Frequently Asked Questions
What is The Ring Study?
The Ring Study is a clinical study evaluating whether a monthly vaginal ring that contains the antiretroviral (ARV) drug dapivirine is safe and effective in preventing HIV in women when compared to a placebo vaginal ring (that does not contain dapivirine). The study aims to enroll approximately 1,650 women ages 18-45 and is currently enrolling participants at four sites in South Africa. The Ring Study (also known as IPM 027) is being conducted by the International Partnership for Microbicides (IPM), a nonprofit organization, in collaboration with local research centers in each of the participating countries.
What is a vaginal ring?
Vaginal rings are products designed to continuously deliver a drug or multiple drugs inside the vagina over a period of weeks or months, and are currently used for other medical purposes, such as contraception and hormone replacement. IPM adapted this technology to the fight against HIV with its development of a novel microbicide ring that releases the ARV dapivirine over time. The Ring Study is testing a microbicide vaginal ring replaced each month as a potential method to prevent women from becoming infected with HIV. Several previous studies showed that women find the ring to be highly acceptable as did select male partners who were interviewed.
How does The Ring Study fit into IPM’s ring licensure program?
The Ring Study is part of a broader licensure program being conducted by IPM in partnership with the National Institutes of Health-funded Microbicide Trials Network (MTN). The full dapivirine ring licensure program includes IPM’s Ring Study as well as MTN’s ASPIRE study (MTN-020), which began in July 2012. Together, the studies will involve thousands of female volunteers across Africa and aim to evaluate the ring’s ability to prevent new HIV infections in women as well as its long-term safety. The licensure program will also include several smaller studies to examine the ring’s safety in adolescents and women over 45, condom compatibility and possible drug-drug interactions. The package of studies in the dapivirine ring licensure program are designed to provide the strength of evidence required to support the ring’s approval by regulatory authorities for licensure as a new HIV prevention option for women.
Why is The Ring Study important?
Globally, HIV/AIDS is a leading cause of death among women, taking an especially high toll in sub-Saharan Africa, where women account for approximately 60 percent of all people living with HIV. Women are particularly vulnerable to infection due to a mix of biological, economic and social factors, and urgently need female-initiated prevention options to protect their own health. IPM has developed a discreet and easy-to-use microbicide ring to help address this critical gap in HIV prevention. IPM’s monthly ring provides a long-acting alternative to other microbicide formulations being studied that are designed to be taken daily or around the time of sex. Women need more than one HIV prevention option, so they can choose according to their individual needs and preferences.
What drug is being used in The Ring Study?
Dapivirine, the drug currently under evaluation in The Ring Study, is similar to ARVs currently used to treat HIV/AIDS and to prevent mother-to-child transmission (PMTCT). It is being developed exclusively as a microbicide ring to help protect women from HIV infection during sex with a male partner. Dapivirine
belongs to a class of ARVs known as non-nucleoside reverse transcriptase inhibitors, or NNRTIs, which work against HIV-1 by preventing the virus from making copies of itself once inside a human cell. Dapivirine was first evaluated as an oral therapeutic by Janssen R&D Ireland (previously Tibotec
Pharmaceuticals), one of the Janssen pharmaceutical companies of Johnson & Johnson. It was then licensed to IPM for further testing as a microbicide. To date, dapivirine has been found to be safe and well-tolerated in more than 25 clinical safety studies conducted in Europe, the United States and Africa. These studies tested dapivirine in three different forms: an oral tablet, vaginal gel and vaginal ring.
What are the main goals of The Ring Study?
The Ring Study is a randomized, double-blind, placebo-controlled clinical study designed to determine the efficacy and long-term safety of the dapivirine vaginal ring in the prevention of HIV-1 when used every four weeks for two years. In addition, the study will assess how well women like using the ring (acceptability) and if women use the ring as intended (adherence). Data will also be collected on the rates of sexually-transmitted infections, HIV-2 infection, and pregnancy occurring during the study as well as the frequency of drug resistance in women who become HIV-1 positive during the trial.
Where is The Ring Study taking place?
The following research centers are currently implementing The Ring Study:
- Madibeng Centre for Research, Brits, North-West, South Africa
- Qhakaza Mbokodo, Ladysmith, KwaZulu-Natal, South Africa
- Maternal, Adolescent and Child Health (MatCH), Edendale, KwaZulu-Natal, South Africa
- Prevention of HIV/AIDS Project (PHIVA), Pinetown, KwaZulu-Natal, South Africa
How long is the study expected to last?
The Ring Study began in April 2012 and is continuing to enroll participants in 2013. Each participant will be enrolled in the study for two years plus an additional six weeks of follow-up. The data will then be analyzed and the results are expected to be released in late 2015.
What is being done to ensure the safety of the participants in The Ring Study?
Protecting the health and safety of the women who volunteer for the study is IPM’s top priority. Before participants in clinical studies use any new product, extensive preclinical studies are conducted in the laboratory and in animals to identify the product’s safety profile. Only products that are proven safe in these preclinical tests progress to clinical studies. IPM has completed six clinical safety studies of different formulations of the dapivirine ring, all of which showed the ring to be safe and well-tolerated.
The Ring Study is approved by national regulatory agencies and local ethics committees before research centers begin the study. IPM closely monitors the study to ensure that all operational and safety procedures are implemented according to the study protocol. In addition, study participants receive medical treatment at the research centers or are referred to local health services as appropriate for medical conditions. Moreover, all study participants receive regular medical exams, HIV and STI testing and risk reduction counseling, and access to free male condoms at every study visit.
In addition, an independent Data Safety Monitoring Board (DSMB) will conduct regular reviews of the study data to ensure the safety of participants at all times. If any safety concerns arise or if the study becomes unable to answer its main objectives, the DSMB may, at any time, recommend modifying or stopping the study to protect the safety and well-being of the participants.
Will women provide informed consent to participate in the study?
Yes, all women who volunteer to participate in The Ring Study will provide informed consent before enrolling in the study. The informed consent process is crucial to ensuring all participants receive detailed information about the study and understand the potential risks and benefits of participation. Informed consent occurs at the first screening visit, once again when a participant decides to enroll, and is revisited throughout the duration of the study. Women may choose to leave the study at any point for any reason, with no consequence. Informed consent forms and any other study-related materials are translated into appropriate local languages for each site. For non-literate volunteers, informed consent documents and other written materials are read to the participant in her preferred local language. These participants will indicate consent verbally and provide a thumbprint, as verified by an impartial witness.
What if a woman becomes pregnant during the study?
Women who plan to become pregnant during the study time frame should not volunteer for the study. Pregnant women and women who are breastfeeding at the time of screening are not eligible to enroll in the study. Women who volunteer for the study are required to be on a stable method of contraception, and those who join the study will receive ongoing contraceptive counseling, access to free condoms and will be tested for pregnancy at each study visit. If a woman becomes pregnant during the study, she will stop using the ring immediately and will be referred to a local health facility for prenatal services.
What if a woman becomes HIV positive while in the study?
Women in the study receive ongoing and thorough counseling on reducing their risk of acquiring HIV and other STIs, and will be provided with condoms at each visit to the research center. Because condoms are currently the best way to prevent transmission of HIV during sex and it is not yet known whether the dapivirine ring will protect against HIV, all participants are strongly encouraged to use a male condom during sex. However, using a condom is not always possible and a woman could acquire HIV if she has unprotected sex with a partner who is infected with the virus.
If a participant becomes HIV positive during the study, she will immediately stop using the ring to minimize the possibility of developing resistance to dapivirine and other similar drugs. She will also be counseled and referred for support services, and for appropriate HIV-related care and treatment at local public health facilities. Each research center has strong linkages and referral agreements in place with local organizations that provide support and medical services. Women who become HIV positive during The Ring Study will also have the option to enroll in a separate long-term follow-up study to assess the impact, if any, of the microbicide on HIV treatment outcomes.
Why is this study being done in Africa?
Africa bears a disproportionate burden of the HIV/AIDS epidemic, with over two-thirds of the global burden in sub-Saharan Africa. Sixty percent of people infected with HIV in Africa are women and girls, and they desperately need a female-initiated prevention strategy to protect themselves. The Ring Study is conducted in Africa to ensure the product is safe and acceptable to the populations that need it most.
If the dapivirine ring is shown to be safe and effective in preventing HIV, what will be done to make the product available to the women who need it?
IPM is now laying the groundwork to help ensure that women would have rapid and affordable access to the dapivirine ring should the package of studies in IPM’s licensure program support its efficacy and long-term safety. IPM, in collaboration with key partners, is addressing issues surrounding access and will continue to engage in strategic planning throughout the ring licensure program to expedite the product’s roll-out and availability to women in developing countries.