International Study Finds High Levels of Adherence to Use of Rectal Microbicide Gel

Participants as adherent to using gel with sex as taking a daily pill for HIV prevention

CHICAGO, October 20, 2016 – Participants enrolled in a rectal microbicide study were just as likely to follow through using an anti-HIV gel with anal sex as they were to using daily oral pre-exposure prophylaxis (PrEP), according to adherence results presented today at the HIV Research for Prevention conference (HIVR4P). The study, led by the U.S. National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN), was the first extended safety study of a rectal microbicide for prevention of HIV infection from anal sex, which initially reported that the gel was safe in February 2016.

The Phase II study, MTN-017, began in September 2013 and enrolled 195 men who have sex with men (MSM) and transgender women at sites in Peru, Thailand, South Africa and the United States, including Puerto Rico. MTN-017 participants –12 percent of whom were transgender women – cycled through three study regimens which each lasted eight weeks: reduced glycerin tenofovir gel used daily, reduced glycerin tenofovir gel used before and after anal sex, and daily use of the antiretroviral tablet Truvada® (emtricitabine/tenofovir disoproxil fumarate) as PrEP, developed by Gilead Sciences, Inc.

Researchers found that most participants were highly adherent during the course of MTN-017, using study products 80 percent of the time or more. Participants were similarly adherent to using gel before and after sex (93 percent) as they were to taking daily oral Truvada (94 percent). They were less adherent when using the gel on a daily basis (83 percent).

“Overall adherence to the three regimens in MTN-017 was high,” said Alex Carballo-Diéguez, Ph.D., HIVR4P abstract co-author and professor of medical psychology, Columbia University. “What we found most remarkable was that even though efficacy of the gel has not been established, its adherence was similar to oral Truvada, which we know is effective. This tells us that rectal microbicide gels, provided they are proven effective, could be a potential alternative for people who don’t want to use daily oral PrEP.”

Adherence in MTN-017 was measured by a combination of responses to daily questions sent by text message, number of returned gel applicators, and blood tests to confirm the presence or absence of drug. Throughout the study, researchers employed real-time pharmacokinetics (PK), in which they regularly tested participants’ blood to assess the presence of drug – a determinant of whether they were using their assigned study products – and shared the results with participants as part of their adherence counseling sessions. These sessions also included convergence interviews, collaborative conversations to engage participants and clarify discrepancies among adherence measures.

In a related HIVR4P poster session (P24.11), Iván C. Balán, Ph.D., assistant professor of clinical psychology, Columbia University, found that convergence interviews conducted in MTN-017, which were aimed at improving the accuracy of adherence data, were feasible and acceptable to both adherence counselors and study participants. They also provided important context to understanding discrepancies in product use assessments and PK results. Engaging study participants as allies in the process was critical to avoid making them feel confronted and thus becoming defensive, noted Dr. Balán.

In addition to Dr. Carballo-Diéguez, abstract co-authors include Dr. Balán, Rebecca Giguere, M.P.H., Curtis Dolezal, Ph.D., Cheng-Shiun Leu, Ph.D., William Brown III, Ph.D., Titcha Ho, Ph.D., Camagu Tuswa-Haynes, M.S., all with the New York State Psychiatric Institute and Columbia University; Javier Lama, M.D., IMPACTA PERU Clinical Trials Unit; Jeanna Piper, M.D., Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID) at the NIH; Barbra Richardson, Ph.D., University of Washington and Fred Hutchinson Cancer Research Center; Ian McGowan, M.D., Ph.D., University of Pittsburgh; and Ross Cranston, M.D., Microbicide Trials Network.

Dr. Cranston is protocol chair of MTN-017 and Dr. Lama is protocol co-chair.

MTN-017 was funded by NIAID and the National Institute of Mental Health, both components of the NIH. Tenofovir gel was developed by Gilead Sciences, Inc., of Foster City, Calif., which assigned the rights for tenofovir gel to CONRAD, of Arlington, Va., and the International Partnership for Microbicides of Silver Spring, Md., in December 2006. Clinical input and study supplies of reduced glycerin tenofovir gel were provided by CONRAD, with funding from USAID.

# # #

Dr. Carballo-Diéguez’s abstract (QA20.01) is part of the HIV R4P oral presentation session Trust But Verify: Understanding Adherence taking place from 10:30-noon CDT, Wed., October 20. It is one of 22 MTN abstracts being presented at the HIVR4P 2016 conference. Webcasts of all HIVR4P 2016 sessions, along with the conference program and more information on the meeting is available at hivr4p.org.

More information and materials about MTN-017 and rectal microbicides are available athttp://www.mtnstopshiv.org/news/studies/mtn017.



About the Microbicide Trials Network

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 whose work is focused on the development and rigorous evaluation of promising microbicides – products applied inside the vagina or rectum that are intended to prevent the sexual transmission of HIV – from the earliest phases of clinical study to large-scale trials that support potential licensure of these products for widespread use. More information about the MTN is available at www.mtnstopshiv.org.

MTN is funded by the U.S. National Institutes of Health grants UM1AI068633, UM1AI068615 and UM1AI106707.

Click here for PDF version of this document.

News From the 2016 International AIDS Conference

The 21st International AIDS Conference in Durban, South Africa (AIDS 2016), held July 18 to 22, featured numerous pivotal presentations on HIV science. Conference goers absorbed cutting-edge information about antiretrovirals (ARVs), including treatment for the virus, treatment as prevention (TasP) and pre-exposure prophylaxis (PrEP), as well as the effort to test and treat the global HIV population, HIV among women, and the search for a vaccine and a cure.

Below is a recap of the major scientific findings presented at the conference. To read more about any of these studies, click the hyperlinks. To see a newsfeed of all AIDS 2016 reporting from POZ, click here or on the #AIDS2016 hashtag at the bottom of any article, including this one.

Vaccine:

Following a pilot study’s promising findings of an HIV vaccine’s ability to spur the immune system, researchers intend to begin enrolling participants into the Phase IIb/III HVTN 702 vaccine trial in southern Africa this fall. This will be the seventh major HIV vaccine efficacy trial. The vaccine under investigation is a retooled version of the one that in 2009 showed some success in preventing HIV among Thai participants.

Long-Acting HIV Treatment:

A long-acting injectable version of the ARVs cabotegravir and Edurant (rilpivirine), dosed every four weeks, will enter Phase III trials during the latter half of 2016, with initial results coming two years later. The Phase IIb LATTE-2 trial tested injections of the treatment given every four and eight weeks and found that the more frequent dosing schedule suppressed HIV more effectively.

Treatment as Prevention (TasP):

Three major studies underlined the considerable power of HIV treatment to prevent the spread of the virus, adding greater scientific heft to the notion that it may in fact be impossible to transmit HIV with a fully suppressed viral load.

In 2011, interim results from the HPTN 052 trial found that starting HIV treatment early rather than delaying was associated with a 96 percent reduced risk of transmission among mixed-HIV-status heterosexual couples. Now, final results from the study have showed that there were no transmissions within couples when the HIV-positive member was on ARVs and had a fully suppressed virus.

