Rectal microbicide research gives hope for HIV protection

via Citizens News Service, by Somya Arora

According to the Microbicides Trials Network (MTN), HIV continues to disproportionately affect racial minorities and men who have sex with men (MSM). MTN estimates that 5 to 10 percent of the world’s population engages in anal sex and globally, MSM are 19 times more likely to be infected with HIV than the general population. Unprotected anal sex is the primary driver of the HIV epidemic among this population. The risk of becoming infected with HIV during unprotected anal sex is 10 to 20 times greater than unprotected vaginal sex, because the rectal lining being only one-cell thick, it allows the virus to easily reach immune cells to infect. 

“Rectal microbicides are critical to turn the tide of the AIDS pandemic as we know that unprotected anal intercourse is the riskiest of HIV related behaviours. Human beings, all over the world, regardless of gender and sexuality, have anal intercourse and a lot of this is unprotected because they do not have access to condoms and/or because of the mistaken notion that anal intercourse is safer than vaginal intercourse with regards to contracting HIV. Having more tools for protection, in addition to what we already have, I think would be absolutely critical,” says Jim Pickett, Director (Advocacy), Chicago AIDS Foundation and founder-chair of International Rectal Microbicide Advocates (IRMA).

In an update on the CHARM (Combination HIV Antiretroviral Rectal Microbicide) Program, Dr Ian McGowan, Professor of Medicine, University of Pittsburgh, and Co-principal Investigator MTN, informs that, “Microbicides are products that can be applied to the vaginal or rectal mucosa with the intent of preventing or significantly reducing the risk of acquiring Sexually Transmitted Infections including HIV. Combination antiretrovirals are more potent and more useful as rectal microbicides. The rationale behind the CHARM programme is that we need a rectal specific combination antiretroviral microbicide.”

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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And in the Beginning, There Were Rectal Microbicides: An Update on the CHARM Program

Please Register for this Teleconference!

 Please join IRMA, AVAC and Ian McGowan, co-principal investigator of the Microbicide Trials Network and Principal Investigator of CHARM (the Combination HIV Antiretroviral Rectal Microbicide Program) for a thoroughly CHARMing teleconference update on what is happening with this innovative program.

Funded by the U.S. National Institutes of Health in 2009, CHARM is an $11 million, five year, multicenter grant intended to advance candidate rectal microbicides from discovery into early clinical development. Rather than simply testing existing vaginal formulations of microbicides, CHARM seeks to develop rectal-specific products from the beginning.

Find out the latest on CHARM, including the development of a purely rectal formulation of tenofovir gel, and other scientific activities underway and planned.

CHARMed, for sure!

Click here to determine the time of the call in your location.
Slides will be made available on the IRMA website here , for download in advance of the teleconference, and via the ReadyTalk web interface on the day of the call. Audio for the call will be available via phone only.

Click here to Register! If you need an operator to dial you in, please let us know at rectalmicro@gmail.com.

We look forward to your participation in this global teleconference!


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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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[VIDEO] McGowan and Pickett Talk the Rectal Microbicide Walk at Microbicides 2012

Rectal microbicides were ALL OVER the Microbicides 2012 conference...

Chatting up rectal microbicide research and advocacy activities and issues at the recent Microbicides 2012 conference (held in Sydney this past April) were Dr. Ian McGowan, co-principal investigator of the Microbicide Trials Network (and IRMA Scientific Co-Chair) and IRMA Chair Jim Pickett.

Have a look/listen to their discussion with reporters.

 

*Check out pics from the Microbicides 2012 conference on IRMA's Facebook page.

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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. 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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Join IRMA for an Upcoming FREE Global Teleconference on the Latest in Rectal Microbicide Research

Rectal Microbicide Research Update - MTN 007 and MTN 017

There are exciting new developments in the rectal microbicide field. Please join IRMA and AVAC for a FREE global teleconference Thursday, March 15, 10am eastern, featuring Drs. Ian McGowan and Ross Cranston of the Microbicide Trials Network (MTN). Ian (co-principal investigator of the MTN) will share results from the MTN 007 trial - just released at CROI 2012.

Following Ian, Ross will discuss the upcoming MTN 017 trial - a Phase II safety and acceptability trial of the same gel studied in MTN 007 - which will have sites in 4 countries and will start later this year. MTN 017 is the first Phase II trial to be conducted in the rectal microbicide field, and will be the first time that trial sites from outside the U.S. are included.

Click here for more info on the call and to register.

For more info on MTN 007, click here.

For more info on MTN 017, click here.

Project ARM - Africa for Rectal Microbicides - Strategy Meeting a Success!

Originally published by IRMA colleagues at Mapping Pathways here.

