OF the more than 34 million people living with HIV worldwide, half are women and three quarters of the world’s HIV positive women live in the Sub-Saharan Africa.
Centre for Infectious Disease Research in Zambia (CIDRZ) Microbicide Trials Network (MTN) investigator Margaret Kasaro explains that the major driver for HIV among the women in this region, Zambia inclusive, is heterosexual intercourse.
In fact, studies have indicated that women are twice as likely as their male counterparts to contract HIV during sexual intercourse and this is mainly attributed to biological factors that more of them are susceptible.
“This is more so for younger women who are more vulnerable.
In Africa, young women are up to five times more likely to become infected with HIV than young men of their age group,” Dr Kasaro says.
On the other hand individual, regional and global efforts to promote abstinence, monogamy, and the use of female condoms have not only proved ineffective but also there had been no practical methods in most settings.
This has prompted the need for research based on effective prevention strategies that women can control themselves.
Products
As such, vaginal microbicides are HIV prevention products being developed for women.
To date, clinical trials had focused on microbicides formulated as vaginal gels, with tenofovir gel showing particular promise.
In a trial called CAPRISA 004, HIV risk was reduced by 39 per cent among women who used tenofovir gel before and after sex compared to women who used a placebo gel (a substance used in research which looks and feels the same as the active product, but does not contain any active ingredients and it is used as a comparison with the active substance).
The MTN is evaluating the daily use of tenofovir gel, as well as the daily use of the ARV tablets tenofovir or Truvada, in a large scale effectiveness trial called the Vaginal and Oral Intervention to Control the Epidemic (VOICE).
Depending on the results of VOICE and of FACTs 001, a study testing the same regime used in CAPRISA 004, tenofovir gel can be the first prevention product approved for use by women.
Experiences in areas of female contraception has demonstrated that women’s preferences differ, and that a product that best suits a woman’s life style and needs is more likely to be used.
And only if a product is used, does it have a chance of being effective.
This is why is it is important to investigate different prevention strategies.
For example, some women may even prefer taking tablets or prefer using a vaginal microbicide gel either daily or prior to sexual encounter, while others may prefer a product like a microbicide ring that feasibly, could be used and replaced once a month.
Study
A Study to Prevent Infection with a ring for Extended Use (ASPIRE) is a phase three safety and effectiveness study on the development and use of Dapivirine Vaginal Ring for HIV prevention for women.
ASPIRE is a combination of a large body of researchers looking at the Daprivirine ring as an alternative HIV prevention method for women.
The study is designed to provide the strength of evidence of support to potential licensure of the product.
In conjunction with data from long-term safety trial that the International Partnership for Microbicides (IPM) plans to conduct in parallel, regulators could consider approving the daprivirine ring for its wide-spread use if ASPIRE finds it safe and effective.
And should the tenofovir gel receive the desired approval, as is hoped, dapivirine ring could quite possibly represent a different HIV prevention option available to women.
ASPIRE is also referred to as Microbicide Trial Network (MTN) 020, a phase three study that seeks to determine whether a woman’s use of a vaginal ring containing antiretroviral (ARV) drug dapivirine is a safe and effective method for protecting against HIV infection.
The study is set to enroll approximately 3,457 women at several sites in Africa beginning 2012, and this study is set to last for a period of two years, with results anticipated late in 2014 or early 2015.
The study’s protocol is chaired by the University of Washington, (US) and co-chaired by Wits Reproductive Health Institute of South Africa.
The Daprivirine vaginal ring concept was developed by the IPM and is set to be tested in the ASPIRE project study, while IPM reserves the sole rights of sponsor and license holder of the product.
Vaginal rings intervention in the prevention of HIV is products designed to allow for the slow delivery of a drug or multiple-drugs over a period of weeks or months.
As a potential method for preventing sexual transmission of HIV, the rings are viewed as an alternative to microbicide gels, which are applied daily or prior to each sexual encounter.
The Dapivirine Vaginal Ring currently being tested in the ASPIRE project has an advantage over the microbicide vaginal gel because the ring, once inserted, is designed to work over a period of about four weeks before it can be replaced.
ASPIRE is the first phase III trial of a vaginal ring for HIV prevention and the first study to evaluate the effectiveness of a long-acting product intended for extended use.
It is also the first ever effectiveness study of an ARV-based HIV prevention product using a drug other than tenofovir (One of the drug combinations used in ARV drugs) or a tenofovir-drug combination.
Study design
The ASPIRE study will be randomly assigned to use either the Dapivirine ring or a placebo ring that looks the same but contains no active drug.
Participants will be instructed on how to insert and remove the ring, which they will replace every four weeks.
The women who will participate in the study will volunteer to use the assigned product for at least one year, some for two years.
Risk Reduction
As part of the study package, all participants will receive ongoing HIV risk reduction counseling, condoms and diagnosis and treatment of sexually transmitted infections.
ASPIRE is also designed to assess women’s adherence to, and acceptance of, the dapivirine vaginal ring.
For women who may contract HIV during the duration of the study, researchers will try to determine if there is a relationship between drug levels in cells and tissues and HIV risk, as well as the nature and frequency of HIV drug resistance.
The study is expected to be conducted at MTN affiliated sites in Malawi, Uganda, South Africa, Zambia, and Zimbabwe.
Dapivirine, also known as TMC-120, belongs to a class of ARVs called non-nucleoside reverse transcriptase inhibitors (NNRTI) that bind to and disable HIV’s reverse transcriptase enzyme, a protein that HIV needs to replicate (make more copies of itself).
It was initially being developed by Tibotec Pharmaceuticals, a subsidiary of Johnson and Johnson based in Belgium as an oral therapeutic agent to be used in the treatment of HIV.
Early-phase clinical trials found dapivirine was safe and that it suppressed the virus in HIV infected individuals.
Like vaginal rings that are used for contraception and hormone replacement in the US and Europe, the dapivirine ring is made of an elastic silicone material. Its design allows for the delivery of dapivirine slowly over time.
In fact, studies have shown that the ring can deliver high concentrations of active drug to vaginal tissue for a month or longer, with only trace amounts of the drug being absorbed elsewhere in the body.
IPM’s studies have also shown that the ring is safe and well-tolerated by women and that its use is highly acceptable to women in Africa.
IPM recently completed another trial of the ring’s safety and acceptability among 280 participants in four African countries and results are expected later this year.
IPM is committed to making dapivirine available at the lowest possible cost in countries where women urgently need tools to protect themselves against HIV.
It is hoped that once fully developed and proved to be effective, the dapivirine ring, alongside vaginal gels, and other HIV prevention interventions, will positively impact on reducing the prevalence and new infections of HIV especially among the most vulnerable groups-the women.