Advocates Applaud Launch of MTN-017, World’s First Phase II Rectal Microbicide Study

[IRMA press release]

 

Trial Design Significantly Enhanced By Strong Community Input

October 2, 2013 – IRMA applauds the launch of the world’s first-ever Phase II rectal microbicide trial. The Microbicide Trial Network’s study, called MTN-017, will test a reduced glycerin formulation of tenofovir gel applied rectally. Volunteers consisting of gay men, other men who have sex with men, and transgender women will participate in the study at sites in the United States and in Thailand, South Africa, and Peru.

“Today feels like every holiday imaginable rolled into one,” said Jim Pickett, chair of International Rectal Microbicide Advocates (IRMA.) “The launch of the MTN-017 study is a milestone long in the making and marks a giant leap forward in the development of safe, effective, acceptable, and accessible products that could be used to prevent HIV during anal intercourse.”

IRMA is pleased to have participated in an intensive community input process with the Microbicide Trials Network that included in-person consultations with advocates and key stakeholders in Thailand, South Africa, Peru and the United States. “The dreams and desires of many men, women, and transgender individuals the world over can be heard loud and clear in the design of the MTN-017 trial. This deep collaboration between scientists and community members is key to the success of this trial and to the rectal microbicide field in general,” said Pickett.

When microbicides were first imagined, they were “vagina-centric.” While many embraced the notion of creating vaginal products women could control, the majority of the HIV/AIDS community— scientists and advocates alike— dismissed the possibility of developing rectal microbicides for use during anal intercourse as an HIV prevention method. It was not considered feasible and the pursuit was seen as hopeless, even laughable. At best, the rectal microbicide field would consist of testing vaginal microbicides for rectal safety, because these products would undoubtedly end up in the rectum despite their intended destination.

IRMA thanks the visionary scientists, advocates and funders like the U.S. National Institutes of Health who bucked prevailing “wisdom” and have remained steadfast in their commitment to developing new HIV prevention methods for use during anal intercourse.

“I feel like we are taking two giant leaps forward today. One in the fight against HIV, and the other in the fight against ignorance and small thinking,” said Pickett.

# # # #

International Rectal Microbicide Advocates (IRMA) is a global network, housed at AIDS Foundation of Chicago, comprised of more than 1,200 advocates, scientists, policy makers and funders focused on rectal microbicide research and advocacy and related issues such as access to safe, condom-compatible lubricants.

Learn more about the MTN-017 study here.

Watch this video “The Rectal Revolution is Here: An introduction to rectal microbicide clinical trials” in English, Spanish, or Thai.

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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.

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Adherence to rectal microbicide use among mainly ethnic minority young MSM: lessons from a 3-month placebo gel trial at three US sites [IAS 2013]

Oral paper presented by Alex Carballo-Diéguez at IAS 2013.

 

Click for slides.

Abstract:

Background: Adherence to product use is the cornerstone of microbicide studies. This is the first study to assess how frequently mainly ethnic minority MSM, ages 18-30, with a history of unprotected receptive anal intercourse (RAI) in the prior year, would self-administer gel using a rectal-specific applicator prior to RAI in their everyday lives.

Methods: Recruitment took place in Boston, MA; Pittsburgh, PA, and San Juan, PR. Participants received 40 applicators prefilled with 4mL of hydroxyethylcellulose placebo gel that they could use over 12 weeks. They were asked to self-administer a dose within 90 minutes prior to RAI and report RAI and gel use at least weekly through an interactive voice response system (IVRS). At week 12, they responded to a Computer Assisted Self Interview (CASI) and underwent an in-depth interview. Participants were repeatedly counseled that the study focused on product adherence and that the gel would not protect against HIV.

Results: 124 MSM were enrolled (Mean age 23.1; 41% White, 40% Latino, 8% African American, 11% mixed/other). 95 participants completed the trial (18 were lost to follow up and 11 withdrew). Based on the IVRS, (n=94, 1 missing data), 88 participants had RAI (Median 10 occasions) using gel on 81.1% of occasions (SD 23.3, range 0-100). Based on CASI, (n=86, 9 refused to answer RAI question) 83 participants had RAI (Median 12 occasions) using gel on 81.7% of occasions (SD 26.7; 0-100). Based on CASI, 69% of men typically applied gel immediately before RAI; 40 inconsistent users gave as reasons not having gel with them (85%), forgetting to use it (48%), not wanting to use it (13%), partner refusal (10%) and gel messiness (10%).

Conclusions: Ethnically diverse young MSM with a history of unprotected RAI showed high adherence to gel use. Adherence to product use could potentially be enhanced by improving portability, facilitating the development of routines to counteract forgetfulness, and improving motivation and partner negotiation skills. Participant retention was challenging and needs further study. Two different self-report methods provided convergent results. Limitation: A product of known efficacy could have different uptake than the placebo used in this study.


Click for slides.

 
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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 1,200 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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Meet Coco Alinsug, A Friendly Rectal Microbicide Advocate

Check out this interesting mini-bio of  Coco Alinsug, the latest in IRMA's "Meet a Friendly Rectal Microbicide Advocate" series on the IRMA website here.  Coco is one of five new bios posted this week.

