Access the survey here.


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*Join IRMA's robust, highly-active. moderated, global listserv addressing rectal microbicide research and advocacy as well as other interesting new HIV prevention technologies by contacting us at rectalmicro@gmail.com. Joining our listserv automatically makes you a member of IRMA - a network of more than 1,100 advocates, scientists, policy makers and funders from all over the world.

*Please look for us on Facebook: www.facebook.com/InternationalRectalMicrobicideAdvocates, and you can follow us on Twitter: @rectalmicro.

*Also, please note that shared news items from other sources posted on this blog do not necessarily mean IRMA has taken any position on the article's content.
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Rectal Microbicides Open New Frontier in HIV Fight

 [Citizen News Service and IRMA are collaborating to amplify rectal microbicide research and advocacy, as well as IRMA-led initiatives, throughout AIDS 2012.]

via Citizen New Service, by  Chief K.Masimba Biriwasha

 Microbicide research has gained momentum in recent years with focus largely on products to prevent HIV during vaginal sex. However, there is a growing momentum to develop rectal microbicides for women, men, and transgender individuals around the world who engage in anal intercourse. Microbicides are products (currently under research) designed to prevent or reduce the sexual transmission of HIV or other sexually transmitted infections when applied inside the vagina or rectum. Most vaginal microbicides are being tested as gels or rings, while rectal microbicides are primarily being tested as gels.

According to the International Rectal Microbicides Advocates (IRMA), rectal microbicides are products – that could take the form of gels or lubricants – being developed and tested to reduce a person’s risk of HIV or other sexually transmitted infections from anal sex. In spite of the public health need for rectal microbicide research, there is serious institutional, socio-cultural and political stigma around the issue.

Click here to read the rest.


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*Join IRMA's robust, highly-active. moderated, global listserv addressing rectal microbicide research and advocacy as well as other interesting new HIV prevention technologies by contacting us at rectalmicro@gmail.com. Joining our listserv automatically makes you a member of IRMA - a network of more than 1,100 advocates, scientists, policy makers and funders from all over the world.

*Please look for us on Facebook: www.facebook.com/InternationalRectalMicrobicideAdvocates, and you can follow us on Twitter: @rectalmicro.

*Also, please note that shared news items from other sources posted on this blog do not necessarily mean IRMA has taken any position on the article's content.
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Reformulation of Tenofovir Vaginal Gel Safe for Rectal Use

via Eurekalert.org

A change in the formulation of tenofovir gel, an anti-HIV gel developed for vaginal use, may make it safer to use in the rectum, suggests a study published online this week in the Journal of Antimicrobial Chemotherapy. In laboratory tests of rectal tissue, researchers from the Microbicide Trials Network (MTN) found that the reformulated gel was less harmful to the lining of the rectum than the original vaginal formulation, and just as effective in protecting cells against HIV.

"The lining of the rectum is much more fragile than the vaginal epithelium, so we can't be certain a product like tenofovir gel that is safe for vaginal use will be completely safe to use in the rectum," said lead study author Charlene Dezzutti, Ph.D., associate professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and principal investigator of the MTN Network Laboratory. "We are very encouraged by our laboratory data that suggest the reformulated gel could be safer for rectal use, and serve as a dual compartment gel for use in both the vagina and rectum."

Tenofovir gel has shown some promise in reducing HIV risk in women through vaginal sex. But because the rectal epithelium – the lining of the rectum that serves as the first line of defense against HIV – is much thinner than the vaginal lining, the gel may not be safe or effective to use rectally. Indeed, unprotected anal sex is 10 to 20 times more likely to result in HIV infection than unprotected vaginal intercourse. By its nature, tenofovir gel is hyperosmolar – contains a higher concentration of sugars and salts relative to cells. This quality could have a harmful effect on the rectal lining by causing epithelial cells to shrink as they purge water to achieve balance. Weakened in this manner, the rectal epithelium may be less able to protect against HIV.

To make tenofovir gel safe and more amenable to rectal use, researchers from CONRAD, a research organization which holds the rights to develop the gel, reformulated it with a reduced amount of glycerin, a common additive found in many gel-like products. In laboratory tests conducted by MTN researchers, the reformulated gel was three times less likely to cause cells in rectal tissue to release water, and equally effective against HIV as the vaginal formulation.

