Women enjoyed discretion and action over time Vaginal Ring
Dapivirine vaginal ring (Image: The NIAID)
An update of the analysis from accession in the ASPIRE study indicates that consistent use of a vaginal ring containing dapivirine showed that there were 65% fewer HIV infections, according to a presentation at the recent International Conference on AIDS XXI (AIDS 2016) in Durban. In addition, African women who participated in the study told the researchers that they liked the product, found it easy to use and preferred in relation to possible alternatives such as tablets or vaginal gels.
The ASPIRE study evaluated the effectiveness of a vaginal ring impregnated with the anti-HIV drug dapivirine. The ring that is similar to the devices used in contraception, was designed to be worn inside the vagina for a month; women can insert and remove. The study recruited 2629 women in Malawi, South Africa, Uganda and Zimbabwe.
The study's findings, released in February, were somewhat disappointing - a global reduction in 27% infections. But this result was masked, a higher level of efficacy among the elderly participants of the study, who may have had higher levels of adherence than younger participants. Age-stratified, the vaginal ring had zero efficacy for women aged 18-21, and reduction of 56% infections in women aged 22 to 26, and reduction of infections in 51% among women with 27 years or more.
In Durban, Elizabeth Brown of the University of Washington presented a new analysis in which they attempted to correlate efficacy with different levels of adherence. Considering that previous analyzes evaluated adherence by measuring levels of dapivirine in the blood, this may reflect the ring only being inserted the day before a visit to the outpatient clinic. The new analysis focused on the level of drug remaining in the rings that were returned to the researchers after use, giving a better indication of adherence throughout the month.
Before use, the rings contain 25 mg of dapivirine. As a ring that was worn for a whole month must have 20-21 mg remaining drug, any level below 22 mg was treated as an indication of medium to high adherence. A ring with 23,5 mg or more of drug indicates nonadherence.
- Non-adherence time periods accounted for 33% of follow-up. As expected, there was no statistically significant reduction of HIV infections during these periods.
- Periods of time with medium to high adherence represented 42% follow-up. Rings used are reducing the rate of HIV infections in 65%, compared to the control group, which received rings with placebo. [An editor's note: I'm not really a researcher, so I can not stop thinking if there is not a better way to do these tests, if, for example, searching without a "control" group that is literally being subliminally induced to behavior that he would not adopt if he did not believe he had a "device to protect him from the risk of contracting HIV. I consider this procedure unethical, inhuman and immoral ...]
The researchers also performed additional analyzes in an attempt to adjust the actual length of time between study visits and analyzed adherence two to three months before HIV infection (rather than just one month in advance). These analyzes suggest that the efficacy for women with the highest level of adherence may be 75% or 92%. In addition, periods of non-adherence appeared to represent a minor proportion (20%) of time.
"Through multiple analyzes, there is a statistically significant relationship between vaginal ring use and protection against HIV infection," the researchers concluded. "These analyzes provide evidence suggesting a dose-response relationship between the ring and HIV contamination."
Importance of partner education and attitudes
A qualitative component of the study, interviewing 214 participants, provides insight into the experience of women wearing rings, vaginal delivery and their appreciation of the qualities of the product. Elizabeth Montgomery and Ariane van der Straten of RTI International presented results on 2 posters.
The women who were interviewed (either in an in-depth interview, a series of in-depth interviews, or as part of a focus group) were recruited from 6's 15 study sites. Its demographics largely reflect the larger studies: the average age of 26, 45% were married and 73% had completed upper secondary education.
The ring was considered simple and discreet, as this woman explained:
"I really like them because once they wear out, you do not feel it, and no one can suspect you're wearing something. I like it because nothing changes about how we live as women. "
While some women had initial concerns about the ring's appearance and potential side effects, these problems were generally overcome through group discussions, counseling and increased familiarity with the product. Continuing to offer this type of support may be important if the vaginal rings are implemented.