  
Coco Alinsung
Boston, Massachusettes, USA

A native of the Philippines and a resident of Lynn, Massachusetts with his partner, Coco Alinsug has made a lifelong commitment to devote his time and energy to social justice, HIV/AIDS prevention, and issues facing LGBT youth.

Coco started his career as an HIV Counselor and Tester at the Gay and Bi Men's Health Program in Beverly, MA and later was appointed as the Executive Director of the North Shore Alliance on GLBT Youth which is funded by the Massachusetts Department of Public Health to provide HIV/STI education to youth 14-24 years old - a position he has held for eight years.

Currently Coco works as the Clinical Trials Field Recruitment Manager at The Fenway Institute where he has been for nearly seven years. It was in this role that Coco first came into contact with rectal microbicide advocacy as he was tasked with recruitment for all clinical trials, including the rectal microbicide study called Project Gel.

In his role at Fenway, Coco oversees outreach and recruitment for research studies looking at everything from possible HIV vaccines to microbicides to the use of pre-exposure prophylaxis (PrEP) to prevent HIV transmission. Coco and his team travel around New England, educating people about HIV and STD transmission and safer sex practices while also recruiting potential study participants.

Coco is also Chair for Community Education and Recruitment group for both HIV Vaccine Trials Network (HVTN) and HIV Prevention Trials Network (HPTN) and sits as a member of the protocol team for two studies, HVTN505 and HPTN069. Coco also is a consultant for various HIV and STD Outreach Programs both in the North Shore and Boston, and sometimes organizes and hosts shows in several clubs.

Coco would also like to encourage IRMA to keep up the good work and always stay fabulous.

Thank you for all your work Coco, and you stay fabulous too!


------------------- *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. -------------------

Now Playing - The Rectal Revolution is Here

--- Now Playing ---  

"The Rectal Revolution is Here: An introduction to rectal microbicide clinical trials" on YouTube.

The vid, developed by IRMA, Microbicide Trials Network, and Population Council, is available in English,  Spanish and Thai languages.

Watch to learn about the need for rectal microbicides, how clinical trials work, and the importance of volunteers in the effort to make safe, effective, acceptable and accessible new HIV prevention tools.

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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 1,200 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 microbicide research takes giant leap forward with groundbreaking educational video

HIV prevention organizations debut The Rectal Revolution Is Here: An Introduction to Rectal Microbicide Clinical Trials in advance of first-ever Phase II rectal microbicide trial

 

[Press Release]

International Rectal Microbicide Advocates (IRMA), the Population Council, and the Microbicide Trials Network (MTN) today released a collaborative video project called The Rectal Revolution Is Here: An Introduction to Rectal Microbicide Clinical Trials. The jointly produced video, the first of its kind, is designed to educate communities affected by HIV about rectal microbicide development and the importance of participating in clinical trials to help speed the search for new HIV prevention options.

"The Rectal Revolution will be an excellent tool for education and recruitment for MTN-017, the first-ever Phase II safety trial of a rectal microbicide planned to launch soon. The video will be particularly useful because it's not protocol-specific and can be used in future rectal microbicide trials as well," said Clare Collins, MTN associate director of communications and external relations and video co-producer.

"There is an engaging mixture of animation and live action with beautiful footage from Thailand, South Africa, Peru, and the United States," Collins continued, "and we showcase interviews with scientists, advocates, and an exceptional rectal microbicide trial participant, Rig Rush, who is both eloquent and entertaining as he shares his personal experience as a study volunteer."

Produced by Paw Print Productions of Cape Town, South Africa, the video is available for viewing now on YouTube in English, Spanish, and Thai.

"This educational video is a groundbreaking tool to recruit volunteers and educate public health leaders for what may be one of the most promising new methods to fight HIV," said co-producer Barbara Friedland, associate in the HIV and AIDS program at the Population Council. "It was developed through an intense consultative process to ensure accuracy and relevance to the communities where this video will be shown," she said.

"We wanted the video to be educational and engaging, and to encourage audiences to get involved in efforts to prevent HIV," Friedland continued."So we worked with an advisory committee comprising staff at rectal microbicide trial sites, scientists, advocates, and other community experts to develop the script. We screened 'rough cuts' of the video with 80 professionals in the field and pre-tested it in 13 focus group discussions with over 100 gay men and transgender women in Thailand, South Africa, Peru, and the United States," she said.

"The insights and wisdom these individuals shared with us were absolutely critical to shaping the final version of the video," said Friedland.

Major funding and support for the project was generously provided by the MAC AIDS Fund, the MTN, and the Population Council, through a grant from the Swedish Ministry of Foreign Affairs.

The video debut precedes the soon-to-be launched landmark study being conducted by MTN to test a reduced-glycerin formulation of tenofovir gel among gay men, other men who have sex with men, and transgender women for safety and acceptability. MTN-017 is not only the first-ever Phase II study of a rectal microbicide, it is also the first time rectal microbicide research is expanding outside the United States and going global, with sites in Thailand, South Africa, Peru, and Puerto Rico.

"IRMA and the Population Council enthusiastically support the start of MTN-017," said Jim Pickett, IRMA chair. "The 186 individuals who will volunteer for the trial will more than double the total number of people who have participated in rectal microbicide clinical trials to date. The study will mark a giant leap forward for the field of rectal microbicides and will set the stage for future large-scale efficacy trials," he said.