“It was an amazing group, and one that moved me to near tears on a number of occasions”

IRMA chairman Jim Pickett just returned from an inspiring week in Addis Ababa, Ethiopia, where he led a strategy meeting for the  IRMA's Project ARM - Africa for Rectal Microbicides - and then attended the ICASA 2011 conference (read more about both here and here). We checked in with Jim for an update on IRMA's Project on the meeting held December 2nd and 3rd.

The meeting, which was the result of 18 months of planning and coordination, convened about 40 individuals - both invited speakers and guests, including 16 individuals who secured scholarships to attend (out of 145 applicants.) The meeting participants represented countries including Ethiopia, Rwanda, Cameroon, Kenya, Nigeria, Zambia, Malawi, Zimbabwe, South Africa, Uganda, Canada, United Kingdom, and the United States -researchers, advocates, LGBT people, heterosexual people, and those representing sex workers, prison populations and more.

“It was an amazing group, and one that moved me to near tears on a number of occasions,” says Pickett, who explained that the aim of this meeting was for people to come together and create a strategy, a road map, around rectal microbicide research and advocacy specific to the African context. “I've been to many, many meetings – too many – in my day and I think the Project ARM meeting was, by far, one of the most productive, inspiring, exciting, energizing, and emotionally moving ones I've ever had the privilege to attend. Yes, I am obviously biased - but it isn't often that events like these make me misty-eyed and put a lump in my throat – repeatedly.”

The journey to getting all these people together for this meeting was not easy, as many faced multiple challenges securing the required visas for travel to Ethiopia. Says Pickett, “There was this incredible energy in the room. We’d been planning this meeting for the past 18 months, and it has been a long journey for all of us to make this happen. A number of the people attending went to extraordinary lengths to get to Addis Ababa. They had to make so many trips to embassies and consulates for visas, so many obstacles were placed in their way to dissuade them from attending, but none of them took no for an answer. The incredible perseverance they exhibited simply to show up was extremely moving.”

The participants spent the two days together getting informed – including sharing the latest updates on rectal microbicide science, rectal microbicide advocacy, issues around LGBT crimininalization, anal sex prevalence, the gay/MSM epidemic, and more. “But we didn't just passively listen to others speak - we broke out into small groups a number of times to unpack what we learned and to come up with priorities and plans for moving forward,” says Pickett.

Four advocacy-focused items and four research-focused items were prioritized, and action steps were developed for each. These included expanded rectal microbicide scientific research activities in Africa, expanded research into anal sex behaviors among African straight and gay/MSM populations, communication/education efforts, and the birth of the Global Lube Access Mobilization (GLAM) campaign called "And Lube" to support increased access and availability of condom-compatible lubes throughout Africa. Current lubricant access across the continent is absolutely abysmal.

What especially surprised and moved Pickett was the level of enthusiasm and positivity in the room. “A lot of these people come from countries that have seriously troubling environments and where advancing HIV prevention and advocacy is met with extreme homophobia. So I thought that a lot of the discussion would be on the challenges and obstacles-- I mean, so many of the countries we were focusing on are settings where you can’t even think of doing a microbicide trial, let alone discussing sexuality openly without worrying for your safety – yet the participants didn’t get stuck on these negatives. These are men and women who are brave and strong and are committed to fighting for better health and civil rights for the people in their country. It was extraordinarily fulfilling to witness their passion and energy first hand; to see them standing up and doing this work despite the numerous challenges and obstacles in their way.”

Dr. Ian McGowan, co-principal investigator of the Microbicide Trials Network (MTN) attended the meeting, presenting the latest in rectal microbicide science. He also addressed some of the questions regarding the recent closure of the VOICE trial’s study arm testing tenofovir gel. The decision was made due to futility – while tenofovir gel was found to be safe, the trial was not able to prove the gel worked to prevent HIV. See the statement from the MTN for more information. Previously the trial had to drop its tenofovir tablet arm due to futility as well. The Truvada tablet arm in the trial is continuing. “There was a lot of speculation in the room about why it was closed,” said Pickett. Many of the people present speculated that a lack of adherence might have been a factor, said Pickett. “But of course, it’s all speculation at this point, we don’t know what happened, and we won’t till the end of next year likely.” He added that McGowan confirmed that it is still important to move forward on both vaginal and rectal microbicide research and to keep exploring ways to create a more diversified microbicide pipeline (learn more about the microbicide pipeline here and here).

For Pickett, another big highlight was McGowan’s strong validation for Project ARM’s objectives. McGowan, a highly respected veteran in microbicides research, publicly offered MTN support for future Project ARM activities and commended the participants for their collective intellect and passion. Said Pickett, “Ian participated in many of the small break-out groups, and I think he was impressed by the high quality of thought, curiosity, and energy in the room. And to have that kind of validation from someone who is one of the key rectal microbicide researchers on the planet… it was a really big moment for us. There isn’t a doubt in my mind now that Africa is squarely on the rectal microbicide map.”

