News

CONRAD's TFV LNG Intravaginal Ring In the News

Dr. Meredith Clark Presents Animal Study Data at AAPS
November 22, 2013

HealthDay

Intravaginal Ring Offers Dual Protection for 90 Days

November 13, 2013

(HealthDay News) – An intravaginal ring containing drugs to prevent HIV transmission as well as pregnancy is able to deliver the drugs at effective levels for 90 days, according to a study presented at the annual meeting of the American Association of Pharmaceutical Scientists, held from Nov. 10–14 in San Antonio.

Patrick Kiser, PhD, from the University of Utah in Salt Lake City, and colleagues designed an intravaginal ring using reservoir-type polyurethane segments. The segments were individually optimized to deliver a high flux of tenofovir (the only topical HIV transmission prophylactic effective in gel form) and a low flux of levonorgestrel (a contraceptive). The intravaginal ring was tested by in vitro release testing and three-month pharmacokinetics studies in rabbits and sheep.

The researchers found that levels of the two drugs were time-independent and tunable, and were optimized to a target of 10mg/day tenofovir and 10 or 20µg/day levonorgestrel. Local levels of tenofovir in the target tissue were similar or higher than the levels following application of a 1% tenofovir gel. The release of levonorgestrel was consistent with levels known to be efficacious in women.

"We developed a unique intravaginal ring technology that met our product objectives of delivering a high flux of a hydrophilic antiretroviral (tenofovir) with a low flux of a hydrophobic contraceptive (levonorgestrel) in a controlled, time-independent manner for 90 days," Kiser and colleagues conclude.

Several authors are employees of CONRAD, which is contributing to the development of the intravaginal ring.


San Antonio Express-News

Birth-control ring may block HIV

November 13, 2013

Researchers are developing a vaginal ring that can deliver a 90-day supply of both an anti-HIV drug and a contraceptive.

They presented the findings Tuesday at the 2013 American Association of Pharmaceutical Scientists' Annual Meeting and Exposition in San Antonio.

Organizers expect the gathering, which ends Thursday, to draw about 8,000 attendees.

Meredith Clark, manager of drug delivery at CONRAD, a Virginia-based nonprofit reproductive health and HIV prevention organization, co-authored the study and called the device a “first of its kind,” though the drugs it uses are not new. It will soon move into clinical trials.

Clark, also an assistant professor at Eastern Virginia Medical School, hopes the ring might someday be an inexpensive option for women in developing countries, such as sub-Saharan Africa.

“Condoms are a very effective tool at preventing the transmission of HIV and other sexually transmitted diseases but, unfortunately, not all women have the ability to negotiate condom use,” she said. “The idea is to provide these women products they could ... potentially use discreetly and give them the power to protect themselves.”

She said her colleagues presented research last year on a vaginal ring that releases the drug tenofovir, which, in a gel form, has been shown to reduce the sexual transmission of human immunodeficiency virus, or HIV, in women.

But the new ring is the first to release both tenofovir and levonorgestrel, a contraceptive, over a 90-day period. She said there's potential that the ring could prevent the transmission of the herpes simplex virus as well.

Clark's research, funded through a cooperative agreement with the U.S. Agency for International Development, is one of several scientific fronts in the effort to combat the spread of HIV. Researchers at the Texas Biomedical Research Institute in San Antonio, for example, have applied for a patent for a vaccine to help prevent contracting HIV.

In 2012, about 35.3 million people were living with HIV globally, 69 percent of whom lived in sub-Saharan Africa, according to the World Health Organization.

In Bexar County, 4,316 people were living with an HIV diagnosis in 2010, according to the San Antonio Metropolitan Health District.

Vanessa Gonzales, director of prevention at the San Antonio AIDS Foundation, said the benefits of the ring will boil down to how effective it is at preventing the spread of HIV and whether it detracts from condom use.

She worries that using a ring while having unprotected sex could leave a woman exposed to contracting other sexually transmitted diseases.

“While this (innovation) is good, I just hope it won't take away from the message that people need to use condoms,” Gonzales said.

The flexible ring is 5.5 centimeters across and 5.5 millimeters thick, Clark said. It uses different grades of polyurethane tailored to deliver the two drugs, since tenofovir must be delivered at a rate that's about 500 to 1,000 times higher than levonorgestrel, she said.

Thus far, the ring or segments of it have only been tested on sheep and rabbits. It's designed to be pinched into a figure eight so a woman can insert it into her vagina and then replace it after three months, Clark said.

The U.S. Food and Drug Administration has already approved a chemically modified version of tenofovir for oral treatment, Clark said. It remains to be seen how well the ring will protect humans against HIV. Researchers will begin testing it on women early next year, and the device is likely years away from reaching the market, she said.

HealthLine.com

First Intravaginal Ring to Protect Against Pregnancy, HIV, and Herpes

November 12, 2013

The first device of its kind simultaneously prevents HIV, HSV-2, and pregnancy for 90 days.