Pickett continued, "the day we have a safe, effective, and acceptable rectal microbicide as a much-needed HIV prevention option for people who engage in anal intercourse is within our sights—these are truly revolutionary times and we couldn't be more energized."

Learn more about the MTN-017 trial here.

###


IRMA, the Population Council, and MTN encourage HIV prevention advocates and community educators to screen The Rectal Revolution Is Here in their own workshops and sensitization sessions and to share it widely. To receive a copy of the video in English, Spanish, or Thai, please contact IRMA at rectalmicro@gmail.com.

Editorial notes:

Currently in development, microbicides are products (gels, lubricants, films) that could be applied in the rectum or the vagina to reduce the risk of HIV infection.

Unprotected anal intercourse is 10 to 20 times more likely to result in HIV infection compared to unprotected vaginal intercourse. Unprotected anal intercourse—a common human behavior—is a significant driver in the global HIV epidemic among gay men and transgender women as well as among heterosexuals.

IRMA, based at AIDS Foundation of Chicago, is a global network of more than 1,100 advocates, scientists, policy makers, and funders from six continents working together to advance a robust rectal microbicide research and development agenda. The "bottom line in HIV prevention," IRMA addresses the institutional, socio-cultural, and political stigma around the public health need for rectal microbicide research, and advocates to increase funding and commitment within this field of inquiry.

The Population Council confronts critical health and development issues—from stopping the spread of HIV to improving reproductive health and ensuring that young people lead full and productive lives. Through biomedical, social science, and public health research in 50 countries, we work with our partners to deliver solutions that lead to more effective policies, programs, and technologies that improve lives around the world. Established in 1952 and headquartered in New York, the Council is a nongovernmental, nonprofit organization governed by an international board of trustees.

 

The Microbicide Trials Network is a U.S. National Institutes of Health-funded worldwide collaborative clinical trials network focused on preventing the sexual transmission of HIV. Recognizing the importance of microbicides research to HIV/AIDS prevention, the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), established the Microbicide Trials Network (MTN) in 2006, with co-funding from the NIH’s National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The MTN brings together international investigators and community and industry partners devoted to reducing the sexual transmission of HIV through the development and evaluation of products used orally or applied topically.

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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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Clinical Trials Have Gone Global: Is This a Good Thing?

via plosmedicine.org, by Trudie Lang and Sisira Siribaddana

Why Do We Need Trials and What Makes a Trial a Trial?

Clinical trials are needed globally to reduce disease burdens by helping developing safe and effective new therapies and vaccines. These solutions may be for non-communicable diseases like cancer and diabetes, or, as is especially needed in the poorest regions of the world, infectious disease. Developing countries are under-represented in research due to lack of commercial viability and trained researchers, yet it is in these poorest regions where research-led solutions could bring the greatest impact to high rates of early mortality.

As a research tool clinical trials are fundamental in the effort to develop new products by gaining the data required by regulators, whether for product license extensions for existing therapies for common ailments or to bring cutting edge new therapies and vaccines into approved use. However, there is also a need for clinical trials to bring evidence to determine how to improve the management of health issues; these studies often do not involve a medicinal product but instead compare different options, such as different types of management of an illness in hospital with community-based care. Or, for example, a clinical trial might be used to assess different mechanisms to improve patient adherence to therapy. These pragmatic disease management trials can bring about significant improvements in public health and often require large yet simple trial designs.

The World Health Organization and journal editors define clinical trials as “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes” [1]. Patients may be randomised to an intervention involving either an investigational new product or the standard-of-care treatment, or the patient might be randomised to be cared for by nurses who have been trained in one of two or more comparative ways.

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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An Analysis of PrEP Data and Decisions Taken in 2011

via Treatment Issues, by Deirdre Grant

More than a decade ago, “AIDS Drugs for Africa” was one of the rallying cries for a global activist movement.The meaning was simple: treat HIV-positive people with potent, life-saving medications regardless of where they live, how much money they have or who they love. These days, the phrase has more meanings than we could have ever imagined. The past two years have brought a range of data on the use of antiretrovirals for HIV prevention in HIV-negative people, as well as a preventive strategy in HIV-positive people. These developments are exciting, but the situation is far from simple. There are questions about feasibility and about levels of effectiveness observed in different trials. Today, many people want to know: Can antiretrovirals (ARVs) be used for HIV prevention in HIV-negative people? If so, which types of products, programs and for which populations is this prevention most effective?

The answers to these questions depend on several factors, including science, policy, funding, community demand, andthe future of treatment access for people with HIV. Not surprisingly, the possibility of using an ARV based prevention method in HIV-negative people generates strong opinions, both in favor of such a prevention tool and those opposed. In light of the potential, many questions have arisen including: Is it feasible? Will people actually use a pill or a gel once a day? Is it ethical, given the enduring need for ARVs for HIV-positive people worldwide? And, do we know enough from the trials to-date to describe levels of safety and effectiveness anticipated in a real world health care setting?

None of these questions have been completely answered. But over the past year, there has been a steady stream of developments that have both complicated and clarified the discussions. Mixed data on topical PrEP, such as the vaginal microbicide 1% tenofovir gel, and oral PrEP in women have left scientists and advocates perplexed. Many fear that the obstacles inherent in providing ARVs to HIVnegative people—repeated HIV testing, the need to ensure access for HIV-positive people, additional staffing requirements, and more—will overshadow the potential of these new tools. For advocates who want to see a full exploration of what ARV-based prevention can do in their communities, it’s as important as it has ever been to stay informed of developments as they emerge and maintain a firm pursuit of the ultimate goal: to curb the epidemic by preserving health in HIV-positive people and preventing as many new infections as possible.

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.]

NYT: Setback on PrEP Results May Have Been Misunderstood

via The New York Times, by Donald G. McNeil Jr.

The failure of a daily pill to protect healthy African women against AIDS may not have been the pill’s fault but the women’s reluctance to take it, scientists at an important AIDS conference in Seattle were told this week.

Last April, a promising trial of “pre-exposure prophylaxis” — giving small protective doses of antiretroviral drugs to uninfected people — was stopped early because women were getting infected anyway. It was a discouraging setback.

But scientists at this week’s Conference on Retroviruses and Opportunistic Infections who analyzed blood samples taken from the women reported that only a quarter of those who got infected had any of the drug, Truvada, in their blood. That suggested they had not taken their pills.
Papers presented at the four-day conference offered findings both optimistic and scary. There were hints at a possible way to flush the virus out of its hiding places in cells, and at ways to let some patients safely take “vacations” from triple therapy.

It is not known why so few African women took their Truvada, but there is still an enormous stigma about AIDS in Africa, and a bottle of AIDS drugs in the home implies that someone there is sick, said Mitchell Warren, executive director of AVAC, a prevention advocacy group. Mr. Warren pointed out that Truvada had protected women in a different study that enrolled established couples in which only one partner was infected.

In a different study, researchers from the University of North Carolina at Chapel Hill showed that they had used a cancer drug, vorinostat, to purge the virus hiding in the CD4 cells of six men who were already doing well on triple-therapy cocktails.

Although the cocktails can make the virus vanish from the blood, it hides in different types of cells, ready to roar back if the patient stops taking the cocktails.

Another small trial, at the Wistar Institute in Philadelphia, gave patients synthetic interferon — a virus-blocker normally made by the human body — while they took “holidays” of up to six months from triple therapy. Nine of the 20 patients did not see their viruses rebound to dangerous levels. That result will not change clinical practice right away, said Dr. Luis J. Montaner, who led the study, but suggested an alternative to lifelong triple therapy, which can be debilitating.

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.]

Researchers at CROI 2012 Share First Trial Results on Injectable HIV Drug Used as Prevention

via AidsMap.com, by Gus Cairns

The first trial in humans of an injectable, once-a-month formulation of an HIV drug has found that drug levels were maintained at a level that should in theory be high enough to protect recipients against infection, and that the drug has so far produced very few side effects. The research was presented at the 19th Conference on Opportunistic Infections (CROI), in Seattle.

The small trial at the St Stephen’s AIDS Trust (SSAT) at London’s Chelsea and Westminster Hospital gave 27 women and six men a single injection of the long-acting formulation of the drug rilpivirine, which was licensed as an oral HIV treatment last year as Edurant and is also in the tenofovir/FTC/rilpivirine pill Complera. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) drug and is especially suitable to be turned into a long-lasting injectable form because the daily dose of it required to suppress HIV is very small.

No other HIV drugs are currently in a usable long-lasting injectable form, which will limit the use of long-acting rilpivirine (RPV-LA) in combination therapy, but it could conceivably make an ideal candidate as a prevention drug, as people would not need to remember to take it every day. Other preventative drugs already formulated as monthly injections include the injectable contraceptive Depo Provera and some anti-psychotic drugs.

SSAT recruited 27 HIV-negative women aged 18 to 50, more than 50% of them black African or Caribbean, for the trial and gave them one of three doses of RPV-LA as an intramuscular injection: 300, 600 or 1200mg (the oral dose of RPV is 25 mg/day). Drug levels were then measured over the course of the next twelve weeks in blood, vaginal fluid and in vaginal tissue samples. A substudy gave six men the 600mg dose and measured RPV-LA levels in blood, rectal fluid and rectal tissue samples.

Thirty days after injection, blood and vaginal fluid levels of rilpivirine were about 60 nanograms per millilitre (ng/ml) in both blood and vaginal fluid in women given the 600mg dose, and about 80 and 120ng/ml respectively in women given the 1200mg dose. Blood levels in men given the 600mg dose were about 70ng/ml at 30 days. For comparison, the trough levels of rilpivirine in people taking daily oral doses is about 140ng/ml; but the EC50 (the amount needed to reduce viral replication by 50%) in newly-infected T-cells is 27ng/ml. It is thought these levels should be adequate to prevent HIV infection.

Over the time period, levels of drug seen were about 80% higher in vaginal fluid than in blood in women taking the 300mg dose and about 20% higher in the other two doses: conversely, drug levels in vaginal tissue were about 25% lower than in blood, and 50% lower up to day 14 in the 300mg dose group.

Drug levels in rectal fluid were low but it is thought this was due to sample contamination: concentrations in rectal tissue were about the same as concentrations in blood.

The trial participants complained of very few side-effects apart from tenderness and some swelling at the injection site. There were no allergic reactions, psychological symptoms or effects on heart rate. Safety is of course a major consideration in a drug that remains in the body for up to twelve weeks.

Researcher Akil Jackson said, "There is an obvious need in HIV prevention and treatment for formulations that reduce the need for the user to depend on daily administration,” but added that these were very preliminary results and did not establish what dose would actually be protective. Further safety and drug-level studies in HIV-negative volunteers are to be conducted at the University of Pittsburgh, home of the Microbicide Trials Network, before the drug is given to volunteers with HIV.

 
[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.]

CROI Reports Rectal Tenofovir Trial Results

via AidsMap.com, by Gus Cairns

A gel containing 1% tenofovir formulated specifically for rectal use was much better tolerated than gels used in previous rectal microbicide trials when used in a safety study in 65 HIV-negative men and women, the 19th Conference on Retroviruses and Opportunistic Infections (CROI) heard yesterday.

The gel was also compared with other gels for any irritant or inflammatory effect on tissues. These tests included an in-depth ‘microarray’ analysis of a large panel of different human genes and uncovered a previously unsuspected effect: the tenofovir in the gel appeared to modulate the activity of a large number of genes in rectal tissue cells, primarily in the direction of reducing their activity.

Whether these genetic changes will have a synergistic or antagonistic effect on the efficacy of a tenofovir-based rectal microbicide is completely unknown as yet but illustrates that nucleoside antiretroviral drugs in topical formulations may have unexpected side-effects, as they do when used as treatment.

Background

Last year a study presented at CROI (Anton) found that a 1% tenofovir microbicide gel formulated for vaginal use (similar to the one used in the CAPRISA 004 trial) inhibited HIV infection of rectal cells taken from people using the microbicide by 80%. However the microbicide was unpopular in users, with only 25% reporting liking it, the majority of people reporting side-effects like diarrhoea, cramps and discomfort, and two out of eighteen subjects reporting severe side-effects that necessitated stopping use of the gel.

These side-effects, it is thought, are due to the gel having a high osmolality. This means it contains more salts than body fluid and this causes it to draw water out of cells, resulting in diarrhoea and abdominal discomfort. The Microbicide Trials Network therefore devised a low-glycerine formulation gel with an osmolality of 800 compared with 3000 for the CAPRISA 004 gel; the osmolality of body fluids is 300. Hyper-osmolar gels also strip cells away from the rectal lining and may actually increase vulnerability to HIV and STIs when used during unprotected sex.

Acceptability

The new formulation of the gel was far more popular and easier to tolerate than the vaginal one. Acceptability was nearly 87% as opposed to 25% last year for the tenofovir-containing formulation, 93% for the HEC placebo and even 67% for the gel containing N-9. Amongst specific side-effects, 16% versus 50% last year said they had regular diarrhoea while none, as opposed to 42% last year, experienced the need to rush to the toilet as soon as they applied the gel.

Inflammation markers and genes

Samples were taken from rectal tissues 9 centimetres and 16 centimetres inside from the anal opening and various tests made on inflammatory indicators and gene expression. Not surprisingly, the N-9 gel had the most effect on inflammatory markers, raising some and suppressing others.

Samples were tested using a ‘microarray’, a testing plate that detects the effect of the gels on hundreds of individual human genes and whether they are ‘switched on’ or supressed.

The effect of the HEC gel was completely neutral on genes, with fewer activated or suppressed than in the 16 people not using gel (16 genes versus 23). The N-9 gel affected 116 genes, mostly in the direction of increasing their activity. But the tenofovir gel affected 533 different genes, mostly in the direction of decreasing their activity.

Implications


The clinical significance of this is unknown, and processing the consequence of such a large number of changes in gene activity will take a long time. But Ian McGowan told aidsmap that the results, though unexpected, were not inexplicable.

“Tenofovir is a DNA chain terminator,” he said. “This is how it stops HIV.” He pointed out that the NRTI (nucleoside) drugs were well known for side-effects which had genetic causes ranging from fat loss (caused by damage to mitochondrial genes) through bone synthesis to nerve damage.

Essentially what this study shows is that, once the ‘noise’ from direct inflammation is taken away, it can be seen that NRTI drugs have direct effects on DNA activity in cells when applied topically, just as they do when taken orally. Whether these effects have any clinical consequences remains to be seen.

The next step will be a study called MTN017 in which tenofovir gel will be administered for eight weeks.




[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.]

FEM PrEP Study Releases Trial Results

via MedPage Today, by Ed Susman

Pre-exposure prophylaxis with antiretroviral drugs failed to prevent women in Africa from becoming infected with human immunodeficiency virus (HIV) – apparently because more than half the women failed to take their medication.

The incidence of HIV infection among previously uninfected women treated with a co-formulation of emtricitabine and tenofovir (Truvada) was 4.7 per 1,000 person-years compared with a rate of 5 per 1,000 patient-years among women in the placebo group (P=0.81), said Lut Van Damme, MD, PhD, senior scientist at FHI 360, in Durham, N.C.

In a press briefing here at the Conference on Retroviruses and Opportunistic infections, Van Damme said it was likely that lack of adherence resulted in the failure to show a difference between those women on the active antiretrovirals and those who received placebo.

"The women in the study seriously overestimated adherence," she said. The participants told researchers that they took their assigned medicine 95% of the time. Pill counts indicated that 85% of the pills were not returned at regular points in the trial. But tests for emtricitabine/tenofovir in the blood of patients showed that only about 40% of the women had levels of the drug that would indicate the pills had been ingested within 48 hours of the tests.

The study was stopped early when an interim analysis showed that it was unlikely to prove positive.

The so-called FEM-PrEP was a randomized, double-blinded, placebo-controlled trial of once-daily oral emtricitabine/tenofovir. The primary effectiveness endpoint was incident HIV infection during 52 weeks of follow-up.

Participants attended screening, enrollment, and follow-up visits monthly. HIV seroconverters were taken off the product and followed for an additional 52 weeks

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.]

Identifying at-risk populations to enroll and maintain in HIV prevention trials

via PubMed, by Price MA, Rida W, Mwangome M, Mutua G, Middelkoop K, Roux S, Okuku HS, Bekker LG, Anzala O, Ngugi E, Stevens G, Chetty P, Amornkul

"Finding, enrolling, and retaining risk populations for HIV prevention trials is challenging in Africa. African MSM are not frequently engaged for research, have high HIV incidence, need urgent risk reduction counseling, and may represent a suitable population for future HIV prevention trials."

Objective

To identify and describe populations at risk for HIV in 3 clinical research centers in Kenya and South Africa.

Design

Prospective cohort study.

Methods

Volunteers reporting recent sexual activity, multiple partners, transactional sex, sex with an HIV-positive partner, or, if male, sex with men (MSM; in Kenya only) were enrolled. Sexually active minors were enrolled in South Africa only. Risk behavior, HIV testing, and clinical data were obtained at follow-up visits.

Results

From 2005 to 2008, 3023 volunteers were screened, 2113 enrolled, and 1834 contributed data on HIV incidence. MSM had the highest HIV incidence rate of 6.8 cases per 100 person-years [95% confidence interval (CI): 4.9 to 9.2] followed by women in Kilifi and Cape Town (2.7 cases per 100 person-years, 95% CI: 1.7 to 4.2). No seroconversions were observed in Nairobi women or men in Nairobi or Cape Town who were not MSM. In 327 MSM, predictors of HIV acquisition included report of genital ulcer (Hazard Ratio: 4.5, 95% CI: 1.7 to 11.6), not completing secondary school education (HR: 3.4, 95% CI: 1.6 to 7.2) and reporting receptive anal intercourse (HR: 8.2, 95% CI: 2.7 to 25.0). Paying for sex was inversely associated with HIV infection (HR: 0.2, 95% CI: 0.04 to 0.8). 279 (13.0%) volunteers did not return after the first visit; subsequent attrition rates ranged from 10.4 to 21.8 volunteers per 100 person-years across clinical research centers.

Conclusions

Finding, enrolling, and retaining risk populations for HIV prevention trials is challenging in Africa. African MSM are not frequently engaged for research, have high HIV incidence, need urgent risk reduction counseling, and may represent a suitable population for future HIV prevention trials.


[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.]

ANRS launches first PrEP trial for gay men in Europe

via iPrEx NEws

The ANRS (French National Agency for Research on AIDS and Viral Hepatitis) is about to launch in Europe the first pre-HIV exposure prevention trial in men who have sex with men.

This phase III trial—ANRS IPERGAY—will start at the end of January 2012, in Paris (Hôpital Saint-Louis, Professor Jean-Michel Molina and Hôpital Tenon, Professor Gilles Pialoux) and Lyon (Hôpital de la Croix-Rousse, Dr Laurent Cotte), and later in Montreal in Quebec (CHUM Hôpital Hôtel Dieu, Dr Cécile Tremblay). The trial will include 300 volunteers in the pilot phase and ultimately 1900 in total.

ANRS IPERGAY will involve men who have sex with men and seronegative trans men who have anal sex with men without routine use of condoms, with at least two different sexual partners in the six months prior to trial participation. Participation will last for between 12 (minimum) and 48 (maximum) months.

The trial will compare two groups of participants, one given Truvada®, the other a placebo, taken in both cases during the period of sexual activity, starting before sexual relations and ending afterwards.

All participants, irrespective of group, will be offered various means of prevention: free condoms, regular HIV screening, regular screening for and treatment of sexually transmitted diseases, vaccination against hepatitis A and B. Participants can ask for personalized prevention advice, if they wish.

An important part of the trial will involve a social sciences study of the profiles of participants and analysis of their sexual behavior, in particular regarding condom use, and will determine whether or not they take the medication as intended.

Participants will be invited to the hospital every two months or so for an interview and for clinical examinations, including screening tests.
The ANRS will sponsor and fund the trial, and Gilead will supply the medication.

The HIV community-based association Aides helped draw up the protocol, is a scientific and operations partner in the trial, and is a member of the scientific board. It will coordinate recruitment in the field and provide volunteers with prevention support.

ANRS press contact:
Marie-Christine Simon – Tel : +33 (0) 1 53 94 60 30 marie-christine.simon@anrs.fr



[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.]

From Tuskegee to Transparency: An Evolution in the Ethics and Accountability of Clinical Trials Involving Human Subjects

via RH Reality Check, by Anna Forbes and Kate Ryan

People who participate in clinical trials take the enormous step of volunteering to test a product that may be useful and, sometimes, life-saving if it turns out to be effective. They play an irreplaceable role in research to prevent, treat, and sometimes cure illness – as well as to find other ways to improve people’s health and lives.

Trial participants make a profoundly personal contribution and accept potential medical, social, and personal risks on behalf of others. An ethical trial is one that eliminates or minimizes participants’ risks as much as possible, invests in making sure that participants understand clearly what they are volunteering for, and protects their rights at every step.

For example, without clinical trials, we would not have seen recent advances in antiretroviral drugs to treat HIV, long-acting contraceptive choices that allow women greater control over their use, or microbicides that may be able to protect women from HIV.

The United States government has rules to protect people who participate in federally-funded biomedical and behavioral research. The rules vary depending on which agency is supporting the research, but they all share a starting point known as the Common Rule, a set of regulations for all federally-funded research involving human participants, whether it is conducted inside or outside the U.S.

But those rules have not always been in place, and there are some shameful chapters in the history of medical research supported by the United States that include violations of the most basic standards of ethical behavior. This history has left some people deeply suspicious of clinical trials and the motives of those who conduct them. Many explain their suspicion with one word: “Tuskegee.”

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.]

Meet Yaa Simpson: Another New Friendly Rectal Microbicide Advocate!

“Stigma is only dispelled by shining a brighter light on it! We have to speak life and light with our words and actions. There is enough doom and gloom to impact everyone - and that is where stigma resides. But letting people know they have options, biomedical techniques for prevention, medications, possible vaccines, gathering more evidence, integrating creative research designs, etc. are all steps in the right direction. We must expect the impossible and believe in miracles!”

Yaa Simpson is an IRMA advocate from Chicago, Illinois. She is an epidemiologist for the Chicago Department of Health and a Community Epidemiologist for TACTS (The Association of Clinical Trial Services). She loves to contribute to ideas and discussion about better research in the community, specifically HIV/STI prevention trials. She is also working towards her doctoral degree and hopes to one day conduct HIV prevention trails in Chicago.

Yaa first learned of IRMA when she was invited to a presentation on microbicides several years ago. Here she was introduced to Jim Pickett and his work with IRMA. She remembers Jim saying, “We all have opinions, like we all have booties!” She now is an active member on the listserv and enjoys IRMA’s blog and educational teleconferences.

She believes rectal microbicides are an important tool to add to the prevention technology toolbox, and acknowledges that we must develop technologies to prevent HIV spreading through any avenue, including rectally.

Her advice for IRMA is to continue to be involved with people who want to see change! “Talk to those who don’t want to hear about it and strategize with those who are looking for answers. Be diligent and be patient. And if you ever feel discouraged or overwhelmed by the stigma associated with standing up for rectal microbicides, remember what Mark Twain once said: 'Keep away from people who try to belittle your ambitions. Small people always do that, but the really great make you feel that you, too, can become great.'”

Read more bios from Friendly Rectal Microbicide Advocates.



[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.]

Bacterial Bioshield Could Keep HIV at Bay

Via New Scientist.

A LIVING microbicide reduces HIV-like infection in monkeys, and might one day provide women with long-lasting defence against the virus.

Dean Hamer of the National Institutes of Health in Bethesda, Maryland, and colleagues engineered naturally occurring vaginal bacteria to produce the anti-HIV protein cyanovirin-N.

They applied a gel containing the bacteria to the vaginas of rhesus macaques before infecting them by the same route with a hybrid of SIV and HIV. The engineered bacteria cut the infection rate by 63 per cent (Mucosal Immunology, DOI: 10.1038/mi.2011.30).

Human females have 10 times as much of the bacteria as female macaques, so the engineered bacteria could reduce infection rates even more dramatically, says Hamer. Clinical tests could begin in a few years after safety testing.

[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, Long-Term PrEP Study Announced

Via Now Chelsea, by Sam Spokony.

Few methods of HIV prevention have been as promising, or as controversial, as pre-exposure prophylaxis (PrEP). After a history of underground practice and off-label prescriptions, the approach has recently begun to receive serious attention from researchers, policy makers and health care advocates.

An outgrowth of post-exposure prophylaxis (or PEP, a short-term antiretroviral treatment that has been used since the early 90s to decrease the likelihood of HIV infection after exposure to the virus, either occupationally or through sex), PrEP is a similar antiretroviral that can be taken by HIV-negative individuals in order to help prevent them from seroconverting (being infected).

The results of a Phase III clinical study known as iPrEx were published in the New England Journal of Medicine on November 23, 2010. The study showed that, in a group of 2,499 gay men, PrEP — in the form of a combination of drugs under the brand name Truvada — was 44 percent effective in preventing HIV seroconversion.

Under the guidance of Dr. Roy Gulick (director of the Weill Cornell Medical College HIV Clinical Trials Unit), a new experiment called the NEXT (Novel Explorations of Therapeutics) PrEP Study will begin this fall. It will include 400 at-risk, HIV-negative gay men, and will take place over 48 weeks at 12 sites across the U.S. and Puerto Rico.

The NEXT PrEP Study will differ from iPrEx in that its primary experimental group will receive a daily regimen of the drug maraviroc (brand name Selzentry). The control group will receive Truvada, and two other experimental groups will receive combinations of maraviroc and either tenofovir or FTC (the two individual drugs that make up Truvada). A major goal of the study, along with testing the HIV-prevention efficacy of maraviroc, will be to gauge the side effects of the drug on participants.

“The longest any HIV-negative person has taken PrEP in a clinical study is 12 weeks,” Gulick told Chelsea Now in a July 23 phone interview [This is actually a major factual error. For example, the average follow-up in iPrEx was 14 months - IRMA]. “Now, since this is a drug we’re giving to healthy people, the next step is exploring further to prove that it is both safe and tolerable for them.”

Read the rest 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.]

HIV Vaccine News

Recently, two new discoveries which may eventually lead to a vaccine for AIDS have been made by researchers. One, being presented at the IAS Conference in Rome this week, comes from the Maryland-based VirxSys Corporation. Researchers injected non-human primates with an altered form of SIV, the primate equivalent to HIV.

(Via CNN) Over the course of six months, five infected monkeys were injected with the vaccine three times, while five others were given a placebo vaccine. After 18 months, it was found that 40% of the vaccinated monkeys had very low to undetectable amounts of virus in their bodies.

“We are well on the path to a functional cure, at least in monkeys,” says Laurent Humeau, VirxSys vice president of research and development.

“Although this pre-clinical study is modest in terms of size, it is highly unusual to see near non-detectable levels of the virus not only circulating in the blood, but also in the reservoirs where HIV is known to replicate,” said Joep Lange, M.D., Ph.D., professor of medicine at the Academic Medical Center, University of Amsterdam, and head of the Amsterdam Institute of Global Health and Development.

In the monkeys, the vaccine’s effect was sustained two years after the initial vaccination, without the need for any booster shots.

Other researchers have created similar type therapeutic vaccines. In May, Dr. Louis Picker of the Oregon Health and Science University’s Vaccine and Gene Therapy Institute announced a vaccine successful in preventing monkeys from acquiring SIV. Like the VirxSys vaccine, this was a genetically altered virus. In this case, the altered virus was CMV, from the herpes family.

But making the leap from monkeys to humans is a big step. Therapeutic vaccines "have looked really good in monkeys – but monkeys are not people and SIV is not HIV," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease. "Really good concepts in primates have been duds in people.”


The other study, published last week, focused on antibodies which, if harnessed, could help the human body fight the HIV virus:

(Via US News) Researchers report that they've gained insight into the workings of the immune system's response to HIV, the AIDS virus, in certain people, potentially providing a boost as scientists work toward a vaccine.

The findings won't have an immediate big impact on either vaccine research or HIV treatment. However, they do reveal how soldiers of the immune system known as antibodies use special powers to combat the virus in some patients, said study co-author Dr. Michel C. Nussenzweig, a professor of immunology at The Rockefeller University in New York City.

Ultimately, he said, scientists could develop a vaccine that teaches people's bodies how to make the antibodies. "You'd try to make them do it themselves," he said, instead of pumping antibodies into the body.

Since the late 1990s, AIDS has largely become a treatable, chronic disease. But it can still be deadly, and many scientists think they're years away from developing a vaccine to prevent people from becoming infected in the first place.

In the new study, published online July 14 in Science, researchers focused on antibodies that are produced only in certain patients with HIV. They work by preventing the virus from picking the locks in cells that are supposed to keep germs out.

[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.]

PrEP: Prevention Revolution or Magical Thinking

One of the most exciting developments in the fight against HIV is a recent study that concluded that gay men could significantly reduce their risk of infection by taking an existing anti-HIV medication on a daily basis.


Earlier this month our friends at Feast of Fun and Lifelube hosted a forum in Chicago to discuss the iPrEx study published this winter. It was an energetic and exciting discussion with scientists, advocates, and real people taking the pill on the possibilities and concerns surrounding PrEP. For those too far or too busy to make it, Feast of Fun recorded the forum as a podcast, available for free on their website. Please check out the podcast and share your thoughts on the study.



Keith Green, Marc Felion, Dr. Bob Grant and Fausto Fernós - Forum Hosts and Participants


[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.]

Anti-AIDS Gel Also Boosts Sexual Pleasure

Via Times of India.

 South African scientists, who launched a 24-month trial to confirm the efficacy of a microbicide gel that would reduce the risk of women getting HIV, have found an unexpected spin-off – it also boosts sexual pleasure.

Wits professor Helen Rees, of the university's reproductive health and HIV institute, said the R300m trial would involve about 2,200 sexually active women at seven locations countrywide.

The Tenofovir gel study - known as Follow-on African Consortium for Tenofovir Studies (Facts) study - would be a follow-up to the Caprisa 004 study, which showed that a highly consistent use of the microbicide by women resulted in a 59 per cent reduction in the risk of HIV infection.

Rees said during a previous study involving another gel - that proved unsuccessful in the fight against HIV - participants had noted the gel improved their sexual pleasure.

"One of the big messages we got, was many women said 'We liked this', News24.com quoted her as saying. 

 

Read the rest 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.]