Pickett also felt that an interesting backdrop to the IRMA meeting was Hillary Clinton’s speech that formalized the Obama administration’s prioritization of LGBT rights globally, helping to bolster rights’ groups on the ground in their fight against discrimination. “At the end of the day,” said Pickett, “if people aren’t free to be who they are, wherever they are, they won’t be able to make use of any prevention technology, let alone rectal microbicides. There’s no point in having a really great microbicide on the shelf if people are not safe, and therefore unable, to access it.”

Jim Pickett is the Director of Prevention Advocacy and Gay Men's Health at the AIDS Foundation of Chicago. He is chair of IRMA (International Rectal Microbicide Advocates), and a member of the Mapping Pathways team. A full report from the Project ARM meeting in Addis, laying out a rectal microbicide research and advocacy strategy for Africa will be released at the Microbicides 2012 conference in Sydney in April 2012. Until then, find updates here.

We are so proud of you Jim!!

[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.]

POZ love for IRMA - The Anal Dialogues

The July/August 2011 issue of POZ Magazine belongs to IRMA and rectal microbicides. Check it out for a nice history of our work and a snapshot of the science, including important information on lubricant safety.

via POZ.com, by Trenton Straub

Excerpt:

Perhaps IRMA’s most visible work is three game-changing reports it published in conjunction with the biennial International Microbicides Conference. The first, Rectal Microbicides: Investments & Advocacy in 2006, compiled what research was being done and where—a tricky task. “A lot of researchers were concerned that if ‘anal’ or ‘rectal’ appeared in research proposals or reports, they wouldn’t get funded, so they’d scrub their papers so those words wouldn’t show up,” LeBlanc says. “Instead, they would refer to ‘topical use of products’ or other language.” And because of the dangers surrounding the subject—male-to-male sex is illegal in many countries, including 31 in sub-Saharan Africa—IRMA first had to gain researchers’ trust, proving they were not raging advocates who would alienate and antagonize. Their professionalism paid off, and the report was a hit. “It showed we were serious,” Pickett says, “and we got hundreds of new members.” 


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.]

Pittsburgh's Dynamic Rectal Duo

IRMA Scientific Vice Chair Ian McGowan and his research/life partner, Ross Cranston (also a member of the IRMA Steering Committee) are featured in CUE Pittsburgh this month. They talk about our favorite topic - rectal microbicides - and a trial taking place right in Pittsburgh that gay men can get involved in.

The article, below, starts on Page 17. Use the arrows on both sides of the magazine to "flip" pages forward and back.

[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.]

PRESS RELEASE: Tenofovir Gel Provides High Level of Protection Against HIV in Rectal Tissue

via Microbicide Trials Network

[The abstract, RMP-02/MTN-006: A Phase I Placebo Controlled Trial of Rectally Applied 1% Vaginal Tenofovir Gel with Comparison to Oral Tenofovir Disoproxil Fumarate, is being presented at a scientific session at CROI 2011 TODAY from 10 a.m. - 12:15 p.m. ET.]



Strongest effect seen in tissue taken from participants after one week of use

BOSTON, Feb. 28, 2011 – A gel developed to protect against HIV during vaginal sex produced a strong antiviral effect when used in the rectum, according to an early-phase study presented today at the 18th Conference on Retroviruses and Opportunistic Infections (CROI). The results, based on rectal tissue biopsies sampled from HIV-negative men and women who used the product daily for one week, provide the first-ever evidence that tenofovir gel could help reduce the risk of HIV from anal sex, even though the vaginal gel formulation may not be optimal for rectal use.

Tenofovir gel was not especially well-liked by a majority of men and women in the study, yet most reported they would be likely to use the gel if it became available in the future as a method for preventing HIV. Although the study found use of the gel generally safe, side effects were problematic to a few study participants. In hopes of making tenofovir gel more acceptable for rectal use, researchers have since modified the gel and are now testing it in another study.

“We are very encouraged about these findings that indicate applying tenofovir gel topically to the rectum could be a promising approach to HIV prevention,” said Peter Anton, M.D., professor of medicine and director of the Center for Prevention Research at the University of California, Los Angeles (UCLA), who led the study with Ian McGowan, M.D., Ph.D., co-principal investigator of the Microbicide Trials Network (MTN) and professor of medicine at the University of Pittsburgh.

“These are early results, but help set the stage for current and future trials of rectal microbicides and the development of a rectal-specific formulation of tenofovir gel,” added Dr. McGowan, who is leading the second study of the new gel formulation.

Microbicides, products applied on the inside of the rectum or vagina, are being designed and tested to help prevent or reduce the sexual transmission of HIV or other sexually transmitted infections. The majority of microbicide research thus far has focused on products to prevent HIV during vaginal sex. Yet, the risk of becoming infected with HIV from unprotected anal sex may be at least 20 times greater than unprotected vaginal sex, in part because the rectal lining is only one-cell thick compared to the vagina’s multiple layers, making it easier for the virus to reach cells to infect.