Collaborative research from the University of Utah and reproductive health research organization CONRAD is working toward the goal of liberating contraceptive access with the first multipurpose pregnancy and disease prevention technology of its kind to be clinically tested.

The device, an intravaginal ring that simultaneously prevents pregnancy and reduces the risk of HIV and herpes simplex virus 2 (HSV-2) transmission, was presented this month at the 2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition in San Antonio, Texas.

By combining two technologies into one device, the ring could make huge gains in protecting the health of women and their partners, especially in regions with high rates of unintended pregnancies and HIV transmission.

How Does It Work? 

Intravaginal and intrauterine devices are not new, but the function of this particular product is unlike most currently on the market. The contraceptive levonorgestrel, when combined with the topical microbicide tenofovir, can prevent both unintended pregnancy and the transmission of HIV and HSV-2 for up to 90 days. The ring is designed to dispense a specific, controlled amount of levonorgestrel and tenofovir over time.

“By having a ring that can remain in the body for up to 90 days, our hope is that this ring will offer a solution to increase adherence, and therefore provide greater protection against HIV while also preventing pregnancy,” said Dr. David Friend, product development director at CONRAD, in a press release.

Researchers performed tests in rabbits and sheep and compared the results to the effectiveness of tenofovir gel alone, which has been proven successful in preventing HIV infection in women. When using the ring, researchers found that levels of tenofovir in the target tissue were similar to or higher than those from gel application alone. The contraceptive levels were also on target with what is regarded as effective for women.

Why Do Women Need Another Form of Contraception? 

Many forms of contraception, including condoms, tend to be controlled by men in developing countries, says Dr. Meredith Clark, manager of drug delivery at CONRAD. But a device like the intravaginal ring could signal a change in how people view contraception. “This is a product that is used and controlled by the woman,” Clark says.

Multipurpose prevention technology is rare among mainstream birth control options. While condoms are very good at protecting against both pregnancy and HIV, the development of a device like the intravaginal ring demonstrates the potential for many more kinds of contraception, especially those that give women more control over their sex lives.

The initial experiments show promise, but the success of the ring ultimately depends on whether people will feel comfortable using it.

“The introduction and acceptance of the ring needs to be explored,” Clark says. She predicts a learning curve but is optimistic about the ring’s possibilities and making a dent in the HIV/AIDS pandemic in regions like sub-Saharan Africa.

“We really hope this concept opens doors to getting [contraception] into women’s hands,” she says. 

Phase 1 clinical trials in humans will begin in 2014, when both the multipurpose ring and a tenofovir-only ring will be tested.


Refinery29.com

New Anti-HIV & Birth Control Ring Begins Trials Soon

November 12, 2013 

A brand new intravaginal ring (IVR) has shown exciting promise in both protecting against unwanted pregnancy and HIV. The ring has been engineered to release tenofovir and levonorgestrel — the first time both these drugs and the unique IVR delivery have been used in tandem. (Tenofovir, when in gel form, is the only compound that has been shown to protect against the sexual transmission of HIV. Levonogestrel is a hormone already used in contraceptives.)

But, while the use of tenofovir has been shown to substantially reduce the transmission of HIV when used before exposure — it is by no means 100% effective. And, since researchers are saying the tenofovir-release ring has similar success rate to that of the gel, a condom would definitely still be necessary to more completely protect against the disease. 

That being said, there are millions of people who are HIV-positive in the world, and there are millions more unintended pregnancies. Often, these occur in some of the poorest countries in the world — places where medical care is sparse or unaffordable. A simple, affordable option that can help to protect women for disease and pregnancy could be a HUGE deal, both here and abroad.

Phase I clinical trials are set to being early in 2014. (Eureka Alert)

POSITIVELY AWARE

First Dual-Protection Intravaginal Ring Shows Promise in HIV, Pregnancy Prevention

A new intravaginal ring (IVR) has been developed for the sustained 90-day co-delivery of tenofovir and levonorgestrel, an anti-HIV drug and a contraceptive. Tenofovir (brand name Viread) is the only HIV drug shown to be effective at reducing the sexual transmission of HIV when formulated in a gel. This research was presented at the 2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition, the world's largest pharmaceutical sciences meeting, in San Antonio, November 10-14.

While there are 35.3 million people living with HIV around the world, approximately 87 million unintended pregnancies occur each year, according to the World Health Organization. Meredith Clark, PhD, and David Friend, PhD, from CONRAD, a reproductive health research organization, in collaboration with the University of Utah, created this IVR using a multi-purpose prevention technology (MPT) to concurrently protect women from the sexual transmission of HIV and unintended pregnancy.