Interim results from the PARTNER study, which included both heterosexual and male-male mixed-HIV-status couples, also found no transmissions between partners when the virus was fully suppressed.

Also, the Partners PrEP study examined the effect of providing mixed-HIV-status heterosexual couples Truvada (tenofovir/emtricitabine) as pre-exposure prophylaxis (PrEP) for the HIV-negative partner as a “bridge” to the HIV-positive partner being on ARVs for at least six months. This protocol slashed HIV risk by 95 percent.

PrEP:

Gilead Sciences, manufacturer of Truvada, conducted an analysis of data from 80 percent of U.S. retail pharmacies and found that nearly 80,000 people had filled at least one prescription for the drug’s use as PrEP between January 2012 and December 2015. (If all sources of PrEP prescriptions could be accounted for, this number would likely be quite a bit greater.) Between the fourth quarters of 2012 and 2015, quarterly new PrEP prescriptions rose 738 percent, from 1,671 to 14,000, largely among men. This upward trend shows no signs of abating.

The IPERGAY study of an intercourse-based PrEP dosing protocol among men who have sex with men (MSM) in France and Canada found that the participants used condoms less frequently after they shifted from the trial’s placebo-controlled phase to its open-label portion in which everyone knew they were receiving Truvada. Despite such a shift in sexual risk taking, the men’s HIV rate was low during the open-label phase. The study’s researchers believe they now have enough evidence to support the notion that the dosing protocol itself was indeed responsible for reducing the risk of HIV among the men, rather than the mere fact that men were on average taking Truvada about four times a week. (Previous research has shown that taking Truvada that often offers maximum protection.)

Researchers found that teenagers given PrEP may need monthly monitoring to adhere well to a daily Truvada regimen. (PrEP is not currently approved for minors in the United States, and current guidelines stipulate monitoring every three months.) A separate studyfound that Truvada-related bone loss is reversible after young men stop PrEP and that the drug was not associated with fractures during the study’s follow-up period.

Another study found that among black MSM receiving PrEP, men were more likely to adhere to the regimen if they were older than 25, had more than a two-year advanced degree, did not use multiple medications that they were not prescribed and had a primary partner.

Women:

A follow-up of the previously reported MTN-020/ASPIRE study of an ARV-containing vaginal ring found that HIV-negative women who used the monthly ring well had a 56 percent reduced risk of contracting the virus compared with women receiving a placebo ring. Those who used the ring at the highest level cut their HIV risk by 75 percent or greater.

Two studies provided excellent news regarding the prevention of mother-to-child transmission of HIV. A nationally representative study found that just 4 percent of children born to HIV-positive women in South Africa contracted the virus by 18 months of age. Another trial found that HIV treatment could practically halt the transmission of HIV through breast feeding.

A collection of three studies provided new insight into why HIV rates among young women in South Africa are so high. In one study, researchers found that HIV transmission among adolescent girls and young women is driven by their sexual relations with men who are an average of eight years older. Two other studies suggest that particular bacteria in women’s vaginas may facilitate transmission.

Cure:

Researchers have developed a consortium to help develop and study stem-cell transplant cures for HIV that would replicate the success of the pair of such transplants that cured the famed Berlin Patient while also treating his leukemia. They already have a few transplant recipients who, while still taking HIV treatment, show very small amounts of the virus in their viral reservoirs. These individuals would need to stop taking ARVs for researchers to determine whether they may have been cured of the virus.

A study found that treating HIV within 15 days of infection prevented the development of antibodies to the virus among a group of South African women. Such early treatment also preserved their immune function. The study’s ethics committee believes the women should remain on treatment for two to three years before researchers may discuss with the participants the possibility of taking them off treatment to see whether the virus rebounds.

On the subject of viral rebound after a treatment interruption, an experimental treatment with the HDAC inhibitor (a kind of cancer drug) vorinostat, the immunosuppressant hydroxychloroquine and the ARV Selzentry (maraviroc) had no effect on viral rebound after an HIV treatment interruption.

90-90-90:

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has called for, by 2020, getting 90 percent of the world’s HIV population diagnosed, 90 percent of that group on treatment for the virus, and 90 percent of that group virally suppressed. Achieving the 90-90-90 targets would mean that, of all people living with the virus, 90 percent would know their status, 81 percent would be treated and 73 percent would be virally suppressed.

Research suggests that nations are advancing toward these targets, with 17 million people on treatment in 2015. One intervention in particular has surpassed the targets in certain rural Ugandan and Kenyan communities. But UNAIDS executive director Michel Sidibé raised serious concerns at AIDS 2016 that a retreat of major donor commitments from paying for HIV care and treatment worldwide could stymie such progress.

An analysis of spending by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) found that foreign aid dollars go disproportionately to epidemics more generalized across a national population than to those concentrated among MSM or injection drug users (IDUs).

In another wrinkle, the first major study of the public-health effects of programs to aggressively test and treat HIV found that, in South African communities receiving such an intervention, providing immediate treatment rather than following national guidelines was not associated with any difference in the rate of new HIV cases.

HOPE for the Vaginal Ring: Follow-Up Studies on New HIV-Prevention Method for Women Announced

More than 300 members of the Microbicide Trials Network (MTN) were gathered in a hotel conference room in Rockville, Maryland, earlier this month and, somewhat unexpectedly, the assembled scientists had something to celebrate. On March 13, four days after the National Institutes of Health (NIH) convened a stakeholder meeting of African women, researchers, advocates and statisticians, it announced that it would indeed fund follow-up studies to the ASPIRE dapivirine (TMC120) antiretroviral ring trial.

The results of ASPIRE and its sister trial, The Ring Study, were released during CROI 2016 at the end of February. Then, this month the NIH held its meeting. When Sharon Hillier, Ph.D., one of ASPIRE's principal investigators, announced the results to MTN staff, "people literally cheered -- they just stood up and cheered," she said.

That's because, after many attempts and several disappointing trial results, this was one of the few microbicide trials -- and one of the fewer designed specifically for women -- to move on to open-label extension trials and potentially lead to availability for those women who need HIV prevention most.

"Everyone is so anxious to take this next step, to see -- can we realize the promise we think we have [with the ring]? And can we build on this to do even better?" she said. "No one is happy with 27% [overall effectiveness rate]. And we think we can do better than 27%."

ASPIRE and HOPE

When ASPIRE's results came out at CROI 2016 last month for the dapivirine ring, the 27% reduction in HIV acquisition sounded modest to say the least.

But, when researchers parsed the data further, they discovered that efficacy went up with a woman's age. For women aged 21 and under, the ring provided no benefit. For women 21 to 25, effectiveness shot up to 56%. For women older than that, the rate was 61%.

That 61% was the foundation for moving forward with additional studies, said Anthony Fauci, M.D., director of the NIH's National Institute of Allergy and Infectious Disease.

"Everyone went in to the [NIH] meeting saying, 'We need to first examine the data -- is there really a pathway forward?'" he said. "It's clear there is, even though it's confusing when you look at the data. Twenty-seven percent is rather weak, but when you break it down by women older than 25 and women younger than 21, the 61 percent effectiveness is good enough to move forward. That's as good as circumcision in some respects."

