Drug-laced vaginal ring offers hope in HIV prevention

Monday April 18 2016

A woman holding the dapivirine vaginal ring

A woman holding the dapivirine vaginal ring tested in the NIH-funded ASPIRE study. 

By Sandra Janet Birungi & Lillian Namagembe

Of the 400 people who get infected with HIV every day in Uganda, 60 per cent of them are women. This means every day, about 240 women get infected with HIV.
Despite the high risk factor, practical methods of prevention for women are non-existent. Unlike men who have circumcision that reduces the risk of acquiring the HIV virus by almost 60 per cent, women have been waiting for something tailormade to benefit them at their convenience.
Twenty eight-year-old Amina Nakayiza (not real name) in 2012 enrolled onto a clinical trial study meant to improve women’s chances of being protected against HIV.
The trial titled, ‘A study to prevent infection with a ring for extended use’ (ASPIRE), was being carried out in Malawi, South Africa, Uganda and Zimbabwe alongside another study; The Ring Study.

Scope
It involved the use of a vaginal ring filled with antiretroviral drugs inserted manually at the tip of the cervix through the vagina; the drugs are released into the body throughout the month and are meant to fight off the virus in case one has sex with an infected person.
Upon being inserted, it takes eight hours for the drug to circulate around the vaginal area to ensure protection and is refilled at the end of every month.

The experience
Nakayiza agrees that at first, she was nervous to use the ring because she was not so sure if it would work or not.
“I felt normal and was comfortable. At the time, my boyfriend and I had been using condoms mainly because we did not want to get pregnant. To prevent HIV, we were faithful to each other; but when I started using the ring, I enrolled onto family planning and kicked out the condom because I knew was safe,” Nakayiza explains.
Despite enrolling onto the study, Nakayiza says she decided not to inform her boyfriend and he still doesn’t know she was protected against the virus during the time of the research (about two years ago).

Composition
Nakayiza is one of the 2,629 women in Malawi, South Africa, Uganda and Zimbabwe aged between 18 and 45 who enrolled onto the three year ASPIRE study. Results from the study revealed that if used consistently, the ring would protect on average up to 37 per cent of the women.
In explaining the significance of the results, Dr Flavia Matovu Kiweewa, the principal investigator of the ASPIRE study at the Makerere University – Johns Hopkins University (MU-JHU) Research Collaboration, Mulago, Uganda said if 100 infections were to occur, 37 of them would be averted by the ring.
“When carrying out clinical trials, we give half of the people rolled onto the study the drug in question and in this case it was the ring with the drug, dapivirine and the other half get the ring without the drug. This is done to compare results of both groups; whether one has the ring or not, people are sexually active and it is important to monitor both groups. We choose randomly who gets the active ring with the drug and who gets the one without or the placebo ring,” Dr Kiweewa explains.

“Results showed that in the placebo group, 97 HIV infections took place while in the active ring, 71 occurred. This means that if those with the active ring did not have it, 26 more infections would have happened. This means that the ring protected up to 26 per cent but when sites with poor adherence were removed, the protection went higher to 37 per cent; 54 infections took place in those on the active ring and 85 in those with the placebo ring,” she adds.
The results improve with age however. In women aged 25 years and above, the ring protected them up to 61 per cent, a significant improvement from circumcision which protects only between 50 to 60 per cent. For those aged 18 to 21 years of age, the ring showed no protection over all, Dr Kiweewa continues.

How it works
She cites adherence as a very important factor for the difference in the results. She adds that whereas circumcision is a one off exercise, the ring would require monthly refills for protection.
“The most important issue here is the fact that the ring if used could avert about 29,200 infections every year. This is because for every three infections that would have taken place, one is averted by the ring if we are to use the 37 per cent average. Therefore, of the 240 infections in women that would have occurred, 80 would be averted. It may look small on an individual basis but on a population level, it would be of more use,” Dr Kiweewa explains.

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In using the 61 per cent average for women above the age of 25, the ring would avert 144 new infections in women every day and 52,560 every year.
The Ring Study on the other hand enrolled 1,959 HIV-negative women aged 18-45 in South Africa and Uganda. Trials began in 2012 and ended in 2015. The study was done as a Phase III trial to confirm the results of the ASPIRE study. The Ring Study found that the ring protects by 31per cent overall and 37 per cent for women above 21 years of age.

Target group
Dr Annalene Nel from International Partnership for Microbicides (IPM) said the study targeted women in Africa because they have a higher risk of HIV infection mainly because of unprotected sex.
“Women have limited options; abstinence, monogamy and use of male condoms are not realistic or practical for many women yet daily oral ARV pills known as PrEP still remain a new method and may not be easy for some women to use. The flexible ring is easy for a woman to insert herself and provides sustained-release of dapivirine locally to the site of potential infection during vaginal sex,” Dr Nel explains.

Outcomes
Dr Kiweewa says the ring was not designed to protect 100 per cent but rather hope it would protect at least 60 per cent which was achieved for the women above the age of 25.
Most importantly, the study showed that the ring was safe to use and had no adverse effects on all who used it. Pregnancy incidence was similar in both groups with the active ring and the placebo ring which means that it would not affect pregnancy although it is not conclusive on what happens if one gets pregnant with the ring.

Godfrey Kalema, a partner to one of the users says he didn’t know his wife had started using the ring because it was business as usual in the bedroom for them.
“I got the information from one of her friends but I have to say I was impressed with the ring. It is not like a condom which you have to put on every time you have sex, it is monthly and you do not even feel it,” Kalema explains.
Results from both studies were announced in February at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, Massachusetts.

Way forward

The ring was developed by International Partnership for Microbicides. Dr Jared Baeten who led the ASPIRE study at Microbicide Trials Network (MTN), said by late 2018 or early 2019, the ring would be available for usage after being licensed. Its regulatory sponsor, IPM, is going to submit information for a license.
Dr Kiweewa adds that steps are being taken to ensure that all women involved in the studies are provided with the ring for protection. South Africa has already approved the use of the ring.
She continues to say that further studies are going to be carried out to find out the ring’s effectiveness for adolescents who were not involved in the study despite being sexually active.

The ring is expected to cost $5 (about Shs3,400) although the price is expected to reduce if donors come in.
Dr Nuru Bulya Semiyege, of Infectious Diseases Institute says the Ministry of Health should consider enrolling the ring to the public, once it is licensed, because of its effectiveness; as well as Oral Pre-exposure prophylaxis which can be used to prevent HIV infection for those aged between 18 to 24 years.
Nakayiza tested HIV negative after the end of the study and she says now that the ring is out of the picture, she still hopes that being faithful in her relationship will protect her further from acquiring the virus.

editorial@ug.nationmedia.com

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