They designed the ring using reservoir-type polyurethane segments that were individually optimized to deliver each drug at the desired dosage—a high flux of tenofovir and low flux of levonorgestrel. The researchers performed in-vitro release testing, and 3-month pharmacokinetic (PK) studies in rabbits and sheep were done comparing the ring against tenofovir gel.

The PK studies found that local levels of tenofovir in the target tissue delivered from the IVR are similar or higher than the levels following gel application. In addition, release of the contraceptive agent was consistent with previous levels tested to be efficacious in women.

“We saw the urgent need to make this dual-protection intravaginal ring because a majority of the world's unintended pregnancies occur within resource-poor regions where the HIV/AIDS pandemic is most prevalent, such as sub-Saharan Africa,” said Clark. “MPTs are a relatively new reproductive health technology that we expect will have a good deal of support from potential users, donors, and public health organizations, particularly in the developing world. We anticipate a lot of excitement for this product, as it is the first dual-protection ring to be evaluated clinically.”

A team of investigators led by Patrick Kiser, PhD, now at Northwestern University, in partnership with CONRAD, presented research at the 2012 AAPS Annual Meeting on an intravaginal ring to deliver solely tenofovir (read PA’sinterview with Dr. Kiser in the upcoming January+February issue).

CONRAD's Product Development group and collaborators are continuing stability studies now and anticipate beginning with phase 1 clinical trials in women in early 2014, testing the combination anti-HIV/contraceptive IVR versus the anti-HIV-only IVR.

HIVandHEPATITIS.COM

AAPS Showcases Vaginal Ring with Tenofovir + Contraceptive, Gel Suitable for Vaginal and Rectal Use

November 15, 2013

Written by Liz Highleyman

A new intravaginal ring delivers both tenofovir for HIV prevention and levonorgestrel for contraception for 3 months, researchers reported at the American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition taking place this week in San Antonio. Other studies looked at a novel gel for both vaginal and rectal use containing the antiretroviral IQP-0528, and a bio-adhesive vaginal gel combining tenofovir and the anti-herpes drug acyclovir.

 The field of biomedical HIV prevention has seen major advances in recent years. Pre-exposure prophylaxis (PrEP) using oral tenofovir or Truvada (tenofovir/emtricitabine) has been shown to dramatically reduce the risk of HIV infection in various populations, but it only works with good adherence. Researchers are therefore exploring other delivery methods that might be more convenient and encourage better adherence than daily pills.

The CAPRISA 004 trial showed that a 1% tenofovir microbicide gel applied before and after sex decreased HIV acquisition by about 40% overall. A similar gel is also being tested for rectal use during anal sex. Tenofovir gel also offers protection against herpes simplex virus type 2 (HSV-2), which causes genital herpes.

Tenofovir/Levonorgestrel Ring

Another method uses a hollow intravaginal ring that releases tenofovir or other compounds over time, allowing them to be left in place and not requiring insertion right before having sex. This type of ring has been shown to protect macaque monkeys from vaginal exposure to an HIV-like virus.

Multipurpose prevention technologies (MPTs) -- for example, combining protection against HIV and other sexually transmitted infections, or HIV protection and contraception -- could further improve convenience and encourage consistent use.

Patrick Kiser from Northwestern University, Meredith Clark from the reproductive health research organization CONRAD, and colleagues evaluated an intravaginal ring designed for sustained co-delivery of tenofovir and the hormonal contraceptive levonorgestrel (a synthetic progesterone) for 90 days.

Because these agents have different biochemical properties and release rates, they can be difficult to administer together. In particular, tenofovir is hydrophilic and attracts water, while levonorgestrel is hydrophobic and repels water (this article from MIT explains the difference).

The researchers developed a segmented polyurethane ring with separate reservoirs that can deliver both drugs simultaneously. They used tubes of different lengths to change the amount of drugs released. After optimizing segments for each drug, they tested the combination rings in rabbits and sheep.

By altering release rates, they were able to achieve target levels of 10 mg/d for tenofovir and 10 or 20 mcg/d for levonorgestrel. In sheep, pharmacokinetic studies showed tenofovir levels in vaginal tissue and fluid similar to those obtained with 1% tenofovir gel in human clinical trials.

"We saw the urgent need to make this dual-protection intravaginal ring because a majority of the world's unintended pregnancies occur within resource-poor regions where the HIV/AIDS pandemic is most prevalent, such as sub-Saharan Africa," Clark explained in an AAPS press release. "MPTs are a relatively new reproductive health technology that we expect will have a good deal of support from potential users, donors, and public health organizations, particularly in the developing world."

"Products only work when they are used," added CONRAD product development director David Friend in another press release. "By having a ring that can remain in the body for up to 90 days, our hope is that this ring will offer a solution to increase adherence, and therefore provide greater protection against HIV while also preventing pregnancy."

CONRAD and collaborators anticipate starting Phase 1 clinical trials in women in early 2014, comparing the combination tenofovir/levonorgestrel ring versus the tenofovir-only version.

