For Immediate Release
October 25, 2010
FDA and CONRAD Chart U.S. Regulatory Path for 1% Tenofovir Gel for
Collaborative meeting held with key stakeholders
Arlington, VA – – The U.S. Food and Drug Administration (FDA) held an end-of-Phase II
meeting to determine the next steps required for U.S. licensure of 1% tenofovir gel, a
microbicide product recently found to be effective at reducing the rate of HIV and herpes infection
in women when used before and after sex.
The meeting, held on October 20, 2010, was requested by CONRAD, a division of the Eastern
Virginia Medical School in Norfolk, VA. CONRAD was one of the partners in the Phase II
study, “CAPRISA 004,” which evaluated 1% tenofovir gel in prevention of male-to-female HIV
transmission in 889 women in South Africa. USAID provided funding for the trial, conducted
by the Centre for Programme Research for AIDS in South Africa and U.S. based FHI, which was
the first study to show that a vaginal gel can reduce the risk of HIV and herpes infection in
women. CONRAD manufactured and provided the tenofovir gel for the study.
Tenofovir gel was found to be 39% effective in reducing a woman’s risk of becoming infected
with HIV during sex and 51% effective in preventing genital herpes infections in the women
participating in the trial. Results of the CAPRISA 004 clinical trial were reported in July 2010
and represent the first “proof of concept” for a vaginal microbicide.
A number of key stakeholders contributed to the collaborative meeting with the FDA, including
representatives from the U.S. National Institutes of Health, the U.S. Agency for International
Development, Gilead Sciences, Microbicides Trial Network (MTN), South African clinical
investigators, the International Partnership for Microbicides (IPM) and FHI.
During the meeting, the FDA stated their preference for two well-controlled studies to verify the
safety and efficacy of 1% tenofovir gel prior to submission of a New Drug Application (NDA).
The FDA furthermore stated that the NIH-sponsored Phase IIB study, MTN-003, known as
VOICE (Vaginal and Oral Interventions to Control the Epidemic), represents a second adequate
and well-controlled study that would, if successful, serve as the second pivotal trial together with
CAPRISA 004 to support the submission of an NDA for 1% tenofovir gel.
In addition, the FDA has granted Fast Track approval designation for 1% tenofovir gel, which
facilitates the development and expedites the review of drugs that are intended for treating
serious diseases and fill an unmet medical need. With Fast Track designation, an NDA can be
submitted as a “rolling review”, which allows a clinical trial sponsor to submit completed
sections of its NDA for review by the FDA, rather than waiting until every section of the
application is completed before the entire application can be reviewed.
The agency agreed that the current preclinical program for 1% tenofovir gel is sufficient to
support a future NDA. However, they stated that additional safety data on adolescents would be
needed and that information on in vivo drug interaction studies with commonly used vaginal
products should be obtained. Also, the FDA will ultimately need data on post menopausal
women. It was also agreed that a future meeting with the FDA would be held to address any
outstanding discussions associated with product quality, including chemistry, manufacturing and
controls (CMC). Since much of the clinical work on 1% tenofovir gel has been and will be
conducted in South Africa, FDA officials indicated that they can work through the FDA’s
“Office of International Programs” with the goal of coordinating the data and review processes
with the South African Medicines Control Council.
CONRAD and its partners appreciate the contributions and detailed recommendations put forth
by the FDA, which have helped clarify the next steps required for testing and licensure of 1%
In 2006, CONRAD and IPM obtained a co-exclusive, royalty-free license from Gilead Sciences
to develop 1% tenofovir gel as a topical microbicide for use by women in developing countries
to prevent HIV.
For more information, please contact Annette Larkin, +1 703 772 6427 or
By Rod McCullom
July 22, 2010
Vienna, Austria — From pre-conference events to the massive human rights march through downtown Vienna, world leaders, public health experts and HIV activists honed in with laser-like precision on a common message at The 18th International AIDS Conference in Vienna : The ongoing persecution and criminalization of gay, bisexual and other men who have sex with men — “MSM”, in public health shorthand — are undermining efforts to control the global HIV/AIDS pandemic.
Chief among the obstacles: More than 80 nations have laws that still criminalize same sex behavior. In some of these countries, conviction can even result in the death penalty, reports UNAIDS.
Further exacerbating the problem, according to a report by Planned Parenthood, “58 countries have laws that criminalize HIV or use existing laws to prosecute people for transmitting the virus. Another 33 countries are considering similar legislation.’
The trend is “even more pronounced” across Africa and the Diaspora, said Joel Gustave Nana, executive director of the Johannesburg, South Africa-based African Men for Sexual Health and Rights (ASMSHer). The West African laws vary in extremity — just “exposing a person to HIV, regardless of if the virus is transmitted, is a crime in Benin, and Tanzanian law carries a possible sentence of life in prison for intentional transmission,” reports Medical News Today. While the overall life for Black MSM may be better for in North America, there are drawbacks. The United States and Canada lead the world when it comes to prosecuting people who infect or expose others to HIV, a surprising new study reveals. Black men have been disproportionately targeted with these prosecutions. A Black, gay, HIV positive Michigan man was recently as charged as a bioterrorist for allegedly biting a neighbor’s lip during a scuffle, Black AIDS Weekly reported in June.
“The prosecutions are arbitrary,” said Nana, in an interview after a press conference organized by The Global Forum on MSM & HIV. On Sunday, the day before the conference officially opened, the Global Forum held a 24-hour event to address the soaring global rates of MSM seroconversions.
“The stigma, discriminatory laws and criminalization of HIV transmission encourage the spread of this disease,” adds Nana. “Why should someone seek testing or medical advice come forward if you could be arrested? There is no incentive.”
“This is the context in which you have a runaway, dangerous HIV epidemic in Jamaica,” adds Robert Dr. Robert Carr, the co-chair of ICASO, the International Council of AIDS Service Organizations (ICASO). “There is a clear link between religious condemnation, criminalization, stigma and HIV infections. We see this all the time in the Caribbean.”
Carr adds: “Politicians and church leaders endorse homophobic violence. Police refuse to protect MSM or are complicit or directly involved in the violence,” he said, referring to a now-infamous incident of a 2,000-strong mob surrounding several gay men and stoning them. The police were called to the scene and the officers also struck the young men.
Carr sighs. “With Jamaican MSM infection rates at 32 or 33 percent, it became obvious that you couldn’t do effective HIV work in this context.”
“We now have 14 countries out of 54 that include men who have sex with men in their national HIV strategic plans,” AMSHer’s Joel Nana said. “It doesn’t mean the services will be delivered to those populations, but it is an acknowledgment. That’s a first step.”
“Kenya was the first African nation to include MSM in their national HIV strategy,” Nairobi-based peer educator Job Akuno told Black AIDS Weekly. Akuno is a counselor with the Nairobi-based SHAP, Scaling Up HIV and AIDS Prevention, partially funded by PEPFAR, the President’s Emergency Plan for AIDS Relief. “That was in 2006. But … it seems like we are rolling back on some of the gains that we made.”
“Kenya is starting to look like one of the countries that we should look up to,” Nana adds. “The HIV movement is more open to include MSM. And there is a strong MSM movement in Kenya, too . It is one of the few countries in Africa where a MSM organization was able to place an ad in the newspaper for the International Day Against Homophobia on May 17.”
Akuno says the HIV Prevention and Control Act criminalizes deliberate HIV transmission. “The sentences are up to 10 years. No one has been prosecuted, but now there is talk to make the law harsher. If you criminalize HIV transmission or only target MSM, that will further stigmatize the disease and drive many people into not wanting to know their results. ”
Job Akuno shrugs. “What can you do but hope for the best?”
Rod McCullom, a writer and television news producer, blogs on Black gay, lesbian, bisexual and transgender news and pop culture at rod20.com.
UNAIDS Recommended Components for
Comprehensive HIV Prevention Programs with MSM
1. Promotion and guarantee of human rights; removal of legal barriers that undermine access to HIV-related services such as laws that criminalize consensual sex between men;
2. Access to and promotion of consistent condom and water-based lubricant use;
3. Detection and management of sexually transmitted diseases;
4. Confidential, voluntary HIV screening, care, treatment and support services;
5. Safer drug-use commodities and treatment services;
6. Empowerment of gay, lesbian, bisexual and transgender communities to participate equally in social and political life;
7. Safe virtual and/or physical spaces for MSM to seek information and referrals for care and support;
8. Training and sensitization of health-care providers to avoid discriminating against MSM;
9. Medical and legal assistance for boys and men who experience sexual coercion and/or violence;
10. Specific and targeted information on prevention and risk reduction strategies designed to appeal to and meet the needs of MSM;
11. Information, prevention and care services for the female and transgender partners of MSM;
12. Prevention and treatment of hepatitis; and
13. Availability of HIV-related prevention information, care and support services for transgender people who may not identify as MSM.
• The imperative of reducing STD and HIV infection rates should not impinge on personal freedoms;
• All people, including MSM and MSM living with HIV, deserve the same level of support, health care, support services and political rights as anyone else;
• All people, including MSM and MSM living with HIV, are entitled to a fulfilling and satisfying sex life;
• All people, including MSM and MSM living with HIV, have the right to be self-determining;
• MSM, including MSM living with HIV, should be actively and meaningfully engaged at all stages and levels in research, program and policy development, implementation and evaluation—participatory processes should be utilized throughout;
• HIV prevention programs and services should not be risk or deficit oriented—instead successful HIV prevention efforts should leverage, and be rooted, in the strengths, resources, competencies, social connections, capacities, and resiliency that are already present in MSM individuals and communities;
• Pleasure, gender, satisfaction, intimacy, love, and desire are key concepts in a fuller understanding of sex and sexuality among MSM and therefore in formulating more meaningful research, programmatic, and policy responses; and
• Researchers, prevention practitioners, and policy makers should consider structural, situational, and contextual factors in understanding HIV risk and in developing sexual health interventions tailored to the specific needs of MSM.
Broader adoption of these principles will provide a common foundation for the ongoing development and promotion of effective, evidence-based HIV prevention and sexual health services that address the specific needs of MSM. Principles of practice can also bring balance to discussions about HIV prevention with and for MSM, discussions that too often take place without us.
20,21 The following are some important core principles of practice that can serve as broad guidelines in the design, implementation, and evaluation of targeted HIV prevention programs and paradigms within MSM communities worldwide:
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For more information, please contact us at +1.510.271.1950 or email@example.com
Balancing Evidence with Rights-based Principles of Practice
There has been a TON of press in the last few days stemming from the Microbicides 2010 conference regarding two new studies on the safety of lubricants used for anal sex.
Below is an excellent, non-hyperbolic story from Gus Cairns over at AIDSmap, and below that, IRMA’s press release plus the audio recording of the press conference where this information was presented to the media.
Following that is a note from Marc-André LeBlanc:
IRMA Steering Committee Member and Chief Lubricant Safety Expert
Next is a synopsis from our new report regarding IRMA priorities and activities regarding lube safety, and finally, a selection of the media coverage on this topic.
JUST ADDED 4:21 Central Time 5/27: Some Sexual Lubricants Linked to Increased Risk for Chlamydia, Gonorrhea, by Bob Roehr on Medscape – another good article
Dear IRMA members,
Imagine our excitement to see such an explosion of interest in lube safety!
As many of you know, this has been a core objective of IRMA’s work for 5 years, and one of the reasons we formed at all. The whole idea behind the huge survey we launched in 2007 was to obtain data that would allow the field of lube safety research to move forward. We published the results of the survey — to our knowledge the world’s largest survey on anal sex and lubes with nearly 9,000 partiicpants in over 100 countries — in our 2008 report Less Silence, More Science. And we are thrilled to report that the results have just been accepted for publication in a peer reviewed journal and should be available very soon. Watch this space!
We will send out a notice for an IRMA call very soon, where we will provide an overview of the studies announced at M2010 this week, provide background on research done so far, and discuss plan for future research. This will also provide all of us with an opportunity to discuss messaging in relation to rectal safety of lubes.
In the meantime, we will continue to share information as it becomes available. For instance, you can check IRMA’s lovely new report From Promise to Product for some background information — including section 2.11 for some background information on testing of lubes, and section 4.4 for a description of IRMA’s work in this area. The two sections are copied below for your reference.
It is truly wonderful to be poised for true progress on this critical issue and we welcome everyone’s thoughts and efforts!
IRMA Steering Committee Member and Chief Lubricant Safety Expert
Excerpts from report
What do we know about the rectal safety of sexual lubricants?
In addition to the studies released at M2010, a few others have assessed the relative safety of sexual lubricants, though not always looking at rectal safety specifically. These studies looked at:
* Using in vitro and mouse assays to determine cellular toxicity, increased risk of HSV-2 infection, and epithelial sloughing caused by lubricants
* Testing the osmolarity of lubricants
* Using slug mucosal irritation assays to evaluate mucosal irritation caused by lubricants
The question remains: what do all of these studies tell us? We’re not sure. We still don’t know what assays should be used to determine the rectal safety of lubricants. Furthermore, even when studies find a wide range of values for their safety markers, we still don’t know to what extent—if any—some of these markers might indicate a higher risk of HIV transmission.
Relatively high levels of cellular toxicity, mucosal irritation, cell damage caused by hyperosmolar or hypo-osmolar products, inflammation, or epithelial sloughing could in theory increase the risk of HIV infection. However, this remains to be proven.
* Some level of inflammation and irritation occurs naturally in rectal mucosa, even among healthy individuals;
* Anal intercourse itself, as well as enemas and douching, causes some transient damage; and
* Rectal epithelium regenerates quickly after minor damage or sloughing.
We must be able to compare normal levels of inflammation, irritation, cell damage and epithelial sloughing that occur among healthy individuals and those that are a result of AI. The question then becomes: does AI with lubes cause increased levels, similar levels, or lower levels of these markers compared to AI without lubes? Even if we were to find that some lubes cause higher levels of disruption, we would still need to investigate whether this translates into a higher risk for HIV transmission.
These questions remain to be answered, and we are still left with little data that can be translated into useful information that the public can use to make choices about lubricants. One thing to consider: if lubricants increase the use of condoms, that is probably a more important factor in preventing HIV transmission than any potential risk from lubes. For the moment, the use of lubes compatible with condoms is still considered to be an important risk-reduction tool for rectal transmission of HIV, and is likely to remain so. One day we may have valuable information on the relative safety of different lubricants, allowing users to make better informed decisions about which products they use.
IRMA’s advocacy on the safety of lubricants used for anal sex
Many men and women use sexual lubricants during AI, yet we know very little about the relative safety of these lubes. Obtaining safety data on products used as sexual lubricants for anal sex would be valuable for public health reasons.
Accordingly, IRMA prioritises advocacy for data collection on the rectal safety of lubricants. Wholly absent in current HIV prevention activities, a translation of this type of data into useful information for users, funders, programme directors, and policy makers would be of significant benefit to the field. Lessons learned in this undertaking will also provide valuable insights into message development on the safety and efficacy of vaginal and rectal microbicides, when these products become available.
Due to the paucity of this type of information, IRMA launched a global web-based survey in 2007 (see an overview of the results from this survey in IRMA’s previous report: Less Silence, More Science: Advocacy to Make Rectal Microbicides a Reality). The survey provided valuable information on lube use, preferences, and acceptability among nearly 9,000 men and women from over 100 countries, establishing a prioritised list of the most widely-used lubes to test for rectal safety.
A working group comprised of advocates and researchers was convened by IRMA to discuss the feasibility of testing sexual lubricants for rectal safety. While the working group identified significant scientific challenges that remain unaddressed to this day, there has been some progress.
IRMA’s action on lubricant safety includes the following activities:
* Encouraging researchers to test lubes for rectal safety and to share their findings;
* Facilitating dialogue among leading researchers and advocates within the working group on rectal safety of lubricants;
* Compiling articles and studies related to lube safety, particularly for rectal use, and maintaining an updated background document on this issue;
* Making IRMA’s list of most widely-used lubes available to anyone interested in testing lubes; and
* Keeping IRMA membership updated on developments in this area.
- Use of lubricants with anal sex could increase risk of HIV – Physorg.com
- Lubricant Use May Raise HIV Infection Risk During Anal Sex – MSN
- Risk of sexually transmitted disease three times higher when lubricant used with anal sex – Times LIVe Blog (South Africa)
- Use of lubricants with anal sex could increase risk of HIV – Armenian Medical Network
- Use of lubricants with anal sex could increase risk of HIV – Science Blog
- Unprotected anal sex ups HIV risk 20-fold – Thaindian News
- So Now Anal Lube Increases Your Risk of Getting HIV? – Queerty
- Lubricants for Anal Sex May Increase Risk of HIV, STIs – POZ
- Lubricant Use May Raise HIV Infection Risk During Anal Sex – U.s. News and World Report
- Lubricant Use May Raise HIV Infection Risk During Anal Sex – Bloomberg Business Week
- Unprotected anal sex ups HIV risk 20-fold – Sify News
- Currently Available Lubricants Used For Anal Sex May Actually Make It Easier For HIV To Be Transmitted – Medical News Today
- Lubricants may increase disease risk of anal sex, studies show – Los Angeles Times
- Lube May Make Anal Sex More Risky – Gawker
- Use of lubricants with anal sex could increase risk of HIV – HIV Atlas
- Use of Lubricants With Anal Sex Could Increase Risk of HIV – Science Daily
- IRMA: Research on lubricant safety very past due – Physorg.com
- Lubricant Use May Raise HIV Infection Risk During Anal Sex – Yahoo News
- Use of lubricants with anal sex could increase risk of HIV – e!Science News
- Lubricant Use May Raise HIV Infection Risk During Anal Sex – MedicineNet.com
- Why it is important to give that lubricant a second look – Africa Science News Service
- Anal sex studies from Microbicides conference show increased HIV transmission risk with some lubes – Examiner.com
- Lubricant use with anal sex may raise HIV risk – DNA India