Vaginal. Women appreciated the discretion and long-acting action of the Vaginal Ring.
Dapivirine vaginal ring (Image: The NIAID)
An update of the analysis from adherence to 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 AIDS Conference XXI (AIDS 2016) in Durban. In addition, African women who participated in the study told the researchers that they liked the product, found it is easy to use and preferred over possible alternatives such as pills or vaginal gels.
The ASPIRE Study evaluated the effectiveness of a vaginal ring impregnated with the anti-drug HIV dapivirine. A ring that is similar to the devices used in contraception, was designed to be used inside the vagina for one month; women can insert and remove. This study recruited 2629 women in Malawi, South Africa, Uganda and Zimbabwe.
The study's findings, released in February, were somewhat disappointing - an overall reduction in infections of 27%, but this result was masked, a higher level of effectiveness among the elderly participants in the study, which may have had higher levels of adherence than than younger participants. Stratified by age, the vaginal ring had zero efficacy for women aged 18 - 21, and a reduction of infections by 56% in women aged 22 to 26, and a reduction of infections by 51% among women with 27 years or more.
In Durban, Elizabeth Brown of the University of Washington presented a new analysis in which they tried to correlate effectiveness with different levels of adherence. Considering that previous analyzes have assessed adherence by measuring blood levels of dapivirine, this may reflect the ring only being inserted the day before a visit to the clinic. The new analysis focused on the level of the drug remaining in the rings that were returned to researchers after use, giving a better indication of adherence throughout the month.
Before use, the rings contain 25 mg dapivirine. As a ring that has been worn for an entire month should have 20 - 21 mg of the 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 the drug indicates non-adherence.
- Periods with non-adherence represented 33% of the follow-up. As expected, there was no statistically significant reduction in HIV infections during these periods.
- Periods with medium to high adherence represented 42% of follow-up. Used rings are reducing the rate of HIV infections by 65%, compared to the control group, which received rings with placebo. A note from the editor: I’m not really a researcher, so I can’t stop thinking if there’s no better way to perform these tests, if, for example, research without a “control” group that is literally being subliminally induced to behavior that she would not adopt if she did not believe she had a “device that would protect her 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.
Then he looked at adherence two or three months before HIV infection (instead of just a month in advance).
Thus, these analyzes suggest that the effectiveness for women with the highest level of compliance may be 75% or 92%.
In addition, non-adherence periods appeared to represent a smaller proportion (20%) of time.
“It was clear that, through multiple analyzes, there is a statistically significant relationship between the use of the vaginal ring and protection against HIV infection”.
Thus, the researchers concluded:
"These analyzes provide evidence suggesting a defensive 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 insights into the experience of women wearing rings, vaginal delivery and their appreciation of the product's qualities. Elizabeth Montgomery and Ariane van der Straten from 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 of the 15 study sites. Their demographics largely reflect the largest studies: average age of 26, 45% were married, e 73% had completed secondary education.
The ring was considered simple and discreet, as this woman explained:
“I like them very much because once they wear out, you don't feel it, and no one can suspect that you are wearing something. I like it because nothing changes about how we live as women. ”
While some women had initial concerns about the appearance of the ring 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 can be important if 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, due to the size of the ring… during 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 easy to use. ”
The researchers asked some women to compare it with other forms, other than vaginal rings in which the prevention drug could be delivered - oral pills, implant injections, vaginal suppositories, vaginal films and vaginal gels. Women are often the preferred methods that have been known to them - vaginal rings had been used as part of the study ASPIRE or products similar to the contraceptives they knew.
As women showed a tendency to appreciate long-acting products instead of those that needed to be reminded daily or applied at the time of sex.
"The ring is better than a condom because when you are going to have sex the ring is already inside you, unlike the condom you have to put on before each sexual act."
However, there could be some anxiety about side effects, invasiveness and the lack of reversibility of long-acting products.
"I am afraid ... I don't know how [the injection] will be like inside my body, I don't know if it will affect my health".
These concerns about vaginal rings lessened 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 on and take off constantly, for some participants, especially those under 25 years old. Some women remove the vaginal ring during menstruation.
Women describe negotiating the use of the vaginal ring with male partners. Partners generally had an influence, positive or negative, on women's attitudes and wearing the ring.
“No, I told you to take the ring as a condom. I said: “Because you don't want us to use a condom, this is now our condom, just ignore it, it's inside my body and the body is mine. Because you don't want the condom to think that this is my condom because you don't want to use a condom, I'm using mine. ” We never had any problems about it and we never talked about it again. ”
Women might be concerned and feared that a partner might feel the ring during sex.
"Sometimes you are your partner and he stimulates you with his finger and finds a ring, so that is followed by twenty-one questions."
Montgomery told AIDSMAP said that some participants and their “doubts about the research process may have contributed to less adherence. Women expressed concerns about not knowing whether they had received a ring with the active component […] or a placebo ring, the efficacy and safety of the unknown ring and the idea of being "researched". Therefore, taking part in a placebo-controlled study may have had an impact on not using the ring. NE: Which is perfectly understandable!
Human Guinea Pigs - In my view, this becomes a procedure close to homicide or, at the very least, the risk of life.
Why don't they test on American, German or French women?
Because Africa, the crowded place, has to pay taxes, naturally.
However, many women said they enjoyed taking part in the study. They felt that they were part of a "team" and were doing something for the "greater good". They estimated the health care and other benefits that the study provided. Of course, this could have influenced some of the women's responses during the interviews.
In studies of oral pre-exposure prophylaxis (PrEP), adherence tends to be better in open studies than in the original study placebo-controlled. The context of these studies can address some of the concerns about the research process mentioned above - the participants were unaware that they are receiving an active product and that it has proven to be effective and safe. Studies are closer to real-world conditions than those of placebo-controlled. In the case of oral PrEP, higher levels of effectiveness have been demonstrated. [NE: Therefore, placebo-controlled studies should be abolished, as they do not represent, as the text itself says, corresponding to the "real world"]
Given this placement, participants in the ASPIRE study are now being asked to enroll in a follow-up study of the vaginal ring with dapivirine. Women who participated in the Ring study (another randomized study of the same product) will also be invited to participate in an open study. The International Partnership for Microbicides is hopeful that regulators will be able to 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. Reviewed by Mara Macedo.
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E Brown, T Palanee-Philips, 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.
And 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.
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