As described in another presentation, Kiser and colleagues are also working on "osmotic pump" technology for releasing compounds into the vagina regardless of their chemical properties. They have tested this technology in a segmented intravaginal ring that releases the experimental HIV drug IQP-0528 (see below).

IQP-0528 DuoGel

Anthony Ham from ImQuest BioSciences and colleagues described the development of DuoGel, a microbicide gel for HIV prevention designed for both vaginal and rectal use.

The original 1% tenofovir gel used in CAPRISA 004 proved too irritating for rectal use, though a reformulated version containing less glycerin was more acceptable. The ImQuest team was motivated to develop a dual use product because many people have both vaginal and anal intercourse during the same sexual episode.

IQP-0528 is a pyrimidinedione compound that acts as both a non-nucleoside reverse transcriptase inhibitor (NNRTI) and HIV entry inhibitor. It has been tested invaginal gels and vaginal films, both alone and in combination with tenofovir.

The researchers developed IQP-0528 DuoGels using "generally regarded as safe" excipients (inactive carrier compounds) approved for both vaginal and rectal administration, including hydroxyethyl cellulose, glycerin, methyl/propyl paraben, and carbomer. Starting with a vaginal formulation, they altered the pH and osmolality to be more suitable for rectal use.

They tested the gels' biochemical properties, drug release, toxicity, and anti-HIV activity in laboratory cell cultures. Toxicity, permeability, and efficacy were also evaluated in cervical and rectal tissue explants.

The best DuoGel formulation "displayed no in vitro cellular or bacterial toxicity" at the highest concentration tested (1000 mcg/mL) and "displayed no loss in viability in both explant ectocervical and colorectal tissue," the researchers concluded.

"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," Ham explained in an AASP press release. "In addition, these DuoGels will be much safer products for HIV prevention in males practicing receptive anal intercourse."

Acceptability and adherence are now being evaluated using a placebo DuoGel without the active ingredient, according to the release. The researchers are preparing the current gel for animal studies and hope to begin Phase 1 human clinical trials in early 2015. In the next stage they plan to create a multidrug DuoGel that contains IQP-0528 plus tenofovir.

Tenofovir/Acyclovir Gel

Finally, researchers from SRI International reported on the development of a vaginal gel combining tenofovir and acyclovir, which is used to treat and prevent outbreaks of genital herpes.

The research team developed gels made with different combinations of 2 polymers, Pluronic F-127 and Noveon AA1, and evaluated their biochemical properties under conditions simulating vaginal sex.

Among the tested gels, only one dubbed SR-2P retained its structure when diluted with simulated vaginal fluid and semen and subject to "mild simulated coital stress." This formulation showed good adhesion to pig vaginal tissue and caused little or no irritation in a mouse model.

Because tenofovir is compatible with Noveon AA1 while acyclovir is compatible with Pluronic F-127, the researchers are working on a dual-syringe strategy that administers the 2 drug/polymer mixes from separate compartments.

"The results of this study demonstrated the potential application of SR-2P as a vaginal microbicide vehicle for delivery of acyclovir and tenofovir," they concluded.

11/15/13

References

P Kiser, M Clark, J Clark, et al. Development and Pharmacokinetics of a 90-Day Intravaginal Ring for the Sustained Co-Delivery of the Microbicide Tenofovir and Contraceptive Levonorgestrel. American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition. San Antonio. November 10-14, 2013. Abstract T2063.

R Teller, R Rastogi, P Mesquita, et al. Intravaginal Osmotic Pump for Sustained Release of an HIV Prevention Agent. Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition. San Antonio. November 10-14, 2013. Abstract T2077.

A Ham, W. Lustig, S Nugent, et al. Formulation Development of the DuoGel: A Dual Chamber Vaginal/Rectal Anti-HIV Microbicide Gel. American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition. San Antonio. November 10-14, 2013. Abstract R6132.

S Podaralla, M Liu, B Francavilla, et al. Formulation Development of Acyclovir/Tenofovir Loaded Two-Polymer (SR-2P) Bioadhesive Vaginal Gel. American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition. San Antonio. November 10-14, 2013. Abstract T2073.

Other Sources

American Association of Pharmaceutical Scientists. First Dual-Protection Intravaginal Ring Design Shows Promise in Long-term HIV & Pregnancy Prevention. Press release. November 12, 2013.

CONRAD. CONRAD Presents New Technology Combining Contraception, HIV and Herpes Simplex Virus-2 (HSV-2) Prevention. Press release. November 12, 2013.

American Association of Pharmaceutical Scientists. Novel Microbicide Gel for Vagina and Rectum Shows Potential for HIV Prevention. Press release. November 14, 2013.