The study, known as RMP-02/MTN-006, is the first clinical trial of tenofovir gel for rectal use. Last year, tenofovir gel was shown in a trial called CAPRISA 004 to reduce the risk of HIV infection in women who used it before and after vaginal sex.

Conducted at UCLA and the University of Pittsburgh, RMP-02/MTN-006 tested two products – tenofovir gel and oral tenofovir – in 18 sexually abstinent, HIV-negative men and women. Oral tenofovir, an antiretroviral (ARV) tablet commonly used to treat people with HIV in combination with other ARVs, is being explored as a means to prevent infection in people who are HIV-negative through an approach called pre-exposure prophylaxis, or PrEP.

The trial directly compared the anti-HIV activity of a single dose of oral tenofovir to a single dose of rectally-applied tenofovir gel. This was followed by six days of at-home dosing of tenofovir gel or a placebo gel, with the last and seventh dose given in the clinic. A novel approach was used to determine whether any actual protection was provided by the drug given in the different regimens – single oral, single gel and seven-day gel (or placebo) – in which small biopsies were taken from the rectal lining of the participants using a standard clinical procedure called sigmoidoscopy. The tissue samples were then sent directly to the laboratory where they were exposed to HIV to determine how well study products protected the tissue from infection.

The researchers found that HIV was significantly inhibited in tissue samples from participants who used tenofovir gel daily for one week compared to tissue from participants who used the placebo gel. While a slight anti-viral effect was noted in tissue from participants who received a single dose of tenofovir gel, the finding was not statistically significant. The single dose of oral tenofovir did not provide any protection against HIV in rectal tissue samples.

“These kinds of efforts early in the development phase of rectal microbicides can give us insight into a particular product’s potential efficacy, which enables us to better design and hasten the pace of future clinical trials,” said Dr. Anton.

According to self-reports, only 25 percent of men and women who had used the tenofovir gel said they liked it. However, when asked whether they would consider using the product in the future, 75 percent of these participants reported a high likelihood of future use. Two of the 12 participants who received tenofovir gel reported severe gastrointestinal side effects, including diarrhea and lower abdominal cramps.

“These results tell us that tenofovir gel was relatively safe to use in the rectum for most participants, but we need to address side effects to make it more acceptable to use,” said Dr. Anton, who reported the findings at CROI. “Even though three-quarters of the participants reported they didn’t like the gel, we are very encouraged that the majority would consider using such a product in the future.”

Another study, MTN-007, now underway is using a formulation of tenofovir gel with less glycerin, a common additive found in many gel-like products, in the hope that this will make it better tolerated when used in the rectum. Laboratory tests of the reformulated gel suggest it is just as effective as the original formulation but less irritating to the epithelium – the layer of cells that serves as a protective barrier inside the rectum. The study began in October 2010 and is enrolling 60 men and women at three sites – University of Pittsburgh, University of Alabama at Birmingham and Fenway Health in Boston.

In addition to Drs. Anton and McGowan, other authors of RMP-02/MTN-006 are Ross Cranston, M.D., University of Pittsburgh; Alex Carballo-Dieguez, Ph.D., Columbia University; Angela Kashuba, PharmD, University of North Carolina; Elena Khanukhova, UCLA; Julie Elliott, UCLA; Laura Janocko, Ph.D., MTN and Magee-Womens Research Institute; William Cumberland, Ph.D., UCLA; and Christine Mauck, M.D., M.P.H., CONRAD.

RMP-02/MTN-006 was a collaboration between the Microbicide Development Program at UCLA and the MTN. UCLA’s Microbicide Development Program is funded by the Division of AIDS Integrated Preclinical/Clinical Program for HIV Topical Microbicides at the National Institute of Allergy and Infectious Diseases. The study products were developed by Gilead Sciences, Inc., of Foster City, Calif., which assigned the rights for tenofovir gel to the International Partnership for Microbicides of Silver Spring, Md., and CONRAD, of Arlington, Va., in December 2006. Gilead Sciences and CONRAD provided the study products free of charge.

# # #

Additional information about the study and rectal microbicides is available here.

The Microbicide Trials Network (MTN) is an HIV/AIDS clinical trials network established in 2006 by the National Institute of Allergy and Infectious Diseases with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. Based at Magee-Womens Research Institute and the University of Pittsburgh, the MTN brings together international investigators and community and industry partners who are devoted to preventing or reducing the sexual transmission of HIV through the development and evaluation of products applied topically to mucosal surfaces or administered orally.


[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.]