Data from an early phase clinical trial of the reduced glycerin gel presented in March 2012 at the 19th Conference on Retroviruses and Opportunistic Infections (CROI), suggested it was safe and acceptable in 65 HIV-negative men and women who used it rectally once a day for one week. Results from this study, called MTN-007, and future studies will have important implications for the development of a rectal microbicide that could help protect against HIV or other sexually transmitted infections during anal sex.


Read the Rest.


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*Join IRMA's robust, highly-active. moderated, global listserv addressing rectal microbicide research and advocacy as well as other interesting new HIV prevention technologies by contacting us at rectalmicro@gmail.com. Joining our listserv automatically makes you a member of IRMA - a network of more than 1,100 advocates, scientists, policy makers and funders from all over the world.

*Also, please note that shared news items from other sources posted on this blog do not necessarily mean IRMA has taken any position on the article's content.

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Rosie the Riveter Can No Longer Represent the Face of Microbicide Research: Lessons from M2012

by IRMA member Morenike Ukpong

Rosie the Riveter is a cultural icon of the United States, representing the American women who worked in factories during World War II, many of whom produced munitions and war supplies. These women sometimes took entirely new jobs replacing the male workers who were in the military. Rosie the Riveter is commonly used as a symbol of feminism and women’s empowerment. Rosie’s picture came to represent the objective of microbicide research – an empowering tool that will enable women to have a HIV prevention option they could control, in their hand.

The microbicide research movement was actually initiated as a women empowerment movement. Women asked for a tool that they can control independently to help reduce their own risk of HIV infection. Women activists led by Lori Heise, started making a case for a women controlled option for HIV prevention. This movement was in response to a call made by an African woman on the need to have something to protect herself, Lori Heise often recalls. The earliest movement was focused on the development of a vagina application that could ensure women can use the product discretely if and when they choose too.

Trials in many African countries continue to suggest that discrete use of a microbicide may not be feasible – male involvement in the implementation of microbicide trials and its use by women engaged in the trials is important so as to ensure participant retention and prevent other potential social harm. However, Mitzy Gafos in her presentation titled ‘What have men got to do with it: the role of men in reproductive and sexual health in a predominantly rural are of KwaZulu-Natal, South Africa’ showed that women in South African can actually take decision about the use of the microbicide independent of their male partners. I would want to assume that this is the same in South West Nigeria where women are quite independent and are better able to negotiate the use of condom with their male sex partners.

With increasing discussion on anal sex and rectal microbicide, the objective of developing a microbicide seems to have shifted. It is less so about developing a tool that will empower women to have control over her sexual and reproductive health in a way that will enable her protect herself from HIV infection. More and more attention is being paid to public health needs that are larger than women focused issue.

Rosie the Riveter can no longer represent the face of microbicide research. Current research is looking at bioavailability of microbicide gel in the rectum and vagina and its efficacy in preventing HIV infection in both the vagina and the rectum at the best. This means a microbicide product can be used by men, women and transgenders.

The message about microbicide is no longer one of empowering women in Africa. The message is now about health and access to health product in African. Structural issues that will facilitate the uptake and use of microbicides are being discussed everyday. This includes the need to strengthen health systems so as to ensure product access, human right issues so as to ensure access by MSMs. The peculiar issues related to women, women access, women empowerment, has quietly fallen off the table. The events at the M2012 make this very clear.

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*Join IRMA's robust, highly-active. moderated, global listserv addressing rectal microbicide research and advocacy as well as other interesting new HIV prevention technologies by contacting us at rectalmicro@gmail.com. Joining our listserv automatically makes you a member of IRMA - a network of more than 1,100 advocates, scientists, policy makers and funders from all over the world.

*Also, please note that shared news items from other sources posted on this blog do not necessarily mean IRMA has taken any position on the article's content.