G1.Globo.com

Novo anel intravaginal pretende evitar contagio por HIV e gravidez indesejada

November 12, 2013

Produto deve ter primeiros ensaios clínicos em mulheres no início de 2014.
35,3 milhões têm HIV e 87% das gestações não são planejadas, diz OMS.

Um novo anel intravaginal foi desenvolvido para agir contra o vírus da Aids e gravidez indesejada ao mesmo tempo. O produto, apresentado esta semana na reunião anual da Associação Americana de Cientistas Farmacêuticos, no Texas, deve começar a primeira fase de ensaios clínicos em mulheres no início de 2014. As pacientes serão divididas em dois grupos: um receberá esse anel de dupla proteção e o outro, apenas prevenção contra o HIV.

Segundo os cientistas, da organização de pesquisa em saúde reprodutiva Conrad e da Universidade de Utah, o anel de poliuretano foi desenvolvido para durar 90 dias, período no qual deve liberar alta dosagem da substância anti-HIV tenofovir e baixa dosagem do contraceptivo levonorgestrel, um tipo sintético de progesterona (hormônio feminino).

O tenofovir é o único composto que tem se mostrado eficaz para redução da transmissão sexual do HIV quando formulado em gel. E os níveis da substância liberados pelo anel intravaginal foram iguais ou até superiores aos da aplicação em gel, destacaram os pesquisadores Meredith Clark e David Friend, da Conrad.

A equipe responsável pelo trabalho realizou testes in vitro e comparou os resultados com estudos farmacocinéticos (o caminho que um medicamento percorre no organismo, desde a ingestão até a excreção) feitos durante três meses em coelhos e ovelhas.

 Para Meredith, a necessidade desse anel surgiu porque a maioria das gestações indesejadas no mundo ocorre em regiões pobres onde a pandemia de HIV é mais prevalente, como a África Subsaariana.

De acordo com a Organização Mundial da Saúde (OMS), atualmente existem 35,3 milhões de pessoas vivendo com o vírus da Aids em todo o mundo e cerca de 87% das gestações por ano não são planejadas pelos casais.

MedIndia.net

CONRAD Enables Recent Technology Which Combines Contraception, HIV and Herpes Simplex Virus-2 Prevention

CONRAD Head of drug delivery, Meredith Clark, PhD, today presented preclinical data on a new intravaginal ring that provides contraception as well as HIV-1 and HSV-2 prevention at the 2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition in San Antonio, Texas. This multipurpose prevention technology (MPT) can remain in the vagina for up to 90 days and releases the contraceptive levonorgestrel (LNG) and tenofovir (TFV), an antiretroviral that inhibits HIV and HSV replication in susceptible cells.

The CONRAD product development team, in collaboration with Dr. Patrick Kiser at Northwestern University, performed in vitro release testing and 3-month pharmacokinetic (PK) studies of the ring in rabbits and sheep, and compared drug levels to those seen with use of tenofovir gel. The PK studies found that levels of tenofovir in the target tissuehttp://images.intellitxt.com/ast/adTypes/icon1.png delivered from the ring are similar or higher than those obtained after TFV 1% gel application, a product that has proven to be effective in preventing HIV and HSV infections in women. In addition, release of the contraceptive agent was also consistent with previous levels tested to be efficacious in women. Stability studies will continue and lead to Phase I clinical trials in women in 2014, which will test the combination ring, as well as a tenofovir-only ring.

Tenofovir is the first microbicide proven to be efficacious in humans, with the CAPRISA 004 clinical trial showing that women using the gel before and after sex reduced their riskhttp://images.intellitxt.com/ast/adTypes/lb_icon1.png of HIV infection by 39-54%. CAPRISA 004 also showed the gel to be 51% effective in reducing the transmission of HSV-2, making this combination ring potentially triple protective.

"The TFV/LNG ring is the first device to be tested in women that will offer contraception as well as HIV and herpes prevention," said Dr. Clark. "And so far, tenofovir is the only microbicide that has been proven to be effective in reducing HIV infections when used topically. It's important to develop a variety of delivery mechanisms for tenofovir in order to serve different women's needs."

MEDICAL NEWS TODAY

New technology combining contraception, HIV and herpes simplex virus-2 prevention

Thursday 14 November 2013 - 12am PST

CONRAD Head of drug delivery, Meredith Clark, PhD, presented preclinical data on a new intravaginal ring that provides contraception as well as HIV-1 and HSV-2 prevention at the 2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition in San Antonio, Texas. This multipurpose prevention technology (MPT) can remain in the vagina for up to 90 days and releases the contraceptive levonorgestrel (LNG) and tenofovir (TFV), an antiretroviral that inhibits HIV and HSV replication in susceptible cells.