Meet a Friendly Rectal Microbicide Advocate: Rita Labbett

via IRMA

“It is crucial we get the word out about all that is available to help reduce (and hopefully eradicate) HIV.  Each and every year, we as advocates, researchers, scientists and doctors have to advance and ‘up the game’ in the fight against HIV.  Rectal microbicides is something I remember when it was only in the “what if we could” stages.  Now, I am astounded on how far it has come.” –Rita Labbett, MPH

Rita Labbett, a Pittsburgh, PA native, is the Research Recruiter for Project Gel, a RO1 study being conducted under the umbrella of the Microbicide Trials Network (MTN). In her role at Project Gel, she will recruit participants for a longitudinal acceptability and adherence study of a placebo gel, including clinical and behavioral evaluations.

Labbett was introduced to IRMA by fellow advocate Dr. Ian McGowan, and as an IRMA advocate is excited to be in such great company. Besides recruiting for studies with MTN, Labbett studies the behavioral aspects of safer sex and microbicide acceptance. She is even including rectal microbicide use as a sub-topic for her Ph.D. dissertation on sexual health behaviors and myths surrounding sexual health.

When she’s not working, Labbett spends time with her busy son, Michael and loves cooking and dancing hip hop.
Read about other friendly rectal microbicides advocates

Learn more about IRMA membership

[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.]

If We Can Make it There... New York Times Goes Rectal!

New Lines of Attack in H.I.V. Prevention
via New York Times, by Donald G. McNeil, Jr.

[McNeil gets things a little confused overall in this article, sometime a bit fuzzy on the facts, but this has to be the most the New York Times has ever written on rectal microbicides, beyond the one word - "rectal." This is pretty major - the rectal agenda has made the Times!]

Rectal excerpt:

Because 95 percent of gay American men and 40 percent of heterosexual American women have had anal sex at least once during their lifetimes, according to surveys, rectal versions of the gel are being developed. Tests of new, less viscous formulations that are less likely to draw water into the rectum, making use unpleasant, will begin soon, said Dr. Ian McGowan, another leader of microbicide trials at the University of Pittsburgh’s medical school.

Gay and bisexual black and Hispanic men, who are now the highest AIDS risk groups in the United States, will be recruited soon in Boston, Pittsburgh and Puerto Rico to see if they find the gels acceptable, he said.

But first it is crucial to make sure gels don’t inflame the rectal lining, which is more fragile than the vagina’s. Since H.I.V. zeros in on activated immune cells, inflammation increases infection risk. Brief tests of irritation and acceptability will be done on people advised to remain celibate during the tests, he added. Larger trials, in which thousands of men and women regularly practicing anal sex are given gel or placebo will not begin for two to three more years.

“The rectal microbicide field is about 10 years behind the vaginal one,” Dr. McGowan said.

That is partly due to misconceptions.

“When you mention rectal microbicides, a lot of people say ‘Oh, come on,’ because they think you have to protect the whole colon, and it’s meters long,” Dr. McGowan said. In fact, researchers believe protecting only the last six to eight inches will suffice.

A 2008 British study showed that rectal tenofovir gel was very protective in monkeys that were then given anal doses of the virus that causes simian AIDS.

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.]

$17 million grant to help Pitt researcher develop anti-HIV gel

via Pittsburgh Post-Gazette, by David Templeton

Highlight:

Dr. McGowan said the size of the NIH grants reflects a change in Washington, D.C., where the Obama administration has shown greater interest in funding HIV-prevention research.

"The Bush administration had a very high level of discomfort embracing HIV prevention research in men," he said. "But I think in the Obama administration that's a non-issue. They regard domestic HIV prevention in men who have sex with men as an important research priority."

It also reflects growing awareness that not only men have anal sex.

"There's increasing evidence that men and women have anal sex, too," he said. "If we are interested in HIV prevention, we have to look at options for both men and women."

 Read more.

Pitt Receives Grants Totaling $17.5 million for Two HIV Prevention Projects: Multicenter Studies Will Develop Rectal Microbicides and Assess Their Acceptance

via Erie Gay News

A multicenter research team led by the University of Pittsburgh is developing microbicides specifically designed to prevent rectal transmission of HIV, with the further aim of assessing their safety and efficacy in lab and early clinical studies.

Funded by an $11 million, five-year grant from the National Institutes of Health, the Combination HIV Antiretroviral Rectal Microbicide (CHARM) program includes a project that will reformulate existing antiretroviral drugs into topical preparations that can be applied to the rectum, said principal investigator Ian McGowan, M.D., Ph.D., a professor of medicine and of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and an investigator at the Magee-Womens Research Institute.

“Unprotected receptive anal intercourse is the highest-risk sexual activity for HIV transmission,” Dr. McGowan noted. “Vaginal microbicides already are being extensively studied, and a similar approach might be a very effective way of preventing rectal HIV transmission. It will be critical to determine whether vaginal microbicides are safe and effective when used in the rectum, and also to develop rectal-specific products.”