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Studies Search for "User Friendly" Microbicides for HIV Prevention

via Voice of America, by Joe DeCapua

In 2009, researchers completed a study that showed a microbicide gel could protect women from HIV infection. The gel, known as CAPRISA 004, was nearly 40 percent effective in reducing the risk of infection during sex. The encouraging findings have led to follow-up studies. But just because a microbicide can block HIV, does not mean that women will use it.

Top ranking health officials called the CAPRISA 004 study historic. They said it showed that a microbicide could empower women to protect themselves from HIV/AIDS. It was something they could use without asking a man’s permission. But would women use it outside of a clinical trial?

That’s what a U.S.-funded study called Project LINK is trying to find out. Dr. Kathleen Morrow is leading a team of researchers at The Miriam Hospital in Providence, Rhode Island.

“It’s actually the first study to my knowledge to link those physical, chemical and rheological properties and performance characteristics of a gel to the user experience - the actual sensory perceptions and experiences of the person using the product,” she said.

Not all gels are alike

Morrow is a staff psychologist at The Miriam Hospital and associate professor of psychiatry and human behavior at the Warren Alpert medical school at Brown University. Morrow and her team are not studying whether the microbicide actually works. Instead, they want to know how women react to the gels themselves.

“If my clinical counterparts, who are actually developing the pharmaceutical sides of things – the drug side of things – the drug that they will actually put into the gel or ring or whatever they’re going to put it into – if they do that and they do that well, and we have a product that will actually reduce HIV infections, the reality is it will only do that if people use it. So if people don’t use it, it will sit on a shelf and will have no impact on the HIV pandemic,” she said.

Read the Rest.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Research on Douching Reveals Little Association to Sexually Transmitted Infections

via AIDSmap.com, by Gus Cairns

Neither rectal douching nor vaginal washing appear to be as significantly associated with sexually transmitted infections as had been feared, the International Microbicides Conference in Sydney heard yesterday.

In the case of women, vaginal washing and other vaginal health practices have been associated with bacterial vaginosis (BV), an imbalance in the types of bacteria that colonise the mucous surfaces of the vagina. BV can cause pelvic inflammatory disease and premature delivery in pregnant women and is associated with a higher risk of both acquiring and transmitting HIV.

The HPTN 035 trial of the candidate microbicide PRO2000 therefore included a survey of vaginal health practices, counselling against ones associated with a raised risk of BV, and assessing any link between these practices and BV. It found none, though a smaller study of women in Los Angeles did find an association not with douching and BV, but between the use of petroleum jelly as a lubricant and BV.

In the case of rectal douching in women and gay men, there is very little we currently know about the practice. However, findings over the last couple of years that the use of lubricants for anal sex, particularly water-based ones, is associated with higher rates of sexually transmitted infections have raised concerns that other practices that impact on the fragile rectal mucosa may also raise the risk of sexually transmitted infections (STIs) and HIV. International Rectal Microbicide Advocates (IRMA) have therefore conducted a survey of rectal douching practice. Interim results were presented yesterday and the survey is still ongoing.

Vaginal and rectal practices in women in HPTN 035 and in Los Angeles

In HPTN 035, vaginal hygiene practices were assessed at quarterly visits and the 3087 participants were counselled to try not to use the practices. They were divided into women who did not practise vaginal washing, ones who only used water and ones who used other products such as soap and water or commercial douches (Kasaro).

The proportion of women not practising any vaginal hygiene fell from 60% at baseline to 36.5% at last visit, and this was a steady fall over time, not just occurring immediately after the baseline visit.
Bacterial vaginosis (BV) was common at baseline and the proportion of women with it did not change over time – at any visit 36 to 38% of women had BV. There was no association between vaginal hygiene practices and BV.

Another study of women in Los Angeles (Brown) assessed vaginal hygiene and lubricant practices in an observational cohort of 141 women. The cohort was structured to reflect a mix of ethnicity and HIV serostatus: 26% had HIV and 40% were black, 34% white and 26% Latina. Their median age was 33 (range 18-65).