"When you see the ring for the first time you are shocked. I thought it was too big and I almost left the study because of the size of the ring ... during the education I learned that the ring remained soft, I found that wearing the ring was difficult and painful. They showed that to insert the ring you just need to twist it making it look like an 8, and when I tried it it was easy and quiet to use it. "
The researchers asked some women to compare them with other, different forms of vaginal rings in which the drug's prevention could be delivered - oral tablets, injections, implants, vaginal suppositories, vaginal films and vaginal gels. Women are often the preferred methods that were known to them - vaginal rings had been used as part of the ASPIRE study or products similar to the contraceptives they knew.
Women tended to appreciate long-acting products rather than those that needed to be recalled daily or applied at the time of the transaction.
"The ring is better than a condom because when you are going to fuck it the ring is already inside of you, unlike the condom you have to put before every sexual act."
However, there could be some anxiety about the side effects, invasiveness and lack of reversibility of long-acting products.
"I'm Fearful ... I do not know how [the injection] is going to be like inside my body, I do not know if it's going to affect my health."
These concerns regarding vaginal rings decreased with teaching and through experience.
Several potential products (including rings, gels, suppositories and films) need to be applied inside the vagina and this was disconnected from the need to put and take constantly, for some participants, especially those with less than 25 years. Some women remove the vaginal ring during menstruation.
Women describe the negotiation of vaginal ring use with male partners. Partners generally had a positive or negative influence on women's attitudes and ring use.
"No, I told you to take the ring like a condom. I said, "Because you do not want us to use the condom, this is now our condom, just ignore it, it's inside my body and the body is mine. Because you do not want the condom to think this is my condom because you do not want to use a condom, I'm using my condom. "We never had a problem about it and we never talked about it again.
Women might have worried and feared that a partner might feel the ring during sex.
"Sometimes you're your partner and he stimulates you with a finger and finds a ring, so that's followed by twenty-one questions."
Montgomery told AIDSMAP that some participants and their "doubts about the research process may have contributed to lower adherence. Women expressed concerns about not knowing whether they had received a ring with the active component [...] or placebo ring, the proven effectiveness and safety of the ring unknown and the idea of being "searched". Therefore, taking part in a placebo-controlled study may have had an impact on non-use of the ring. (NE: What it is perfectly understandable! "Human Guinea Pigs - In my view it becomes a next procedure to murder or when little, the periclitação life. Because they do not test on American, German or French women? Because Africa has to pay taxes, of course)
However, many women said they enjoyed taking part in the study. They felt they were part of a "team" and were doing something for a "greater good." They estimated the health care and other benefits that the study provided. Of course, this might have influenced some of the women's responses during the interviews.
In studies of oral pre-exposure prophylaxis (PrEP), adhesion tends to be better in open studies than in the original study placebo-controlled. The context of these studies may address some of the concerns about the research process mentioned above - participants were unaware that they are receiving an active product and have proven to be effective and safe. Studies are closer to real-world conditions than placebo-controlled. In the case of oral PrEP, higher levels of efficacy have been demonstrated. [NE: Therefore, placebo-controlled studies should be abolished because they do not represent, as the text says, "real world"]
Given this placement, ASPIRE study participants are now being invited to enroll in a follow-up study of the vaginal ring with dapivirine. Women who participated in the Ring study (another randomized trial of the same product) will also be invited to participate in an open study. The International Partnership for Microbicides is hopeful that regulators can approve the vaginal ring with dapivirine in 2018.
Translated by Cláudio Souza from the original in AIDS 2016: Vaginal Ring for HIV Prevention is Effective and Acceptable written by Roger Pebody. Revisioned by Mara Macedo
E Brown, Palanee-Philips T, M Marzinke, et al. Residual dapivirine ring levels indicate higher adherence to vaginal ring is associated with HIV-1 protection. 21st International AIDS Conference. Durban, July 18-22, 2016. Abstract TUAC0105LB.
E Montgomery, A van der Straten, M Chitukuta, et al. Key insights into acceptability and use of the vaginal ring: results of the MTN-020 ASPIRE trial qualitative component. 21st International AIDS Conference. Durban, July 18-22, 2016. Abstract WEPEC265.
A van der Straten, MK Shapley-Quinn, K Reddy, et al. HIV pre-exposure prophylaxis (PrEP) formulation preference among women participating in the qualitative component of the ASPIRE (MTN-020) study. 21st International AIDS Conference. Durban, July 18-22, 2016. Abstract WEPDC0203