Specifically, the NIH funded two follow up studies. One, ASPIRE's open-label extension trial, named HOPE, will seek to recreate the first study, but with some twists. Each of the 2,629 women in Malawi, South Africa, Zimbabwe and Uganda who participated in the original trial will be offered the dapivirine ring. The hope, said Fauci, is that if women know that they are getting a ring with active drug in it and that it's been proven to reduce HIV acquisition, then more women will use the ring, which may change overall protection rates. It's happened before.

However, the study will also tackle adherence another way: by asking the women to once again consent to the study, but this time also asking them candidly whether they're participating in the study because they really want to reduce their risk for HIV, or whether the study is the only way for them to get regular sexual and reproductive health care.

"By re-consenting them, we're saying, 'We get it,'" he said. "'So tell you what: Sign up for the study, but be honest, tell us if you have any intention or not of using the ring.' So then they'll be able to separate out the people who are really using it from those who aren't."

Study participants who say they don't intend to use the ring will still receive health care, but their intention not to adhere will be factored into results.

Then, the study will check in with participants every month for three months, changing out the ring and checking how much less dapivirine is in it after 30 days than when it was distributed -- a sign that participants have actually used it. The idea is to remove the incentive to lie to get health care and use drug levels to test for adherence.

Finally, the study will have a divided design: In those first three months, participants will come to the clinic every month to get a new ring. For the second three months, participants will be given a pack of three rings and be instructed to change the ring out themselves. Then, participants will be asked to bring back the rings, and total drug depletion will be measured.

"It's clever," Fauci said. "It will give [researchers] a chance to compare a clinical trial setting, where [women] are seen every month, versus a real-world setting, where we give them three rings. The bottom line is to figure out what role adherence plays in efficacy and what are the motives to participate."

Robust Discussion

Dazon Dixon Diallo, president and founder of SisterLove, Inc., and convener of the U.S. Women and PrEP (Pre-Exposure Prophylaxis) Working Group, was at the NIH meeting and described it as a robust discussion of both the science and women's reproductive health needs.

Unlike the VOICE trial, which was designed to test the ability of combination tenofovir/emtricitabine (Truvada) to prevent HIV in women, but was stopped early due to lack of adherence, there was no effort to blame participants for not using the drug. The question was, "How do we design these trials in a way that does not design it to fit the research, but is also meant to fit into women's lives?"

"It was not about blaming them," Dixon Diallo said. "It was really looking at the full implications of a large clinical trial like this, and how nimble can it be to really understand and shift as needed to make sure that the trial itself is fitting into women's lives in such a way that makes them want to be more adherent and to participate."

In particular, she pointed to the comment of one 18-year-old participant, who had asked the ages of the counselors who worked with women during the trials. The implication, said Dixon Diallo, was that mixing peer support and relatable staff could improve social connections and change how younger women, especially, perceive the trials.

For her part, Hillier said that the NIH's decision to fund the studies was not just a win for ASPIRE, but also for the technology in general, which will receive follow up separately in The Ring Study.

"With these two positive results in two separate studies, if [the NIH] didn't move forward, it was really closing the book on this kind of research," Hillier said. But now, she said, everyone on the team is excited about next steps. "We're feeling like we have a ton of work to do, but we're really excited we get to do it."

What a Young Woman Wants

When the NIH announced its funding of HOPE, it also announced funding for another trial, one meant to ask a different question: Why did the dapivirine ring show no effectiveness in women under 21, the group of women at highest risk for HIV?

It could be that younger women weren't using the ring. But it could also be that there's something biologically different about young women that makes the dapivirine ring ineffective. So MTN-035, also funded by the NIH this month, will seek to determine if it's preference or biology.

The 18-month study will be divided into three sections. For the first six months, women will get to choose either tenofovir/emtricitabine pills or the dapivirine ring for HIV protection. For the next six months, they will switch. Then, at the end of the year, they will be asked which method they prefer -- "or neither, obviously," Hillier added.

At the same time, when women attend their monthly clinic visits, researchers will take biological samples -- vaginal fluid samples, for instance, or swabs -- to study the immune cells in the vagina and other biomarkers of HIV risk. That data will be broken down further into very young women aged 16 to 17 and women 18 to 21, to assess whether biological markers and efficacy differ by prevention type.

"So we're trying to give women a sense of agency," said Hillier, "that they're going to be empowered to select what works for them."

Heather Boerner is a health care journalist based in San Francisco and author of Positively Negative: Love, Pregnancy and Science's Surprising Victory Over HIV.

Gay Men and Trans Women Adhere Well to Rectal Gel As PrEP in Early US Study

A rectal gel containing 1 percent tenofovir showed promise as pre-exposure prophylaxis (PrEP) against HIV in a group of transgender women and men who have sex with men (MSM), who adhered well to the protocol for the gel’s use. The Phase II MTN-017 trial included 187 MSM and trans women in sites in the United States, (including Puerto Rico), Peru, Thailand and South Africa. Results were presented at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

Tenofovir-infused topical gel has protected non-human primates and successfully combats HIV in laboratory tests. Previous research has found that a vaginal formulation of 1 percent tenofovir was neither safe nor acceptable in the rectum. So the gel in this study was one that had been reformulated into a reduced glycerin formation of 1 percent tenofovir gel.

The participants for this study, all of whom reported receptive anal intercourse, were randomized so that each went through three phases of the trial, but in different orders. These phases included eight weeks each of the following (with a one-week “wash-out” period between each phase): the rectal 1 percent tenofovir gel with instructions to insert it into the rectum daily; the gel with instructions to use it rectally before and after anal intercourse, or at least twice weekly in the event of no receptive anal intercourse; or Truvada (tenofovir/emtricitabine) with instructions to take the tablet orally once daily. The study lasted for 27 weeks.

The participants, 12 percent of whom identified as women or transgender, made study visits every four weeks. The researchers measured the participants’ adherence to the various forms of PrEP through daily SMS texts as well as through returns of the product at each study visit (to see how much unused PrEP remained). They also tested study members’ plasma tenofovir levels at each study visit and gave them the results of that test at the subsequent visit. High adherence was defined as taking greater than 80 percent of expected doses.

There were no differences between the three versions of PrEP in terms of grade 2 adverse health problems. The researchers concluded that the rectal gel was safe in either of the dosing protocols.

Overall, the participants preferred the oral regimen to the two rectal application protocols, in particular the daily regimen. Ninety percent of individuals said they like liked the oral regimen, 80 percent liked the dosing protocol associated with sexual activity, and 70 percent liked the daily rectal gel protocol.

Adherence was generally high, and participants adhered similarly to administering the gel at least twice weekly and taking Truvada daily.

The researchers concluded that the trial supported further study of rectal microbicides in MSM and trans women, and that research should focus on convenient dosing regimens.

To read the conference abstract, click here.

International Study Finds Rectal Microbicide Gel Safe When Used Daily and With Sex

Participants as adherent to using gel with sex as taking a daily pill for HIV prevention

BOSTON, February 24, 2016 – A reduced glycerin formulation of tenofovir gel was found safe when used daily and around the time of sex, according to the first extended safety study of arectal microbicide for HIV prevention from anal sex. Presented today at the 23rd Conference on Retroviruses and Opportunistic Infections (CROI 2016), the study, led by the U.S. National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN), also indicated that participants were as likely to follow through using the gel with sex as they were to using daily oral pre-exposure prophylaxis (PrEP) – a prevention strategy in which people who are HIV-uninfected take a daily pill to reduce their risk of infection.