Read the Rest.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Acceptability of coitally-associated versus daily use of 1% tenofovir vaginal gel among women in Pune, India

via International Health, by Sanjay Mehendale, Swapna Deshpande, Rewa Kohli, Sharon Tsui, Elizabeth Tolley

Abstract

This study reports on the acceptability of 1% tenofovir microbicide gel among participants randomised to the coitally-associated use (n=50) or daily use (n=50) arms of a Phase II clinical trial in Pune, India. In a 6-month follow-up study, information on behavioural domains was collected on a 6-point Likert scale and gel acceptability was measured on a 5-point Likert scale. Random intercept logistic modelling was performed to examine the simultaneous effects of study arm, follow-up time, sociodemographic factors and behavioural domains on gel acceptability. The mean age of female participants was 32.7 years. Women in both study arms had similar sociodemographic profiles. Women liked features such as easy use of the gel and its protective effect against HIV. Messiness was the most disliked feature. Gel acceptability increased during subsequent follow-up visits in both arms, especially in the coitally-associated use arm. Non-acceptability of the gel was almost two and a half times higher in daily users (adjusted odds ratio 2.55, 95% CI 1.18–5.51; p=0.017). Acceptability differed significantly between the two study arms at 2 months (68% vs 40%; p=0.006) and 6 months (64% vs 46%; p=0.07). Acceptability was significantly lower in those participants who reported ‘messiness’ as the most disliked feature (odds ratio 2.42, 95% CI 1.02–5.72; p=0.045). In conclusion, microbicides were more acceptable in coitally-associated users than in daily users. Leakage was a problem that requires attention. Positioning of the product in a setting such as India where the majority of decision-making is done by men would need extensive and systematic education of men.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Microbicides 2012 Conference Now Open for Registration!

M2012 Registration is Open!

"To share in the latest developments in HIV prevention through microbicides and other technologies, this is the conference to attend. The conference is the key event in the microbicides world, where cutting edge research will be presented by world experts, and you will have a chance to interact with people involved at every level of microbicides development "

-Professor John Kaldor, The Kirby Institute and Conference co-Chair

Come to Sydney in April for the 2012 International Microbicides Conference - 'From Discovery to Delivery', with state of the art plenary lectures on microbicides and other aspects of HIV prevention research, cross-disciplinary symposia, oral abstracts, and poster sessions.

M2012 will be a global forum for the presentation and discussion of the latest information on microbicides and oral pre-exposure prophylaxis for HIV prevention and their interface with other prevention strategies. There will be a strong emphasis on the role of community in both research and implementation of scientific findings. The conference is interdisciplinary, and will include basic science, pharmacokinetics, formulation and delivery, clinical research, public health, prevention science, and social and behavioural research.

WHY SHOULD YOU COME?
1. LEARN... From experts from around the world who will speak on key issues in HIV prevention technologies.
2. NETWORK... with a cross-disciplinary group of researchers, community representatives and policy makers, to support you in applying new approaches and perspectives in your work.
3. PARTICIPATE... in sessions that will range from state of the art lectures, to debates on hot topics in microbicides development.

Click here to learn more.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

The Future Role of Rectal and Vaginal Microbicides in Heterosexual Couples

via STI British Medical Journal, by Marie-Claude Boily, Dobromir Dimitrov, Salim S Abdool Karim, Benoît Mâsse

Objectives

To compare the potential impact of rectal (RMB), vaginal (VMB) and bi-compartment (RVMB) (applied vaginally and protective during vaginal and anal intercourse) microbicides to prevent HIV in various heterosexual populations. To understand when a RMB is as useful than a VMB for women practicing anal intercourse (AI).

Methods

Mathematical model was used to assess the population-level impact (cumulative fraction of new HIV infections prevented (CFP)) of the three different microbicides in various intervention scenarios and prevalence settings. We derived the break-even RMB efficacy required to reduce a female's cumulative risk of HIV infection by the same amount than a VMB.

Results

Under optimistic coverage (fast roll-out, 100% uptake), a 50% efficacious VMB used in 75% of sex acts in population without AI may prevent ~33% (27, 42%) new total (men and women combined) HIV infections over 25 years. The 25-year CFP reduces to ~25% (20, 32%) and 17% (13, 23%) if uptake decreases to 75% and 50%, respectively. Similar loss of impact (by 25%–50%) is observed if the same VMB is introduced in populations with 5%–10% AI and for RRRAI=4–20. A RMB is as useful as a VMB (ie, break-even) in populations with 5% AI if RRRAI=20 and in populations with 15%–20% AI if RRRAI=4, independently of adherence as long as it is the same with both products. The 10-year CFP with a RVMB is twofold larger than for a VMB or RMB when AI=10% and RRRAI=10.

Conclusions

Even low AI frequency can compromise the impact of VMB interventions. RMB and RVMB will be important prevention tools for heterosexual populations.

Read the full study here.



[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

IRMA Statement on Discontinuation of Gel Arm in VOICE Prevention Trial

25 November, 2011
IRMA Expresses Disappointment; Calls for MTN 017 to Move Forward

International Rectal Microbicide Advocates (IRMA) expresses disappointment regarding today’s announcement that the vaginal tenofovir gel arm in the Microbicide Trial Network’s (MTN) VOICE trial is being discontinued. VOICE has been exploring two ARV-based HIV prevention approaches since it began enrolling women in high incidence areas in South Africa, Uganda and Zimbabwe in 2009.

The MTN announced that the VOICE arm studying daily vaginal application of tenofovir gel was stopping after a regular review of study data conducted by the independent Data Safety Monitoring Board revealed that the gel, while safe, was not effective at preventing HIV infection in women . Less than two months ago, VOICE announced the discontinuation of its study arm testing tenofovir tablets because they also were shown to not be effective at preventing HIV in the trial. VOICE will continue to study the safety and efficacy of Truvada tablets.

“This is tough news to hear, so soon after the tenofovir tablet arm stopped, and we are certainly disappointed,” said Jim Pickett, IRMA chair. “The field has placed a great deal of hope – and resources – in the development of vaginal tenofovir gel and no one is happy about such an outcome.”

The scientific path is a long, challenging and often confounding one. While this wasn’t information anyone wanted to hear, we will learn much about why tenofovir gel did not work in this well-conducted trial. At the moment we do not know whether this was a matter of adherence, biology, or sexual behaviors – or a combination of all three.

“Too often heterosexual transmission is presumed, by default, to be through unprotected vaginal intercourse. It will be interesting to learn how much anal intercourse was being reported in the trial. Unprotected anal intercourse is 10 to 20 times more likely to result in HIV transmission compared to unprotected vaginal intercourse. If even a small portion of VOIC E participants were practicing unprotected anal intercourse, this may have confounded the efficacy of the vaginal gel being tested,” said Pickett.

It is critical that the planned MTN 017 Phase II rectal microbicide trial moves forward. MTN 017 will study a modified formulation of tenofovir gel, to be applied rectally among gay men and other men who have sex with men (MSM) in Thailand, South Africa, Peru and the United States with a proposed launch in mid-2012. While moving forward with MTN 017 is dependent on the MTN 007 study which tested rectal safety and acceptability of this gel, we expect results soon. If the results indicate this modified formulation of tenofovir gel is both safe and acceptable when used rectally, MTN 017 must happen.

“Gay men and other MSM suffer very high prevalence rates in every part of the world, and their primary exposure is from unprotected anal intercourse. It is therefore an imperative we study products for rectal use. The rectum is a more fragile environment than the vagina and has other characteristics that increase the chances for HIV infection to take hold,” said Pickett. “As anal intercourse is a human behavior not confined to gay men and other MSM – we all have rectums after all– developing safe, effective, acceptable and accessible rectal microbicides will be important to the health and well-being of millions of women and men in Africa and throughout the world.”

IRMA is pleased the FACTS 001 study, a Phase III trial in South Africa testing the same regimen of tenofovir gel used in CAPRISA 004, plans to continue. IRMA is also excited about the upcoming Phase III trial testing a vaginal ring containing the ARV dapivirine. Delivery methods such as vaginal rings may improve adherence and drug availability.

# # # #

IRMA (www.rectalmicrobicides.org), a project of AIDS Foundation of Chicago (www.aidschicago.org) is a global network of advocates, researchers, policy makers and funders committed to the research and development of safe, effective, acceptable and accessible rectal microbicides for all that need them.