The CONRAD product development team, in collaboration with Dr. Patrick Kiser at Northwestern University, performed in vitro release testing and 3-month pharmacokinetic (PK) studies of the ring in rabbits and sheep, and compared drug levels to those seen with use of tenofovir gel. The PK studies found that levels of tenofovir in the target tissue delivered from the ring are similar or higher than those obtained after TFV 1% gel application, a product that has proven to be effective in preventing HIV and HSV infections in women. In addition, release of the contraceptive agent was also consistent with previous levels tested to be efficacious in women. Stability studies will continue and lead to Phase I clinical trials in women in 2014, which will test the combination ring, as well as a tenofovir-only ring.

Tenofovir is the first microbicide proven to be efficacious in humans, with the CAPRISA 004 clinical trial showing that women using the gel before and after sex reduced their risk of HIV infection by 39-54%. CAPRISA 004 also showed the gel to be 51% effective in reducing the transmission of HSV-2, making this combination ring potentially triple protective.

"The TFV/LNG ring is the first device to be tested in women that will offer contraception as well as HIV and herpes prevention," said Dr. Clark. "And so far, tenofovir is the only microbicide that has been proven to be effective in reducing HIV infections when used topically. It's important to develop a variety of delivery mechanisms for tenofovir in order to serve different women's needs."

 CONRAD's product development director David Friend Ph.D added, "Products only work when they are used. By having a ring that can remain in the body for up to 90 days, our hope is that this ring will offer a solution to increase adherence, and therefore provide greater protection against HIV while also preventing pregnancy."

CONRAD's deputy director of clinical research, Marianne Callahan, will also present information on MPTs later this week at the International Conference on Family Planning in Addis Ababa, Ethiopia. The CONRAD sponsored panel, "Development of Multipurpose Prevention Technologies (MPTs): Pathway from Product Development to the End Users," will discuss how the development of MPTs are tied to the regulatory approval process, the importance of acceptability research within target populations, and the importance of taking a "systems approach" when considering feasibility of future introduction of a new technology.

In addition to the TFV/LNG intravaginal ring, CONRAD is testing the one-size-fits-most SILCS diaphragm with tenofovir gel. Used together, the diaphragm plus the gel can offer contraception plus the potential to reduce HIV and HSV-2 infections as an on-demand system providing immediate protection.

According to the World Health Organization, there are 35.3 million people living with HIV around the world and approximately 87 million unintended pregnancies occur each year. Ms. Callahan says, "An unintended pregnancy is more tangible than an invisible virus so MPTs may lead to increased product use by offering a crucial combination of protection that can have a major impact in developing countries."

New Intravaginal Ring To Provide HIV And Pregnancy Prevention: Dual Protection Device Is First Of Its Kind

By Lizette Borreli | Nov 12, 2013 01:39 PM EDT

Women who partake in vaginal sex may soon be able to protect themselves from both unintended pregnancies and the human immunodeficiency virus (HIV) with the use of a new kind of intravaginal ring.

Presented at the 2013 annual meeting of the American Association of Pharmaceutical Scientists (AAPS) — the world’s largest pharmaceutical sciences meeting — is the first dual-intravaginal ring (IVR). The IVR was developed for a 90-day co-delivery of tenofovir and levonorgestrel, an anti-HIV drug and a contraceptive.

The World Health Organization (WHO) says there are 35.3 million people living with HIV around the world. A person can become infected with the virus through the spread of body fluids. The disease affects specific cells of the immune system, known as CD4 cells or T cells. HIV compromises the body’s immune system and its ability to fight off infections and disease by destroying T cells, which can lead to acquired immune deficiency syndrome (AIDS) if left untreated, according to the Centers for Disease Control and Prevention. Although new cases are reported throughout all regions of the world, 95 percent of new infections occur in patients who live in low- and middle-income countries, particularly in sub-Saharan Africa.

Similarly, proportions of unintended pregnancies are substantially higher in South America and southern Africa, where there tends to be a lack of adequate resources for pregnancy prevention. Approximately 87 million unintended pregnancies occur each year, says WHO.

Researchers who developed the ring noticed that the majority of the world’s unplanned pregnancies occur in regions where there is a high prevalence of HIV rates. "We saw the urgent need to make this dual-protection intravaginal ring because a majority of the world's unintended pregnancies occur within resource-poor regions where the HIV/AIDS pandemic is most prevalent, such as sub-Saharan Africa,” Meredith Clark, Ph.D., of CONRAD, a reproductive health research organization, said in a statement

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In an effort to prevent long-term HIV and pregnancy, researchers Dr. Clark and David Friend, Ph.D., in collaboration with the University of Utah created the IVR using dual-protection, or multipurpose prevention technology (MPT), to simultaneously protect women from the sexual transmission of HIV and unplanned pregnancies during vaginal sex. MPTs are considered a relatively new reproductive health technology that will have support from medical experts and be particularly useful in developing countries.  