The Phase II study, MTN-017, began in September 2013 and enrolled 195 men who have sex with men (MSM) and transgender women at sites in Peru, Thailand, South Africa and the United States, including Puerto Rico. MTN-017 participants –12 percent of whom were transgender women – cycled through three study regimens which each lasted eight weeks: reduced glycerin tenofovir gel used daily, reduced glycerin tenofovir gel used before and after anal sex, and daily use of the antiretroviral tablet Truvada® (emtricitabine/tenofovir disoproxil fumarate), developed by Gilead Sciences, Inc. This design allowed researchers to collect information about the gel’s safety and acceptability in the rectum, and compare it to the use of oral Truvada, which was approved for use as PrEP by the U.S. Food and Drug Administration in 2012.

Most side effects from study products in MTN-017 were minor, indicating the gel was safe, and there were no significant differences in adverse events among the gel regimens compared to oral Truvada. Overall, participants were highly adherent in MTN-017, with most following through in using their assigned products 80 percent of the time or more. Participants were similarly adherent to using gel before and after sex (93 percent) as they were to taking daily oral Truvada (94 percent). They were less adherent, however, when using the gel on a daily basis (83 percent). Adherence in MTN-017 was measured by a combination of responses to daily questions sent by text message, number of returned gel applicators and blood tests to confirm the presence or absence of drug.

When asked about preferences, participants reported they preferred oral Truvada to the gel, but found the before and after sex gel regimen as easy to use as oral Truvada. When asked about the likelihood that they would use the study products in the future, participants said that they would be as likely to use the gel before and after sex as they would to take oral Truvada. Forthcoming analyses from MTN-017 will shed light on how much drug was absorbed in the blood, rectal fluid and tissue, and assess whether use of the products caused changes in cells or tissue.

“The results from MTN-017 demonstrate there is a place for rectal microbicides used around the time of sex in future HIV prevention efforts,” said Ross D. Cranston, M.D., associate professor, University of Pittsburgh School of Medicine, who led the study with Javier R. Lama, M.D., M.P.H., investigator and director, HIV Prevention

Intervention Studies, IMPACTA PERU Clinical Trials Unit, Lima, Peru. “While we have more to learn from ongoing analyses of tissue and blood testing, the completion of this study was a significant undertaking and represents a major step forward in the development of a rectal microbicide for people at risk of HIV from anal sex.”

MTN-017 was a larger follow-up trial to a previous study, MTN-007, that found the reduced glycerin formulation of tenofovir gel was safe and acceptable to both men and women who used it in the rectum daily for a one-week period. The gel used in both studies was formulated with less glycerin to address gastrointestinal side effects experienced by some study participants who used an original vaginal formulation of tenofovir gel in an early study called RMP-02/MTN-006.

“The MTN-017 findings come at a pivotal time in the field of rectal microbicides, setting the stage for future studies and complementing ongoing research into new products and delivery methods,” said Ian McGowan, M.D., Ph.D., principal investigator of the MTN and professor of medicine, Division of Gastroenterology, Hepatology and Nutrition and Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine. “Research is already underway at MTN to expand the pipeline of rectal microbicide products in order to find the right product to move forward into an effectiveness study.”

Globally, racial and ethnic minorities, MSM and transgender women are disproportionately affected by HIV. Although most microbicide research has focused on products for vaginal use, the risk of becoming infected with HIV from unprotected anal sex may be 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.

In addition to Drs. Cranston, Lama and McGowan, co-authors include Alex Carballo-Dieguez, Ph.D., Columbia University; Cindy Jacobson, Pharm.D., MTN; Sherri Johnson, FHI 360; Ratiya Kunjara Na Ayudhya, BSMT, MTN; Mark Marzinke, Ph.D., Johns Hopkins University; Jeanna Piper, M.D., Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID); and Barbra Richardson, Ph.D., University of Washington and Fred Hutchinson Cancer Research Center.

MTN-017 is funded by NIAID and the National Institute of Mental Health, both components of the NIH. Tenofovir gel was developed by Gilead Sciences, Inc., of Foster City, Calif., which assigned the rights for tenofovir gel to CONRAD, of Arlington, Va ., and the International Partnership for Microbicides of Silver Spring, Md., in December 2006. Clinical input and study supplies of reduced glycerin tenofovir gel were provided by CONRAD, with funding from USAID.

# # #

More information and materials about MTN-017 and rectal microbicides are available athttp://www.mtnstopshiv.org/news/studies/mtn017.

About the Microbicide Trials Network

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 whose work is focused on the development and rigorous evaluation of promising microbicides – products applied inside the vagina or rectum that are intended to prevent the sexual transmission of HIV – from the earliest phases of clinical study to large-scale trials that support potential licensure of these products for widespread use. More information about the MTN is available at www.mtnstopshiv.org.

Click here for PDF version of this document.

Tobacco plant be the key to HIV Prevention via Microbicidal Gel?

HSC communications and marketing

Researchers from the University of Louisville will lead an international effort to utilize tobacco plants to develop a gel containing a specific protein that will prevent the transmission of HIV. The project is being funded by a five-year, $14.7 million grant from the National Institutes of Health.

Kenneth Palmer, PhD, is leading research into using tobacco plants to help develop a gel that would prevent HIV.


“Our researchers are looking to solve problems that affect the world,” James Ramsey, president of the University of Louisville, said during an announcement of the research Aug. 4. “Globally, more than 34 million people are HIV positive. The development of a low-cost method to prevent transmission of HIV certainly is something that is desperately needed and the use of tobacco plants as a method of carrying the vaccine appears to be key in the process.”

“Approximately seven years ago, UofL and Owensboro Health created a joint venture to develop a world-class plant pharmaceutical program that would have an impact globally,” said David L. Dunn, MD, executive vice president for health affairs at UofL. “Today’s announcement, coupled with the announcement we made in May about the Helmsley Charitable Trust providing funding to our research into two other cancer vaccines utilizing tobacco plants, demonstrates that the vision is becoming a reality.”

Kenneth Palmer, Ph.D., professor of pharmacology and toxicology and director of theOwensboro Cancer Research Program of UofL’s James Graham Brown Cancer Center, is leading a team of researchers from the University of Pittsburgh, the Magee-Women’s Research Institute in Pittsburgh, the Centers for Disease Control and Prevention, Karolinska Institutet in Stockholm, Sweden, the University of Manitoba in Winnipeg, Canada, the University of Maryland, Baltimore and Kentucky Bioprocessing Inc. and Intrucept Biomedicine LLC in Owensboro.

The team is working with the carbohydrate combining protein Griffithsin (GRFT), which is found in red algae. In laboratory work, the protein has shown to have broad-spectrum activity against HIV. GRFT binds to the dense shield of sugars that surrounds HIV cells and prevents these cells from entering other non-HIV cells. The team plans to develop a gel containing the protein for use during sexual intercourse by people at risk for HIV transmission.