[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

First combination ARV vaginal ring for HIV prevention being tested in Phase I safety trial

via EurekAlert

In the first clinical trial of a vaginal ring combining two antiretroviral (ARV) drugs, researchers from the Microbicide Trials Network (MTN) are collaborating with the International Partnership for Microbicides (IPM) to evaluate whether the ring is safe for use in women. If the ring does prove to be safe, it could be considered for further testing, and eventually be evaluated for its effectiveness as a microbicide for protecting women against HIV infection through vaginal sex.

The trial, which is funded by U.S. National Institutes of Health and goes by the name MTN-013/IPM 026, is evaluating a ring that contains the ARVs dapivirine and maraviroc. Each of these drugs works against HIV in a different way. Dapivirine belongs to a class of ARVs called non-nucleoside reverse transcriptase inhibitors (NNRTIs) that prevent HIV from making copies of itself. Maraviroc, on the other hand, is an entry inhibitor that blocks HIV from getting inside target cells.

The dapivirine-maraviroc ring is the first combination microbicide to enter clinical trials. It is also the first vaginal microbicide containing an entry inhibitor.

The ring was developed by IPM, a non-profit product development partnership headquartered in Silver Spring, Maryland, in collaboration with Queens University Belfast (Belfast, Northern Ireland). The belief is that combining the two drugs, which act at different points in the HIV "life cycle," may provide greater protection against HIV than a single drug alone.

Globally, women comprise half of the 34 million people living with HIV. In sub-Saharan Africa, women represent nearly 60 percent of adults with the virus. In most cases women – especially young women – acquire HIV through unprotected heterosexual sex with an infected partner. Because the use of condoms is often not an option, there is an urgent need for effective prevention strategies that women can control themselves. Toward this end, vaginal microbicides in the form of a gel or a ring, for example, are being developed to provide women with new tools to protect themselves against HIV.

Vaginal rings provide slow, continuous delivery of a drug or multiple drugs to cells inside the vagina over a period of weeks or months. Marketed vaginal ring products include those used for contraceptive delivery and hormone replacement. However, vaginal rings can also be used as a vehicle for delivering potent ARV drugs into the vagina to prevent HIV infection. Because they could be used for one month at a time, vaginal rings may offer a long-acting and convenient prevention option for women.

MTN-013/IPM 026, which is now screening potential participants, will enroll 48 healthy, HIV-negative women ages 18-40 at the University of Pittsburgh, Fenway Institute in Boston and the University of Alabama at Birmingham. Researchers will evaluate the ring's safety and how well women like or are willing to use the ring. In addition, different tests will be performed to help determine how much of each drug is taken up by the cells usually targeted by HIV and whether drug levels are sustained throughout the four weeks the ring is worn.

Read the rest.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Rectal! Rectal! Read all About It!

via AIDS Foundation of Chicago, by Gregory Trotter

The word elicits a certain reaction from people.

“People say the word ‘rectal’ and they -- ,” said Jim Pickett, going into a simulated full body shudder of disgust.

Pickett, chair of the International Rectal Microbicide Advocates (affectionately dubbed IRMA), would know. He’s an outspoken advocate for more research and funding in the relatively new field searching for an effective rectal microbicide, an antiretroviral gel that could be a valuable tool in saving lives by preventing HIV/AIDS.

Along with his co-panelists, Pickett was at the United States Conference on AIDS on Friday afternoon to talk about microbicides and other promising new prevention tools, such as pre-exposure prophylaxis (PrEP) and female condoms.

“If condoms work, why do even need this?” Pickett, direction of prevention policy and gay men’s health for the AIDS Foundation of Chicago, asked the group of 30 or so people gathered for the discussion.

Mumbled answers from various people essentially spoke the same truth: Often, people do not use condoms because they’re uncomfortable, and because they can inhibit pleasure and intimacy.

A vaginal microbicide is much closer to being a reality than the rectal variety, mostly because research into the latter has been slowed by years of stigma and political heel-dragging, Pickett said in a separate conversation. Whereas a vaginal microbicide is perhaps a few years away, it could be another 10 years before a rectal product is fully vetted and ready for use.

But both are essential for preventing HIV in men and women, Pickett said. Globally, women are seven times more likely to have unprotected anal sex than men, a conservative projection based on the limited data on anal sex among heterosexuals, he said.

And this biological fact speaks to the need for a rectal-specific microbicide: The rectal wall is only one cell layer of protection from viruses, as opposed to the vaginal wall, which is 20-40 cell layers thick.

But perhaps the most controversial new prevention method is PrEP.

Recent trials have proven PrEP to be effective among gay/bi men who adhere to a regimen of Truvada, the drug made by Gilead Sciences, Inc. The results have been more mixed in trials involving heterosexuals.

Read the rest.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

ARV gel almost ready to roll out

via the Daily News, by Liz Clarke

In the time it takes parents to see their children grow from birth to adulthood, the vaginal gel containing the antiretroviral tenofovir has been under close and intense scrutiny.

Now nobody is more keen to see the fast-track roll-out of the life-saving microbicide than Professor Quarraisha Abdool Karim.

Research initiated 20 years ago at the Medical Research Council and in the past ten years at Caprisa finally culminated in a definitive proof that a microbicide, namely tenofovir gel, reduces the risk of women contracting HIV.

“Twenty years might sound a long time,” she said this week, “but this sort of science requires painstaking input from every member of the research team. We have had to ensure that every avenue – from concept to proof – has been covered. Now that we can prove that tenofovir gel works, we are looking forward to implementing the next step.”

That next step, awaiting approval from the Medicines Control Council, will test the feasibility of integrating tenofovir gel provision into family planning services.

As a principal researcher in the Caprisa 004 scientific research programme, Abdool Karim demonstrated that the gel prevented both HIV and Herpes Simplex Virus (HSV) Type 2 infection.

It’s a finding that has been lauded as one of the most significant scientific breakthroughs in the fight against Aids by WHO, UNaids and several leading organisations

“But there is no time to rest on these laurels,” she says. “There is much work still to do.”

Read the rest.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

NIH researchers show how anti-HIV drug acts to block herpes virus

via Infotech

"The findings explain the results of a recent clinical trial showing that the anti-HIV drug tenofovir, when it is formulated as a vaginal gel, could reduce the risk of herpes simplex virus (HSV) infections -- as well as HIV infections -- in women.

Tenofovir taken orally had been demonstrated to inhibit reproduction of HIV, but had not been known to block the genital herpes virus.

"HIV infection is closely associated with herpes viral infection. When people with genital herpes are exposed to HIV, they are more likely to become infected than are people who do not carry the herpes virus," said Leonid Margolis, Ph.D., head of the Section on Intercellular Interactions at NICHD and one of the authors of the study. "Human tissues convert tenofovir to a form that suppresses HIV. We found that this form of tenofovir also suppresses HSV. This discovery may help to identify drugs to treat the two viruses even more effectively." Discoveries leading to new uses for previously approved drugs have the potential to save millions of dollars, Dr. Margolis said. New drugs typically undergo years of testing for safety and effectiveness before they are approved for patients. Finding new uses for an approved drug increases the value of the initial investment in testing, because most of the testing has previously been completed."

Read the rest.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

The Pharmacokinetics of Tenofovir Following Intravaginal and Intrarectal Administration of Tenofovir Gel to Rhesus Macaques

via AAC Accepts, by Jeremy Nuttall, Angela Kashuba, Ruili Wang, Nicole White, Philip Allen, Jeffrey Roberts, and Joseph Romano

Abstract

Tenofovir gel (1%) is being developed as a microbicide for the prevention of HIV infection, and has been shown to reduce transmission to women by 39%. The gel also prevents infection in macaques when applied intravaginally or intrarectally prior to challenge with SHIV, but very little pharmacokinetic information in macaques is available to help extrapolate the data to humans, and thus inform future development activities. We have determined the pharmacokinetics of tenofovir in macaques following intravaginal and intrarectal administration of 0.2, 1 and 5% gels. Plasma and vaginal and rectal fluid samples were collected up to 24 hours after dosing, and at 24 hours post dosing biopsies were taken from the vaginal wall, cervix and rectum. Following vaginal and rectal administration, tenofovir rapidly distributed to the matrices distal to the site of administration. In all matrices, exposure increased with increasing dose, and with the 1% and 5% formulations, concentrations remained detectable in most animals 24 h after dosing. At all doses, concentrations at the dosing site were typically 1-2 logs higher than in the opposite compartment, and 4-5 logs higher than in plasma. Exposure in vaginal fluid after vaginal dosing was 58-82% lower than in rectal fluid after rectal dosing, but plasma exposure was 1-2-fold greater after vaginal dosing than after rectal dosing. These data suggest that a tenofovir-based microbicide may have the potential to protect when exposure is via vaginal or anal intercourse, regardless of whether the microbicide is applied vaginally or rectally.