Read the rest.

Magee-Womens Research Institute Receives $17.5 million for Rectal Microbicide Research

Dr. Ian McGowan* (pictured), an investigator with the Magee-Womens Research Institute (MWRI), recently received a total of $17.5 million from the National Institutes of Health (NIH) to conduct two studies involving the development of rectal microbicides.

"This is exciting for the field of HIV prevention research, and especially important in terms of moving the research and development of rectal microbicides forward," said McGowan. "We applaud the leadership and vision of our sponsors at the NIH."

Microbicides are topical products that can be applied to the rectal or vaginal mucosa with the intent of preventing, or at least significantly reducing the risk of HIV acquisition in either compartment.

Recognizing the fact that women in the developed and developing world are at risk of HIV infection through anal and vaginal intercourse, the Microbicide Trials Network (MTN), based at MWRI, is currently evaluating the rectal safety of microbicides designed for vaginal use.

Dr. McGowan’s new studies focus the research towards developing microbicide products specifically designed for rectal use.

The first grant is entitled the Combination HIV Antiretroviral Rectal Microbicides or CHARM program. This is an $11 million, five year, multicenter U19 grant that brings together research groups from the University of Pittsburgh, University of North Carolina, Johns Hopkins Medical School, CONRAD, and the University of California at Los Angeles. The U19 grant is part of the NIH funded Integrated Preclinical Clinical Program and is intended to advance candidate microbicides from discovery into early clinical development.

The second grant is a $6.5 million, four year, R01 grant entitled Microbicide Safety and Acceptability in Young Men with Dr. Alex Carballo-Dieguez as the Co-Principal Investigator. The focus of this grant is to evaluate the safety and acceptability of rectal microbicides in young, ethnic minority men who have sex with men (MSM). Funding for this study comes from the National Institute of Child Health and Human Development as well as the National Institute of Mental Health and will generate critical data from a population of young African American and Latino men who are at the highest risk of HIV infection in the United States. Clinical trial sites will be in Pittsburgh, Boston, and Puerto Rico.

"We need to develop safe, effective, acceptable and accessible rectal microbicides for the millions of women and men worldwide who need options beyond condoms," said Jim Pickett, chair of the International Rectal Microbicide Advocates (IRMA) said. "Our global network of advocates, scientists, policy makers and funders is encouraged to see this work moving forward."

Together with ongoing MTN rectal safety studies and another collaborative grant with the University of Oxford, UK, these two new grants establish MWRI as a leading center for rectal microbicide translational research and will hopefully lead to the development of safe and effective products for individuals at risk of HIV infection through unprotected receptive anal sex.
 

* Dr. McGowan is also a Professor of Medicine in the Division of Gastroenterology, Hepatology, and Nutrition at the University of Pittsburgh Medical Center, with a secondary appointment in the Department of Obstetrics, Gynecology and Reproductive Science.

IRMA on Video - IAS Webcast of Rectal Satellite Session in Cape Town

Rectal Microbicide Development - An African Perspective, a satellite session held July 19, 2009, at the IAS 2009 meeting in Cape Town, South Africa, described the role of anal intercourse (AI) in HIV transmission and discussed recent research towards the development of rectal microbicides for the prevention of AI-associated HIV infection. Data from the African continent was highlighted.

Click here for Ian McGowan (IRMA Scientific Vice Chair) and Jim Pickett (IRMA chair) on video.

Following are all of the presenters and their linked presentations.

Click here for photos from the session, on Flickr.

Chris Beyrer, US - Epidemiology of HIV among MSM in Africa: Implications for rectal microbicides

James McIntyre, South Africa and Sibongile Dladla, South Africa - Accessing MSM in Africa for health care and HIV prevention studies

Ian McGowan, US - Development of rectal microbicides

Jim Pickett, US - Go tell it on Table Mountain - rectal microbicide advocacy from here to there

Related:

IRMA's Jim Pickett guests on the Windy City Queercast to talk about the IAS Conference in Cape Town, inspiring grannies, and of course, rectal microbicides.

Click here for the podcast.

Reference: WCQ325 Jim Pickett and the International AIDS Conference 2009-09-01

Click here for pics of those inspiring grannies, and more.

Nature Medicine Covers IAS Rectal Microbicide Satellite

Nature Medicine 15, 829 (2009)
doi:10.1038/nm0809-829b

by Cassandra Willyard

Despite some disappointing results from recent trials, microbicides have been touted as a potential tool to stop HIV infection through vaginal sex. Last month, however, the International AIDS Society conference in Cape Town, South Africa dedicated an entire session to rectal microbicides for the first time. "The field is picking up momentum now," says Ian McGowan, an infectious disease expert at the University of Pittsburgh School of Medicine who organized the session. "We're beginning a new phase of clinical trials."