The device was designed by the team of researchers using reservoir-type polyurethane segments that were individually optimized to deliver each drug at the desired dosage, according to Medical Xpress. There will be a high flux of tenofovir and a low flux of levonorgestrel. Currently, tenofovir is the only topical prophylactic that is effective in a gel form at reducing the sexual transmission of HIV.

To test the effects of the ring, researchers performed in vitro release testing, and three-month pharmacokinetic (PK) studies in rabbits and sheep which were compared against the tenofovir gel. The PK studies revealed levels of tenofovir delivered from the IVR were similar or higher than levels seen with gel application of the anti-HIV drug. Also, the release of levonorgestrel from the IVF was found to be consistent.

At the 2012 AAPS Annual Meeting, A team of investigators led by Patrick Kiser, who is now at Northwestern University, presented research on an anti-HIV-only IVR that was developed in partnership with CONRAD. The 90-day IVR was developed for the delivery of tenofovir as a means to reduce the sexual transmission of HIV. The IVR tenofovir was tested in sheep and showed similar or higher levels of a short-lasting tenofovir vaginal gel that was proven to be clinically effective at reducing the risk of HIV infection in women.

CONRAD’S Product Development group and collaborators are currently performing studies but hope to begin phase 1 clinical trials in women early next year in order to compare the combination anti-HIV and contraceptive IVR to the anti-HIV IVR.

“We anticipate a lot of excitement for this product, as it is the first dual-protection ring to be evaluated clinically,” said Dr. Clark.

While there is no vaccine to protect against HIV and no cure for AIDS, there are still ways to preventative measures individuals can take to prevent the virus. The Mayo Clinicadvises those who engage in sexual intercourse to use a new condom every time during anal or vaginal sex.

For more information on HIV prevention, click here.


Asian News International

New intravaginal ring offers long-term HIV, pregnancy prevention

November 13, 2013

Washington: Researchers have developed a new intravaginal ring (IVR) developed for the sustained 90-day co-delivery of tenofovir and levonorgestrel, an anti-human immunodeficiency virus (HIV) drug and a contraceptive.

Tenofovir is the only topical prophylactic shown to be effective at reducing the sexual transmission of HIV when formulated in a gel. T

Meredith Clark, Ph.D., and David Friend, Ph.D., from CONRAD, a reproductive health research organization, in collaboration with the University of Utah, created this IVR using a dual-protection or multipurpose prevention technology (MPT) to concurrently protect women from the sexual transmission of HIV and unintended pregnancy.

They designed the ring using reservoir-type polyurethane segments that were individually optimized to deliver each drug at the desired dosage-a high flux of tenofovir and low flux of levonorgestrel.

The researchers performed in-vitro release testing, and 3-month pharmacokinetic (PK) studies in rabbits and sheep were done in comparison against the tenofovir gel.

The PK studies found that local levels of tenofovir in the target tissue delivered from the IVR are similar or higher than the levels following gel application. In addition, release of the contraceptive agent was consistent with previous levels tested to be efficacious in women.

CONRAD's Product Development group and collaborators are continuing stability studies now and anticipate beginning with phase 1 clinical trials in women in early 2014, testing the combination anti-HIV/contraceptive IVR versus the anti- HIV-only IVR.

l’Unita

Ricercatori Usa: contro l'Aids creato un anello intravaginale

November 13, 2013

L'annuncio al meeting dell'American Association of Pharmaceutical Scientists. L'anello proteggerebbe per tre mesi. Naturalmente servono prove e conferme.

Come d'obbligo in questi casi, serviranno conferme, prove, riscontri. A ogni modo rimbalza una notizia sulle agenzie e sul web: al meeting annuale dell'American Association of Pharmaceutical Scientists (Aaps) è stato presentato un anello intravaginale che – secondo i ricercatori - offrirebbe protezione a lungo termine dall'Hiv e dalle gravidanze indesiderate. L'anello è stato sviluppato per fornire costantemente per novanta giorni un mix di tenofovir, farmaco contro il virus dell'immunodeficienza umana, e levonorgestrel, contraccettivo. 

Il tenofovir è l'unico profilattico topico rivelatosi efficace nel ridurre la trasmissione sessuale dell'Aids in forma di gel. L'anello è stato realizzato da Meredith Clark e David Friend dell'organizzazione Conrad con la University of Utah ed è costituito da segmenti di poliuretano simili a serbatoi che sono singolarmente regolabili per fornire il dosaggio desiderato per i rispettivi farmaci.  

RHRealityCheck.org

New Device to Protect Against Pregnancy, Herpes, and HIV Is Possible

November 19, 2013

New technology debuted at the American Association of Pharmaceutical Scientists’ annual meeting last week will combine contraception and disease prevention into a vaginal ring. The small, flexible piece of plastic would be inserted high up in the vagina and could be left in place for 90 days. It would release both levonorgestrel, a hormonal contraceptive, and tenofovir, an antiretroviral that has been shown to inhibit the replication of HIV and herpes simplex virus-2 (HSV-2), one of the two strains of the virus that causes genital infections.

