Featured Research

from universities, journals, and other organizations

Combination ARV vaginal ring to prevent HIV safe in trial but 1 ARV carries the weight, study suggests

Date:
March 4, 2014
Source:
Microbicide Trials Network
Summary:
An early phase clinical trial of a vaginal ring containing the antiretroviral (ARV) drugs dapivirine and maraviroc found the ring was safe in women who wore it for 28 days and evidence of dapivirine in cervical tissue and blood. In addition, laboratory tests of tissue samples showed that dapivirine was able to block HIV infection, though levels of maraviroc were not sufficient to have a similar effect, report researchers.

An early phase clinical trial of a vaginal ring containing the antiretroviral (ARV) drugs dapivirine and maraviroc found the ring was safe in women who wore it for 28 days and evidence of dapivirine in cervical tissue and blood. In addition, laboratory tests of tissue samples showed that dapivirine was able to block HIV infection, though levels of maraviroc were not sufficient to have a similar effect, reported researchers from the National Institutes of Health-funded Microbicide Trials Network (MTN) today at the 21st Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

The Phase I trial, known as MTN-013/IPM 026, was the first clinical study of a vaginal microbicide with two ARV drugs, and with the inclusion of maraviroc, the first involving an ARV belonging to a class of anti-HIV drugs called entry inhibitors. Microbicides are products applied inside the vagina or rectum to prevent the sexual transmission of HIV. Vaginal microbicides are being designed in many forms, including gels, films and rings that, once inserted into the vagina, release the active ingredient gradually over time.

"It's encouraging that both drugs were safe, and that most women didn't mind wearing the ring. However, we found maraviroc wasn't getting absorbed in tissue like dapivirine was and it didn't work as well as dapivirine in our laboratory studies looking at activity against HIV," explained Beatrice A. Chen, M.D., M.P.H., of the University of Pittsburgh School of Medicine and Magee-Womens Hospital of UPMC, who as protocol chair of MTN-013/IPM 026, presented the results on behalf of the study team.

Though the findings indicate that further work is needed on the development of the combination ring, they bode well for the dapivirine ring, which is currently being evaluated in two ongoing Phase III effectiveness trials in Africa: the ASPIRE trial led by MTN and The Ring Study led by the nonprofit International Partnership for Microbicides (IPM). IPM developed both the dapivirine ring and the combination dapivirine-maraviroc ring.

MTN-013/IPM 026 was designed to evaluate the safety, acceptability and drug absorption qualities of the dapivirine-maraviroc ring when worn by women for 28 days. It enrolled 48 HIV-negative women ages 18 to 40 at the University of Pittsburgh, The Fenway Institute in Boston, and the University of Alabama at Birmingham (UAB) and was conducted between September 2011 and September 2012. Women were randomly assigned to use either the combination dapivirine-maraviroc ring, a ring containing maraviroc alone, a ring containing dapivirine alone, or one with no active product. The rings are made of a silicone elastomer, each measuring 56mm (about 2 ผ inches) in diameter and 7.7mm thick (ผinch).

Of the few side effects experienced by women, most were considered mild in nature and not thought to be associated with use of the ring. Women also found the ring generally acceptable, although 17 percent of the women said they preferred not wearing the ring during menstruation. Of the 48 women in the trial, 45 of them kept the ring in place at all times throughout the 28 days.

"The vast majority of women said they had no discomfort wearing the ring, though some had some concerns about this. Most women said they forgot it was in place," said Lori Panther, M.D., M.P.H., of The Fenway Institute and Harvard University, who is the MTN-013/IPM 026 protocol co-chair. "The rings are quite similar to the vaginal ring currently approved for contraception."