The current focus is on testing vaginal microbicides in the rectum. Researchers have already completed a phase 1 clinical trial to test the rectal safety of UC-781, an antiretroviral being developed for vaginal use. The results have yet to be published, but McGowan, who was a co-investigator on the study, says UC-781 seemed to be safe and acceptable. Other forthcoming trials will test the rectal safety of a vaginal microbicide that contains the anti-HIV drug tenofovir.

The rectum and the vagina are "two very different environments," McGowan says, so there is no guarantee that one product will be safe and effective both places. The vaginal lining is composed of "layer upon layer of cells," he says. The lining of the rectum, in contrast, is just one cell thick, and thus more fragile. Moreover, because the rectum feeds into the colon, a larger surface area needs to be protected. Researchers are already thinking about how to design microbicides specifically for rectal use.

Money will probably be a limiting factor, however. "It's still not clear whether there's enough will from funders to do a full-scale efficacy trial for any rectal microbicide," says Robin Shattock, an immunologist at St. George's, University of London. "That's the biggest hurdle."

[A number of our presenters' slide sets are available. Click the Community Presentations link on the IRMA website to access presentations such as "Epidemiology of HIV among MSM in Africa: Implications for rectal microbicides" and "Go tell it on Table Mountain - rectal microbicide advocacy from here to there."]

Rectal Microbicide Development - An African Perspective - IAS 2009

Please plan to join IRMA and colleagues for this exciting satellite session on Sunday, July 19 in Cape Town, South Africa

Click to enlarge

IRMA Exclusive: A Preview of New Rectal Microbicide Safety Studies

IRMA's next Global Teleconference

Thursday, March 19, 2009

Featuring presentations by Medical Research Council’s Dr. Sheena McCormack (UK - on left), UCLA’s Dr. Peter Anton (center) and Dr. Ian McGowan, University of Pittsburgh (right). Be among the first to know about upcoming rectal microbicide trials - including rectal safety studies of tenofovir and Pro2000 - from the scientists leading the efforts.

Materials will be available here in advance of the call.

Send an email here to RSVP. Call-in details will be sent to all who RSVP.

Special thanks to AVAC for hosting the call!

[NOTE - the times below were edited on March 12 - a number have changed due to daylight savings time. Please look carefully.]

Sydney – 2am Friday, March 20 (sorry Sydney!)

Kuala Lumpur - 11pm

Delhi - 8:30pm

Lagos – 4pm

Cape Town - 5pm

London (UTC) - 3pm

Washington, DC - 11am

Lima - 10am

Chicago - 10am

Seattle - 8am

Rectal Microbicide Research at CROI 2009

The prevalence of receptive anal intercourse among men and women the world over requires the research and development of safe, effective and acceptable microbicides designed specifically for the rectum as well.

Today at CROI 2009, two interesting Poster Discussions were held of special interest to IRMA members.

You can access the abstracts and actual posters for each of these.

IRMA asked Drs. Peter Anton and Ian McGowan for their thoughts regarding these important findings. You can read their remarks below.






A Phase 1 Safety and Acceptability Study of the UC781 Microbicide Gel Applied Rectally in HIV Seronegative Adults: A First in Field

Peter Anton, A Adler, E Khanuknova, J Elliott, W Cumberland, Y Zhou, A Ventuneac, A Carballo-Dieguez, C Mauck, and I McGowan

Representing David Geffen Sch of Med, Univ of California, Los Angeles, US; Translational Sci Corp, Mill Valley, CA, US; Univ of California, Los Angeles Sch of Publ Hlth, US; HIV Ctr for Clinical and Behavioral Studies, New York, NY, US; CONRAD, Arlington, VA, US; and Magee-Womens Res Inst, Pittsburgh, PA, US

Click here for the abstract.

Click here for the PDF of the poster.



Strong Ex-Vivo Suppression of HIV-1 Infection of Colorectal Explants from In-Vivo Rectal Application of UC781 Gel: A Novel Endpoint In A Phase 1 Trial

Peter Anton, J Elliott, I McGowan, A Adler, K Tanner, EJ Johnson, T Saunders, C Siboliban, E Khanukova, Y.Zhou.

Representing David Geffen School of Medicine, Los Angeles, CA,
Magee-Women’s Research Institute, University of Pittsburgh Medical School, Pittsburgh, PA

Click here for the abstract.

Click here for the PDF of the poster.


Dr. Peter Anton – "The Phase I rectal safety trial of the vaginal gel formulation of UC781 was historic in that it was the first of its kind in the field. While we determined that the gel appeared safe, well tolerated and acceptable among trial participants, it is noteworthy that we also observed signs of efficacy. Namely, this type of test could be an important new protocol the entire microbicide field might adopt as a way to help evaluate which products move forward in the pipeline.

"This Phase 1 rectal safety study for microbicides, using CONRAD’s UC781 lays the foundation for the many necessary trials to follow. This study required close, active collaboration with CONRAD, NIH and the FDA, as well as the academic research institutions (UCLA, U Pittsburgh/McGee Women’s Hospital and Columbia University).

"So, the first point is that this study has forged new territory in beginning to define relevant procedures, definitions of risk and mucosal injury.

"Second, the study itself showed great results for Phase 1: the drug and formulation appears safe by all indices measured. This bodes well for its advancing and also assisting an FDA application for vaginal use (should that prove possible) by already having a rectal safety study completed.

"Thirdly, and of great interest for future trials, were the remarkable results from the novel “explant study”, which saw a strong suppression of HIV replication (HIV was applied to tissue biopsies in the laboratory) from study subjects who had received the study drug (in vivo) 30 minutes before biopsy.

"This is the closest we can come to testing real, human, sexually-exposed tissue, already treated with a microbicide to determine if it helps to resists HIV infection. In this study, it did….a remarkable result that even we did not anticipate to this degree.

"With limited resources and the clear necessity for both vaginal and rectal microbicides, we need sophisticated tools to make the best decisions earlier about the viability of any candidate microbicide and which ones to advance to more expensive, longer studies. This is not yet an actual early marker of eventual efficacy, but it is an exciting start."

Dr. Ian McGowan – “The results of the UC781 trial, in which we observed both safety and efficacy signals after testing the vaginal gel formulation of an NNRTI, are encouraging for the field of rectal microbicides.

"Later this year, the Microbicide Trials Network will launch a new Phase I safety trial to determine the safety and acceptability of Tenofovir vaginal gel applied rectally and will co-sponsor a parallel Phase 1 trial using tenofovir gel and oral formulations with NIH’s Integrated Preclinical-Clinical Program (IPCP) for microbicides.

"There is an associated 10-20 fold increased risk of HIV transmission during unprotected anal intercourse compared to unprotected vaginal intercourse. Anal intercourse among gay men, men who have sex with men, and between heterosexual men and women is common globally. We know that much of this behavior is unprotected.

"Therefore, we need two things. first, we must have rectal safety data on all vaginal microbicides in the pipeline, because we know they will be used vaginally and rectally.

"And secondly, the prevalence of receptive anal intercourse among men and women the world over requires the research and development of safe, effective and acceptable microbicides designed specifically for the rectum as well."

Two must-read articles from IRMA members Dr. Ian McGowan and Dr. Ross Cranston

Click Rectal microbicides: a new focus for HIV prevention
by Dr. Ian McGowan
November 2008 - Sexually Transmitted Infections
Sex Transm Inf 2008;84;413-417
Click Anal cancer prevention: how we are failing men who have sex with men
by Dr. Ross Cranston
November 2008 - Sexually Transmitted Infections
Sex Transm Inf 2008;84;417-419

[Thanks for sharing. These articles, as well as other published materials of interest to IRMA members, can be found here on the IRMA website, under Other Published Materials. Dr. McGowan's, noted above, contains a paragraph on the work of IRMA!]

Achieving consensus around the definition of a microbicide

by Latifa Boyce (of the Alliance for Microbicide Development)
originally published on AIDS2008.com

The field is finally moving toward consensus around the definition of a topical microbicide. In every presentation I attended during AIDS 2008 that provided a definition of a topical microbicide, they all stated the exact same definition and it included the word "rectal." It's about time!

I attend a HIV, STI, or microbicide conference nearly every quarter and this is the first time I have heard the definition articulated in a consistent way across presentations made by researchers from different organizations with different research agendas. Researchers from the Microbicide Trials Network (MTN), Center for the AIDS Programme of Research in South Africa (CAPRISA), and the International Partnership for Microbicides (IPM), for example, were all on the same page, finally, with regard to the definition of a topical microbicide. While these researchers and organizations may all have different strategies, plans, and foci for the development of a microbicide, it was great to finally see consistency and the word "rectal" included in the basic definition of the concept.

For the record, at least for the time being, let's use this basic definition when we describe the concept of a topical microbicide: a product that can be applied to the vaginal and rectal mucosa with the intention of preventing the transmission of sexually transmitted infections, including HIV.

And, as the field grows, this definition may evolve, as it has over the past year to include the word "rectal." Some researchers are already dropping the words "topical microbicide" and replacing them with the term "topical pre-exposure prophylaxis (PrEP)," which is a bit controversial to some, but fine by me, as long as what they describe continues to include both words "vaginal" and "rectal."

Congrats to the microbicide field for reaching consensus and to two individuals in particular--Jim Pickett of International Rectal Microbicides Advocates (IRMA) and Dr. Ian McGowan--who from my perspective have been instrumental in making this happen.