There is already a vaginal ring, called NuvaRing, on the market that can prevent pregnancy. Women insert the ring into their vagina and wear it continually for three weeks. They then remove it for one week, during which time they menstruate, and put a new ring in to start the cycle again. Similar to all hormonal methods of contraception, NuvaRing releases a combination of estrogen and progesterone to inhibit ovulation. NuvaRing does not provide any protection from sexually transmitted diseases.

Tenofovir is the first microbicide that has been proven to be effective in humans. In clinical trials, women who used a tenofovir gel before and after sex reduced their risk of HIV infection by 39 to 54 percent. The gel also reduced HSV-2 transmission by 51 percent.

The combination ring has thus far only been tested in animals but is moving into the human trial phase and has potential to be an important new tool for women. Women are more susceptible than men to both HIV and HSV-2 transmission during penile-vaginal sex, and researchers have been trying to develop products that women can control and use without needing their partner’s help or even consent. If it proves to be effective, this ring could be that method.

In addition to the combination ring, the drug company is also developing a tenofovir-only ring, and a one-size diaphragm (which will fit most women) that can be used with the tenofovir gel.

As it is just entering the trial phase, these products will not hit pharmacies for quite a while. In the meantime, it is important for both women and men to remember that currently only condoms can provide protection against both pregnancy and sexually transmitted diseases.

Red Orbit

New Technology Combines Contraception, HIV And Herpes Simplex Virus-2 Prevention

November 12, 2013

Multipurpose prevention technologies featured at AAPS Annual Meeting and International Conference on Family Planning

CONRAD Head of drug delivery, Meredith Clark, PhD, today presented preclinical data on a new intravaginal ring that provides contraception as well as HIV-1 and HSV-2 prevention at the 2013 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition in San Antonio, Texas. This multipurpose prevention technology (MPT) can remain in the vagina for up to 90 days and releases the contraceptive levonorgestrel (LNG) and tenofovir (TFV), an antiretroviral that inhibits HIV and HSV replication in susceptible cells.

The CONRAD product development team, in collaboration with Dr. Patrick Kiser at Northwestern University, performed in vitro release testing and 3-month pharmacokinetic (PK) studies of the ring in rabbits and sheep, and compared drug levels to those seen with use of tenofovir gel. The PK studies found that levels of tenofovir in the target tissue delivered from the ring are similar or higher than those obtained after TFV 1% gel application, a product that has proven to be effective in preventing HIV and HSV infections in women. In addition, release of the contraceptive agent was also consistent with previous levels tested to be efficacious in women. Stability studies will continue and lead to Phase I clinical trials in women in 2014, which will test the combination ring, as well as a tenofovir-only ring.

Tenofovir is the first microbicide proven to be efficacious in humans, with the CAPRISA 004 clinical trial showing that women using the gel before and after sex reduced their risk of HIV infection by 39-54%. CAPRISA 004 also showed the gel to be 51% effective in reducing the transmission of HSV-2, making this combination ring potentially triple protective.

“The TFV/LNG ring is the first device to be tested in women that will offer contraception as well as HIV and herpes prevention,” said Dr. Clark. “And so far, tenofovir is the only microbicide that has been proven to be effective in reducing HIV infections when used topically. It’s important to develop a variety of delivery mechanisms for tenofovir in order to serve different women’s needs.”

CONRAD’s product development director David Friend Ph.D added, “Products only work when they are used. By having a ring that can remain in the body for up to 90 days, our hope is that this ring will offer a solution to increase adherence, and therefore provide greater protection against HIV while also preventing pregnancy.”

CONRAD’s deputy director of clinical research, Marianne Callahan, will also present information on MPTs later this week at the International Conference on Family Planning in Addis Ababa, Ethiopia. The CONRAD sponsored panel, “Development of Multipurpose Prevention Technologies (MPTs): Pathway from Product Development to the End Users,” will discuss how the development of MPTs are tied to the regulatory approval process, the importance of acceptability research within target populations, and the importance of taking a “systems approach” when considering feasibility of future introduction of a new technology.

In addition to the TFV/LNG intravaginal ring, CONRAD is testing the one-size-fits-most SILCS diaphragm with tenofovir gel. Used together, the diaphragm plus the gel can offer contraception plus the potential to reduce HIV and HSV-2 infections as an on-demand system providing immediate protection.

According to the World Health Organization, there are 35.3 million people living with HIV around the world and approximately 87 million unintended pregnancies occur each year. Ms. Callahan says, “An unintended pregnancy is more tangible than an invisible virus so MPTs may lead to increased product use by offering a crucial combination of protection that can have a major impact in developing countries.”

1911 North Fort Myer Drive, Suite 900, Arlington, Virginia 22209   T: (703) 524-4744 | info@conrad.org