To develop the microbicide, Palmer’s team takes a synthetic copy of the protein and injects it into a tobacco mosaic virus, which carries the protein into the tobacco leaves. After 12 days, the researchers harvest the leaves and extract the mass-produced protein for development into the vaccine.

“Our goal is to optimize the delivery system of the protective agent, which in this case is a gel, and determine its safety and estimates of its efficacy, leading to a first-in-humans clinical trial,” Palmer said.

“People may question why a cancer program is conducting research into HIV prevention,” said Donald Miller, MD, director of the James Graham Brown Cancer Center, a part of KentuckyOne Health. “In fact, cancer can be a result of every major disease that we know about, and HIV infection is no exception.”

Overall, the grant contains three significant projects – The Critical Path Project; Preclinical Testing Project; and Clinical Trial Project.

The critical path project involves manufacturing the microbicide active ingredient, ensuring quality of the microbicide and the formulated gel product and production for actual use. This process is in collaboration with two Owensboro-based biotechnology companies (Kentucky Bioprocessing Inc. and Intrucept Biomedicine LLC), and Lisa Rohan, PhD, at the University of Pittsburgh and Magee-Women’s Research Institute. Rohan has significant experience developing delivery systems for similar medications.

The preclinical testing project is a collaboration with the Centers for Disease Control and Prevention in Atlanta to use an animal model to ensure that the vaccine is safe and to determine that it actually provides protection from infection.

The clinical trial project involves developing the application to conduct a clinical trial for the Food and Drug Administration, as well as conducting the first-in-humans testing.

Alarm rings on low uptake of existing prevention options for anal STIs and HIV

Despite overall progress in HIV prevention, rates of HIV infection among key affected populations such as men who have sex with men (MSM) and transgender people remain alarmingly high. For example, recent data indicates that MSM are up to 19 times more likely to have HIV than the general population – transgender women are almost 50 times more likely. Overall new HIV infection rates have dipped by 26% in Asia and the Pacific region since 2001,but not for MSM and transgender.

According to a 2013 UNAIDS report, estimated population of MSM in the region is between 10.5 million to 27 million. HIV incidence continues to remain very high among MSM in cities such as Bangkok, Ho Chi Minh City, Jakarta among others.

(L-R) Dr I Gilada, Midnight P,Dr V Chakrapani, Dr Suwat C Midnight Poonkasetwattana, Executive Director of Asia Pacific Coalition on Male Sexual Health (APCOM) addressed a press conference jointly organized at 20th International AIDS Conference (AIDS 2014) by AIDS Society of India, APCOM, AVAC - Global Advocacy for HIV Prevention, Citizen News Service (CNS), International Rectal Microbicide Advocates (IRMA) and Research Institute for Health Sciences (RIHES), Chiang Mai University.

Midnight said: "Key affected communities should be in the heart of the delivery of services by the government, then only perhaps the impact will be maximal. Commission on AIDS in Asia (2008) had predicted that if no action was taken to increase the investment to MSM programming then they will account for nearly 50% of new HIV infections by 2020. That is a cause of serious concern. Punitive laws and practices that criminalize same-sex behaviour are still prevalent in many Asia Pacific countries. Such laws deter MSM and transgender people to have access to existing health services they need. We need to work on destigmatisation of healthcare services, and working with the law enforcers for supportive health policies. At policy level we need to advocate with the government, we need to ensure that policy barriers get removed so that MSM can actually access those services."

Investment continues to remain very low in MSM programming. "Less than 7% of the money is going for HIV prevention among MSM. To be strategic we need to increase investment for MSM programming especially younger MSM in cities" said Midnight.

Dr Ishwar Gilada, ASI

Dr Ishwar Gilada, President of AIDS Society of India, and a noted HIV physician who was among the first few medical professionals who responded to HIV care when first case was diagnosed in India, was moderating this panel discussion at AIDS 2014. "Unsafe sexual practices among transgender women were rare at that time when I did my study with Hijra community in 1983-1984. We could never have imagined then that Hijra community will come to International conferences. People used to laugh at them when transgender people used to come to JJ Hospital for care. I started a special clinic in OPD from 2pm-4pm in 1983 at JJ Hospital for transgender people. Back then we used to write male or female H (Hijra) as sex, but it took decades for government to finally recognize the third gender."

Dr BN Saxena

Dr Badri N Saxena, Chair of Microbicides Expert Group of Indian Council of Medical Research (ICMR) said (via web link) that there is hardly any choice under national HIV or STI prevention programmes except barrier method such as male condoms (female condoms are limited to very few targeted interventions or other social marketing initiatives). Few more options are available in private healthcare sector such as vaginal creams. Dr Saxena pointed out that there are 30 million episodes of STIs annually. Dr Saxena also advocated for a need-based phased introduction of Pre-Exposure Prophylaxis (PrEP) to provide another option to MSM people who might benefit from expanded range of HIV and non-HIV STI prevention options.

'Invisible' key population

Dr RR Gangakhedkar, NARI, ICMR (CNS Image library: December 2012)

Dr RR Gangakhedkar, Deputy Director, National AIDS Research Institute, ICMR said (via web link) that according to the mapping estimates there are 0.412 million MSM in India. Overall HIV prevalence rate among MSM is 4.4% and TGs is 8.8% (2011). There are targetted interventions (TIs) for both key populations in India offering STI services, linkage with HIV testing and care services, condom promotion, peer education, outreach, among others. There are over 201 MSM TIs that include over 37 community-based organizations-led TIs. Coverage as per the MSM population estimates is over 70%. Additionally, a program named "Pehchan" is also being implemented. 20 TIs are exclusively for transgender people.

Dr Gangakhedkar added: Though the overall coverage is high among MSM TIs, very little is known about the coverage in 'invisible' part of MSM population. With re-criminalization of same sex behaviour perhaps more MSM may opt to be 'invisible'.

Stigma lurks

(L-R) Dr I Gilada, Midnight P, Dr V Chakrapani, Dr Suwat C

Although situation has changed some shades for the better, but still stigma in healthcare settings rages high and often blocks access to existing services for MSM and transgender people even today.Dr Venkatesh Chakrapani, Director, Centre for Sexuality, Health Research and Policy, said: "Knowledge about HIV and STIs is perhaps not that big a challenge because despite knowledge, condom use among MSM and transgender people is low. For example they may not like to use condoms with their regular partners. If I need treatment for anal STIs I need to disclose to the doctor that I am MSM. Likewise talking about partner notification and simultaneous treatment of STIs in both partners becomes a huge challenge if stigma lurks in healthcare settings in India. Another issue is that condoms are free but lubes are not. Including lubes will help with dealing with issues such as condom breakage and augmenting HIV prevention among MSM and transgender."

Dr Chakrapani remarked that re-criminalization of consensual same-sex activity in India is having negative impact on health services for MSM and transgender people. "We spoke with few doctors this year and some of them were not clear if they should report to police if any MSM and transgender person comes to seek treatment for anal STIs. Some doctors were also not clear on whether they are abetting a crime by managing anal STIs among MSM and transgender people. No wonder MSM and transgender people are often reluctant to seek care in government hospital."

Unique needs and contexts of transgender people

Simran Shaikh, India HIV/AIDS Alliance

Simran Shaikh, a leading transgender activist with India HIV/AIDS Alliance, lamented that despite advocacy transgender related issues still get overshadowed by MSM related issues. She called for more space for addressing transgender issues as they are unique and need special attention. She said that there are exclusive transgender and Hijra interventions taking place now in India but we need to accelerate the scale up. Simran said that national HIV rates among transgender and Hijras are as high as 8.4% in India (general population HIV rate is about 0.27%). She mentioned specific situations that escalate this risk for transgender and Hijra community such as lack of opportunities for education, employment, or other social support systems.

Simran too echoed concerns that current STI and HIV prevention options are not working well enough and uptake remains low. Condom negotiation is very difficult for a transgender person to do with a client or regular partner, said Simran. She identified high consumption of alcohol and substance abuse among transgender people in India as another key challenge that ups their vulnerability to HIV and abuse.

Rectal Microbicides provide hope

(L-R) Midnight P, Dr V Chakrapani, Dr Suwat Chariyalertsa, RIHES

Dr Suwat Chariyalertsak, Director, Research Institute for Health Sciences (RIHES), Chiang Mai University, Thailand, who is a key researcher at this site for a rectal microbicide phase II study (MTN017), explained that we need to expand the range of HIV prevention options for those practicing anal sex.

Rectal microbicides– in the form of gels or lubricants – are products that are currently under research and are being developed and tested to reduce a person's risk of HIV or other sexually transmitted infections from anal sex. The risk of becoming infected with HIV during unprotected anal sex is 10 to 20 times greater than unprotected vaginal sex because as the rectal lining is only one-cell thick, the virus can more easily reach the immune cells and infect them.

Dr Suwat shared that the first-ever phase-II extended-safety study (formally called MTN017) of a rectal microbicide in the Asia-Pacific region has begun in Chiang Mai, Thailand since February 2014. In total, there are 8 study sites including Chiang Mai, such as: CDC Bangkok (where study will commence very soon), South Africa, Peru and in US. The objective of this rectal microbicide study is to study the safety and acceptability of a rectal microbicide gel for now. This study will perhaps also give information on issues such as adherence of study participants to the study product. Depending upon the outcome of this study (if study product is found safe and acceptable) efficacy studies will be conducted later. In this study, every MSM and female transgender study participant will have the same duration of exposure (eight weeks) to three different regimens (with a one week gap between each regimen): oral Truvada/PrEP daily for eight weeks, rectal gel (reduced glycerin and tenofovir gel) daily for eight weeks, and sex dependent rectal gel for eight weeks (applied anytime during the window period of 12 hours before and 12 hours after having anal sex).

Brian Kanyemba

Brian Kanyemba, Desmond Tutu HIV Centre, Cape Town, South Africa said that phase II study of rectal microbicide (MTN017) has also started at their site which is the only site in Africa. 7 out of 24 study participants have been enrolled so far.

Condoms... and lubes!
Jim Pickett, Chair of International Rectal Microbicide Advocates (IRMA) said in a press conference at AIDS 2014 (via web-link): Project ARM (Africa for Rectal Microbicides) was started by the IRMA few years ago to make sure that as the HIV prevention field moves ahead for research and development of rectal microbicides, these products [when eventually made available] are safe, accessible, and affordable to the people who need them [in African context]. There was a realization that we need to do some specific work in Africa in context that there are many countries where anal sex is illegal, people can be prosecuted and there is lot of [anal sex related] stigma and discrimination too."

Jim Pickett (CNS image library: July'12)

"Project ARM was born out of the growing need to create a research and advocacy agenda for rectal microbicides in Africa. Project ARM shows us what are the priorities in terms of research, advocacy and community mobilization around rectal microbicides in African context. One of the priorities that came out of Project ARM discussions was lube access. The reason was that people who practice anal sex cannot access lubricants."

"We have to recognize that it is not just MSM and transgender people who have anal sex but also men and women in heterosexual relationships. If that route of HIV transmission is not looked at then HIV rates are bound to rise in those practicing anal sex."

Jim briefed about "Global Lube Access Mobilization - GLAM". He said "Having safer lubes will not be enough unless policies and programmes start addressing access to lubes. This is how GLAM came into being. If we provide condoms to people and not provide lubes then it is a big problem because then people use whatever they can find and at times they use lubricants or products that are not condom compatible. Lack of condom compatible lubricants in Africa was acute. With no lubes people often resort to body lotions, cooking oil, pre-cum, creams or other things that are not necessarily condom compatible."

IRMA grants announced
Jim Pickett announced in this press conference that few grants have been awarded to some projects to advocate for national and local-level access to safe, affordable, condom-compatible lubricant in Africa to improve the impact of HIV prevention services. These projects are based in African countries such as Cameroon, Ghana, Kenya, Nigeria, Tanzania among others. This is the second year for IRMA to support projects in Africa. This year the grants are supported by amfAR, AVAC - Global Advocacy for HIV Prevention, COC Netherlands, and IRMA.

PrEP and WHO Guidance for key populations

(L-R) Deirdre Grant, Dr Ishwar Gilada, Midnight Poonkasetwattana

Deirdre Grant from AVAC – Global Advocacy for HIV Prevention said that "WHO Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations" which were released at AIDS 2014, are first set of guidelines for key affected populations that not only addressed the common areas which affected them all, but also addressed population specific ones. Deirdre informed that these guidelines were for five key population groups which were: MSM, injecting drug users, sex workers, transgender people and people in prisons.

PrEP is recommended as an additional HIV prevention choice within comprehensive HIV prevention package for MSM in these guidelines. On use of PrEP by transgender people, Deirdre said that there needs to be more evidence before strong recommendation can be made for its use among this key population. Deirdre called for heightened advocacy around PrEP and noted that WHO guidance helps with agencies and funders but does not directly help people who want to access services. Lots of other issues such as barriers, investment needs, dearth of smart programming, lack of implementation science, etc must be addressed alongside rolling out the guidance.

Dr Seema Sahay,NARI,ICMR

Dr Seema Sahay, Deputy Director, National AIDS Research Institute (NARI), Indian Council of Medical Research (ICMR), who is a noted social scientist said: "We are focussing on how to reach ‘hidden’ MSM especially adolescent MSM as this population is also surfacing right now. This is one problem we will like to have some advocacy and challenge we face. We conducted a small qualitative study and realized that knowledge about PrEP is very low. 2/39 MSM had heard of that. There should be some education programme and advocacy for PrEP as message about PrEP has not reached majority of MSM."

Vijay Nair, who demonstrated leadership years ago in India to organize HIV positive MSM as a network called NIPASHA+. Currently he is involved with India HIV/AIDS Alliance. Vijay expressed concerns if new HIV prevention technologies will ever reach those MSM who are in need.

VIjay Nair

Discussions about these new HIV prevention technologies are often limited to global conferences or meetings with little ground work taking place in our countries. He expressed concern why it has taken over two decades to do female condom programming after US FDA approved it in 1993? PrEP was approved by US FDA in July 2012 but still there is no clear sense how PrEP will reach MSM in need. He agreed with Dr Seema Sahay's observation that there are 'hidden' MSM in India who are not part of (or perhaps do not want to be part of) targetted interventions for MSM, and PrEP could be an option for them.

source

Novel microbicide gel for vagina and rectum shows potential for HIV prevention

Research to be presented at world's largest pharmaceutical sciences meeting

Arlington, Va. — Researchers developed a first-of-its-kind microbicide gel formulation that shows promise for safe vaginal and rectal administration to prevent the sexual transmission of human immunodeficiency virus (HIV). This research is being presented at the 2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition, the world's largest pharmaceutical sciences meeting, in San Antonio, Nov. 10-14.

There are 35.3 million people living with HIV worldwide, according to the World Health Organization, and the virus is spread most often through both vaginal and anal intercourse.

Anthony Ham, Ph.D., and the microbicide research team at ImQuest BioSciences, along with colleagues from Duke University, Magee-Womens Hospital, and University of Pittsburgh, developed the DuoGel as a task of their Integrated Preclinical and Clinical Program for Topical Microbicides grant from the National Institutes of Health. The primary goal was to create a safe and effective gel for administration of antiviral products to both the vagina and rectum, whereas current gels are only recommended for vaginal application. This DuoGel will deliver ImQuest's antiretroviral compound IQP-0528.

Since the environments of the vagina and rectum are dissimilar and require different conditions for safe and effective drug delivery, ex vivo toxicity, permeability, and efficacy tests were performed in both ectocervical and colorectal tissues. The DuoGel containing IQP-0528 was applied to the tissues, which were then exposed to HIV-1. The gel sufficiently delivered the drug in both in vitro and ex vivo vaginal and rectal environments to prevent HIV-1 infection of these tissues.

"It is recognized that both vaginal and rectal intercourse occur during the same sexual act, so a single product that is safe for both compartments makes sense in terms of convenience, which is likely to result in higher compliance." said Ham. "In addition, these DuoGels will be much safer products for HIV prevention in males practicing receptive anal intercourse."

Currently, user compliance and acceptability are being evaluated with a placebo DuoGel. The research team is preparing the current gel for animal studies and Investigational New Drug submission, and they hope to begin phase 1 of clinical trials in early 2015. The next stage in the research is to enhance the formulation by creating a multidrug DuoGel that also contains tenofovir, a second antiretroviral drug.

###

The 2013 AAPS Annual Meeting and Exposition aims to improve global health through advances in pharmaceutical sciences, and there will be 480 exhibits and an estimated 8,000 attendees. The meeting features nearly 105 programming sessions, including more than 50 symposia and roundtables. Download the AAPS smartphone application for additional information.

Editor's Note: All press must provide press credentials to attend this meeting and register on-site in the press room #213. To schedule an interview with Dr. Ham or for any other press inquiry, please contact Hillarie Turner or Dana Korsen at aaps@ecius.net or 202-296-2002. For the most up-to-date program information, please click here.

About AAPS:

The American Association of Pharmaceutical Scientists is a professional, scientific association of approximately 11,000 members employed in academia, industry, government and other research institutes worldwide. Founded in 1986, AAPS provides a dynamic international forum for the exchange of knowledge among scientists to serve the public and enhance their contributions to health. AAPS offers timely scientific programs, on-going education, information resources, opportunities for networking, and professional development. For more information, please visithttp://www.aaps.org. Follow us on Twitter @AAPSComms; official Twitter hashtag for the meeting is: #AAPS2013

Contact: Dana Korsen
aaps@ecius.net
301-744-9636
American Association of Pharmaceutical Scientists 

Vaginal Microbicide Shown Effective in Laboratory Study

NEW YORK (5 January 2011)--

Population Council director of biomedical HIV research Melissa Robbiani and her team demonstrated that a vaginal gel called PC-1005 completely protected monkeys from infection with the strain of the virus that causes AIDS in monkeys for up to 24 hours, according to a study published today in PLoS ONE.

PC-1005 contains low doses of MIV-150 and zinc acetate. MIV-150 is a potent non-nucleoside HIV reverse transcriptase inhibitor, or NNRTI, that prevents HIV infection of cells. Zinc acetate is a naturally occurring salt that has antiviral properties. The combination gel was applied once daily during a two-week trial period.

This research is part of the Population Council's efforts to develop and introduce safe, effective microbicides for vaginal and/or rectal use to prevent the transmission of HIV and other sexually transmitted infections. "Based on these excellent results, the MIV-150/zinc acetate gel is the Population Council's lead microbicide candidate," said Robbiani.

The small amount of pharmaceutical ingredients in PC-1005-0.002 percent MIV-150 and 0.3 percent zinc acetate-could translate into a low-cost, safe microbicide. In addition, a product that is used once daily may provide women with a convenient, easy-to-use HIV prevention option.

Robbiani's team also tested a zinc acetate-only version of the gel. While not as effective as the combination product, this formula offers significant protection against simian immunodeficiency virus, and unpublished research indicates that it also may be effective against genital herpes.

Some HIV prevention products under development contain HIV treatment drugs, and there is concern that these candidates could lead to a treatment-resistant strain of HIV. However, MIV-150 and zinc acetate are not used to treat HIV, so there may be reduced risk that the two gels from the Population Council would contribute to the emergence of a drug-resistant form of HIV. Both versions of the microbicide gel have a seaweed-derived carrageenan base, which has been shown to be acceptable to women and safe for long-term vaginal use.

Based on the promising results published in PLoS ONE, as well as in vitro data on safety and efficacy, the Population Council's human testing of both the MIV-150/zinc acetate gel and the zinc acetate alone gel could begin in early 2012. (more)

Kenney, J., M. Aravantinou, R. Singer, M. Hsu, A. Rodriguez, L. Kizima, C.J. Abraham, R. Menon, S. Seidor, A. Chudolij, A. Gettie, J. Blanchard, J.D. Lifson, M. Piatak Jr., J.A. Fernandez-Romero, T.M. Zydowsky, and M. Robbiani. 2011. "An antiretroviral/zinc combination gel provides 24 hours of complete protection against vaginal SHIV infection in macaques," PLoS ONE 6(1): E15835.

Outside funding for this research was provided by the National Institutes of Health, US Agency for International Development, Swedish Ministry of Foreign Affairs, and Swedish International Development Cooperation Agency.

About the Population Council

The Population Council is an international, nonprofit, nongovernmental research organization that seeks to improve the well-being and reproductive health of current and future generations around the world and to help achieve a humane, equitable, and sustainable balance between people and resources. The Council conducts biomedical, social science, and public health research and helps build research capacities in developing countries. Established in 1952, the Council is governed by an international board of trustees. Its New York headquarters supports a global network of regional and country offices

###

Media contact

Diane Rubino: drubino@popcouncil.org; +1 212 339 0617

The Global Forum on MSM & HIV Stands with Global HIV Advocates in Congratulating CAPRISA on Prevention Breakthrough

Study gives hope for new and effective prevention tools for women, men who have sex with men and other vulnerable populations

Vienna, Austria (July, 20, 2010) - The Global Forum on MSM & HIV (MSMGF) stands with HIV advocates around the world in congratulating scientists at the Center for the AIDS Programme of Research in South Africa (CAPRISA) on their new groundbreaking CAPRISA 004 trial results. CAPRISA 004 is an efficacy and safety trial that tested a1% tenofovir gel to prevent HIV transmission. Major findings included a 39 percent lower infection rate in those who used the gel compared to those who did not. Conducted in HIV-negative South African women, this was the first-ever trial to evaluate the efficacy of an antiretroviral-based microbicide; it is great cause for optimism regarding biomedical prevention approaches.

ARV-based HIV prevention entails, among other approaches, the use of microbicides as vaginal or rectal gels to reduce the chances of HIV transmission during sexual intercourse. We celebrate CAPRISA 004’s positive results as an important development for women’s advocates, who have highlighted the urgency of developing products that give women increased control over their own sexual health. The study is significant for the health of men who have sex with men (MSM) as well, with a growing global movement advocating microbicides research for rectal use.

It is important to note that CAPRISA 004 is a proof-of-concept study and that no microbicide, ARV-based or not, has yet been proven to effectively halt HIV transmission. The results and implications of the CAPRISA 004 trial must be confirmed through further research. In addition to efficacy trials, studies must be conducted to assess feasibility for potential roll-out and scale-up among different regional contexts and populations, including MSM.

Microbicides have the potential to become a formidable weapon in the fight against HIV among vulnerable populations. The CAPRISA 004 study focused solely on vaginal microbicides. More rectal microbicide research is needed in order to better understand their potential health benefits for MSM. Additionally, the complex and diverse challenges that MSM face around the world in regard to access, stigma, and criminalization have shown us that no one prevention technology can be a silver bullet.

Microbicides must therefore be understood as but one evolving part of an integrated prevention spectrum that employs a comprehensive range of already available, evidence-based approaches, from condoms and lubricants through structural interventions.

In order to ensure that such emerging HIV prevention technologies meet their full potential for reducing new infections, new science must be paired with strong advocacy. Each global region is different and requires a culturally competent and nuanced approach, but the need for action remains universal. We applaud these scientists for their efforts to enhance the tools at our disposal; it is now everyone’s responsibility to ensure that these tools are developed and released into a world that can use them.

While more exciting progress on ARV-based interventions is anticipated in the future, we must continue to stress the importance of a comprehensive and balanced approach in the fight against HIV – one that emphasizes targeted rights-based primary prevention strategies for communities that are especially vulnerable to HIV infection combined with treatment and support services for all people living with HIV.

IPM 015 Phase I/II expanded Safety Trial in Africa of an Antiretroviral-Containing Vaginal Ring Designed to Prevent HIV

Study in Southern and East Africa evaluates safety and acceptability of combining proven, long-acting women's health technology with antiretroviral drugs to prevent HIV


WASHINGTON, June 8 /PRNewswire/ --
The nonprofit International Partnership for Microbicides (IPM) today announced the initiation of the first trial among women in Africa testing a vaginal ring containing an antiretroviral drug (ARV) that could one day be used to prevent HIV transmission during sex. The clinical trial, known as IPM 015, tests the safety and acceptability of an innovative approach that adapts a successful technology from the reproductive health field to give women around the world a tool to protect themselves from HIV infection.
"Vaginal rings, commonly used in Europe and the U.S. for hormone delivery, could be well-suited to deliver HIV prevention drugs for women in developing countries," said Dr. Zeda Rosenberg, IPM's Chief Executive Officer. "This study will provide key information on the safety and acceptability of this technology for HIV prevention. It is an important step forward in our efforts to give women options they can use to safeguard their health."

Since 2001, women in developed countries have successfully used vaginal rings, such as the NuvaRing®, ESTRING® and Femring®, for birth control and hormonal therapy. These rings are appealing because they are self-administered, discreet and provide protection for a month or more. The vaginal ring being tested in IPM 015 is an ARV-based microbicide -- a class of vaginal products currently being developed to prevent HIV infection in women. ARVs have revolutionized HIV treatment and have already been proven to reduce mother-to-child transmission of HIV. They are now being tested for their ability to prevent HIV infection.

The vaginal ring used in IPM 015 is made of flexible silicone, is durable and would be easy to distribute -- making it well suited for use in developing countries. Each ring slowly releases 25 mg of the ARV drug dapivirine over the course of 28 days, potentially providing sustained protection against HIV. The ring is manufactured by IPM, which has a royalty-free license for dapivirine from Tibotec Therapeutics, a division of Johnson & Johnson.

"Biology and gender inequality continue to place women at greater risk of disease and death, particularly in developing countries," said Elizabeth Mataka, the UN Secretary-General's Special Envoy for AIDS in Africa. "All too often, women are not in a position to control their sexual health or protect themselves from HIV infection. By empowering women with new tools to protect their health, this ring technology could bring hope where there was none before."

IPM 015 is a Phase I/II expanded safety trial that will compare the dapivirine ring with a placebo ring containing no active drug among 280 volunteers across Africa. Women in South Africa have begun volunteering for the trial, and it is hoped that other African nations will start the same study shortly. The women volunteers will be randomly assigned to use either the dapivirine or the placebo ring, which will be replaced once monthly for a three-month period.

The vaginal ring containing dapivirine has already been shown to be safe as tested in four prior IPM clinical trials among women in Europe, with another trial ongoing. If IPM 015 further confirms the safety and acceptability of the product among women in Africa, a Phase III program to test the ability of dapivirine rings to prevent HIV infection is scheduled to begin in Africa in 2011, with results due in 2015.
“The roll-out of treatment in the past few years has saved millions of lives, but the AIDS epidemic continues to spread, with women particularly vulnerable,” said Michel Sidibe, the Executive Director of UNAIDS. “Preventing HIV transmission is essential if we are to protect the health and safety of future generations.

If successful, innovations, like microbicides, could have an extraordinary impact.”
Every day more than 3,000 women worldwide become infected with HIV. And HIV/AIDS is the leading cause of death for women aged 15-49 years in Africa. Despite this challenge, women lack a discreet method to prevent infection. Current prevention options may be impractical for women who lack the power to ensure that their male partners use condoms or remain faithful, and for those who are married, want to have children or are at risk of violence.

The initiation of IPM 015 was announced at the Women Deliver conference in Washington, D.C., the largest conference focused on maternal health in more than a decade.

"Women and girls must be given the tools to protect themselves from HIV infection," said Jill Sheffield, President of Women Deliver. "The contraceptive ring has been a formidable tool for women seeking more control over their reproductive health, and it is wonderful to see HIV researchers adapt this technology to tackle the single biggest killer of young women. The simple fact is that we will never be able to fully ensure the health of women and girls globally without halting the spread of HIV and AIDS."

About IPM: IPM is a nonprofit product development partnership established in 2002 to prevent HIV transmission by supporting the development and availability of safe and effective vaginal microbicides and other HIV prevention methods in developing countries where women are at greatest risk for infection. IPM has offices in the United States, South Africa and Belgium. Please visit http://www.ipmglobal.org/

SOURCE: International Partnership for Microbicides