[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy

via PLoS ONE, by Peter A. Anton, Terry Saunders, Julie Elliott, Elena Khanukhova, Robert Dennis, Amy Adler, Galen Cortina, Karen Tanner, John Boscardin, William G. Cumberland, Ying Zhou, Ana Ventuneac, Alex Carballo-Diéguez, Lorna Rabe, Timothy McCormick, Henry Gabelnick, Christine Mauck, Ian McGowan

Objectives:

Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.

Methods:

HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.

Results:

All 36 subjects enrolled completed the 7–14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.

Conclusions:

Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538)

Read a more detailed description of the study here.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

New Microbicide May Block Virus From Infecting Cells

via The University of Utah U News Center

University of Utah researchers have discovered a new class of compounds that stick to the sugary coating of the AIDS virus and inhibit it from infecting cells – an early step toward a new treatment to prevent sexual transmission of the virus.

Development and laboratory testing of the potential new microbicide to prevent human immunodeficiency virus infection is outlined in a study set for online publication by Friday in the journal Molecular Pharmaceutics.

Despite years of research, there is only one effective microbicide to prevent sexual transmission of HIV, which causes AIDS, or acquired immune deficiency syndrome. Microbicide development has focused on gels and other treatments that would be applied vaginally by women, particularly in Africa and other developing regions.

To establish infection, HIV must first enter the cells of a host organism and then take control of the cells’ replication machinery to make copies of itself. Those HIV copies in turn infect other cells. These two steps of the HIV life cycle, known as viral entry and viral replication, each provide a potential target for anti-AIDS medicines.

“Most of the anti-HIV drugs in clinical trials target the machinery involved in viral replication,” says the study’s senior author, Patrick F. Kiser, associate professor of bioengineering and adjunct associate professor of pharmaceutics and pharmaceutical chemistry at the University of Utah.

“There is a gap in the HIV treatment pipeline for cost-effective and mass-producible viral entry inhibitors that can inactivate the virus before it has a chance to interact with target cells,” he says.

Read the rest.


[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

2012 International Microbicides Conference (M2012) in Sydney, Australia

The next International Microbicides Conference will be held in Sydney, Australia from April 15-18th, 2012!

Registration
Registration is not yet open, but to submit an expression of interest, please click here. By submitting this, you will be contacted as soon as official registration opens!

Abstract Submission
The 2012 International Microbicides Conference (M2012) invites papers of high quality in the areas of HIV prevention, with a particular focus on microbicides, oral chemoprophylaxis, and their interface with other prevention strategies. The conference is interdisciplinary, and encourages the full involvement of communities and individuals affected by HIV. Abstract submissions will be reviewed by the Scientific Program Committee for content, presentation, timeliness, and current interest of the topic to M2012 participants. Abstracts are welcomed from researchers, program implementers, policy makers, advocates, and community members, and will be considered for inclusion provided they meet the guidelines below.

Please click here to view the abstract submission guidelines.  Authors should submit abstracts no later than 5pm AEST time on Thursday 17 November 2011. Click here for more information and details about uploading your abstract.

Scholarships
Scholarships are available to attend the 2012 International Microbicides Conference (M2012) in Sydney, Australia.

Scholarships will be offered in four categories that have distinct criteria:
1. Research
2. Community
3. Government Official/Public Health Policy
4. Media (Further details to come - Media scholarships will open 23 September)

Scholarship applications are due 5:00 pm AEST on Thursday 17 November 2011.  Click here for more details about scholarships and to apply.

For any other information about M2012 please go to microbicides2012.org.

[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]