Researchers collected samples of blood, vaginal fluid and cervical tissue at different time points during the four weeks that women wore the ring, as well as after it was removed, in order to assess how much of each drug was being absorbed. Dapivirine was detected in all three types of samples. Laboratory tests of cervical tissue biopsies from women using either the dapivirine-only ring or the combination dapivirine-maraviroc ring also showed that dapivirine protected the tissue against HIV infection. In addition, researchers noted a direct correlation between drug concentration levels and protection against HIV for both rings containing dapivirine in the lab tests.

Biopsies from women using the maraviroc-only ring did not show protection against HIV in the laboratory model and maraviroc was not detected in blood. Only 4 of 24 women using either the combination ring or the maraviroc-only ring had detectable levels of the drug in cervical tissue. Additional testing of blood is ongoing to determine whether the drug can be detected using more sensitive methods.

"As an entry inhibitor, maraviroc is a promising candidate for development as a microbicide for HIV prevention because it acts at a different step in the infectious process from other HIV prevention drugs" said Zeda F. Rosenberg, Sc.D., chief executive officer of IPM, a nonprofit organization developing HIV prevention tools and other sexual and reproductive health technologies for women. "IPM is conducting additional development work to increase the amount of maraviroc that gets into cervical tissue in order to best harness the drug's potential in the combination ring, and we are planning a second safety study for 2015."

IPM is developing maraviroc as a microbicide through a royalty-free licensing agreement with ViiV Healthcare. Maraviroc is approved for use in the treatment of HIV in combination with other ARVs and is marketed under the trade names Selzentry in the United States and Celsentri in Europe. Dapivirine, also known as TMC-120, is being developed as a monthly microbicide ring and in other formulations by IPM through a royalty-free licensing agreement with Janssen R&D Ireland.

The two drugs work against HIV in different ways. As an entry inhibitor, maraviroc is designed to block HIV from getting inside target cells, while dapivirine belongs to a class of ARVs called non-nucleoside reverse transcriptase inhibitors (NNRTIs) that prevent HIV from making copies of itself. Prior to MTN-013/IPM 026, clinical trials of ARV-based microbicides were only of products containing an NNRTI or nucleoside reverse transcriptase inhibitors (NRTIs). Tenofovir, for example, is an NRTI being tested in both vaginal and rectal microbicide gel formulations.

In addition to Drs. Chen and Panther, other authors of the MTN-013/IPM 026 study were Craig Hoesley, M.D. (UAB); Craig Hendrix, M.D. (Johns Hopkins University); Ariane van der Straten, Ph.D., M.P.H. (RTI International/Women's Global Health Imperative); Marla Husnik, M.S., (Statistical Center for HIV/AIDS Research and Prevention); Lydia Soto-Torres, M.D., M.P.H., (Division of AIDS, National Institute of Allergy and Infectious Diseases); Annalene Nel, M.D., Ph.D.(IPM); Sherri Johnson, M.P.H. (FHI 360); and Charlene Dezzutti, Ph.D. (University of Pittsburgh and Magee-Womens Research Institute).


Story Source:

The above story is based on materials provided by Microbicide Trials Network. Note: Materials may be edited for content and length.


Cite This Page:

Microbicide Trials Network. "Combination ARV vaginal ring to prevent HIV safe in trial but 1 ARV carries the weight, study suggests." ScienceDaily. ScienceDaily, 4 March 2014. <www.sciencedaily.com/releases/2014/03/140304125927.htm>.
Microbicide Trials Network. (2014, March 4). Combination ARV vaginal ring to prevent HIV safe in trial but 1 ARV carries the weight, study suggests. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2014/03/140304125927.htm
Microbicide Trials Network. "Combination ARV vaginal ring to prevent HIV safe in trial but 1 ARV carries the weight, study suggests." ScienceDaily. www.sciencedaily.com/releases/2014/03/140304125927.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) — Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) — Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) — Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
More People Diagnosed With TB In 2013, But There's Good News

More People Diagnosed With TB In 2013, But There's Good News

Newsy (Oct. 22, 2014) — The World Health Organizations says TB numbers rose in 2013, but it's partly due to better detection and more survivors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins