HIV Prevention Ring Passes Safety Testing Clinical Trial

Young girls, especially those who live in areas where HIV is epidemic, like sub-Saharan Africa, are particularly vulnerable to becoming infected with HIV. A vaginal ring containing the antiviral agent dapivirine has been shown to decrease the chance of developing HIV-1 in adult women over 21 and now in the first step for use in adolescents, the ring has been shown to be safe and well-tolerated in that younger age group.

"HIV doesn't distinguish between a 16-year-old and an 18-year-old," study author Sharon Hillier said in a press release. "Access to safe and effective HIV prevention shouldn't either. Young women of all ages deserve to be protected."

The previous clinical trials that showed decreases in HIV infections in women over age 21 did not show protection in women ages 18–21. Lack of protection for women in that age group was attributed to the fact that many of those women did not use the ring properly and as instructed to achieve the best results. The new study was conducted in the US on young women in an attempt to show whether the ring would be safe and work for them if used properly.

Results of safety and acceptability of using the ring were reported July 25 by the study investigators at the 9th IAS Conference on HIV Science in Paris.

Targeting Women to Prevent HIV

Adolescents are particularly vulnerable to becoming infected with HIV. Some reasons why include high-risk behavior like drug or alcohol abuse, early or promiscuous sexual activity, and general lack of information about the infectious process and how to protect themselves. According to the Centers for Disease Control and Prevention, about 50,000 new HIV infections were diagnosed in the US 2010 and about 26% of those were in the 13–24 age group.

HIV Prevention Ring Passes Safety Testing Clinical Trial — Electron microscopic image of HIV viruses. *Image by A. Harrison and P. Feorino/CDC*

Nowhere are the infection rates higher than in Africa, where about 70% of the people in the world with HIV live. The fatal consequence of untreated HIV is Acquired Immune Deficiency Syndrome (AIDS) — a failure of the immune system leading to death by infection. AIDS is the number one leading cause of death in people aged 10–19 in Africa. AIDS-related deaths in kids between 15 and 19 doubled from 2000 to 2016.

Young girls are especially vulnerable. Globally, girls account for 65% of new adolescent infections, but in 2015 that number was 75% in sub-Saharan Africa.

Because of clinical availability and other socio-economic factors, only about 13% of adolescent girls and 9% of adolescent boys between the ages of 15 and 19 living in sub-Saharan Africa were tested for HIV in the last year.

When young people aren't getting diagnosed, treatment can't help them; education about prevention methods hasn't fixed the problem. The new vaginal ring holds real promise to make progress on staving off infection.

How the Ring Works

The vaginal ring was developed by the International Partnership for Microbicides, a nonprofit organization with offices in the US, South Africa, and Europe. The ring slowly releases HIV drug dapivirine into the vagina over the month it is in use. Dapivirine is an anti-retroviral drug — it specifically targets the mechanisms that HIV and other retroviruses. It works by inhibiting HIV's reverse transcriptase enzyme, a protein vital to HIV's ability to replicate and cause an infection.

The dapivirine ring is made of a flexible material, and is inserted by the user and replaced monthly. When in place, it sits high in the vagina, much like intravaginal contraceptive rings.

The ring was developed and designed to be an easy-to-use intervention that women can control themselves, and be longer-acting and applied in advance, and to deliver an anti-HIV drug at the point the virus enters a woman's body.

The Clinical Trials

The new study, known as MTN-023/IPM 030, was designed to provide information about how well girls under 18 years old tolerate the vaginal ring and how safe it was for use in this age group.

The researchers enrolled 96 sexually active females aged 15 to 17 in the study. They were split randomly into two groups: two-thirds of the girls were assigned to get the dapivirine ring and one-third got a placebo, a ring that did not contain any medication. New rings were inserted monthly for six months. The researchers drew blood from the young women as a means to confirm that the rings were being used and replaced as instructed. The participants reported side effects from the ring to the research team and completed surveys on the computer about their experience using the ring.

There were no differences in side effects reported by young women using the dapivirine ring and those using the placebo. Blood drug levels showed that 87% of the girls in the dapivirine group were using the ring. The study participants reported no discomfort due to the ring at 87% of visits and "liking" the ring at 93% of visits. The concern voiced most often — by 28% of the women — was that their sex partner might feel the ring during sex.

The study investigators concluded that the ring is safe and acceptable to young women and the results showed that the women were using the device. Discussing the concerns about comfort with a partner before sex may help couples continue to use the ring.

Two other studies — clinical trials — of the dapivirine ring have been done. The studies are nicknamed ASPIRE and The Ring Study. Their objectives were to monitor the safety of the device and to see if the use of the ring is effective in preventing HIV infections in 18 to 45-year-old women in Malawi, South Africa, Uganda, and Zimbabwe. Those two trials enrolled a combined total of over 4500 women.

Results of ASPIRE and The Ring Study were reported in February 2016. Use of the ring reduced the risk of acquiring HIV by 27% in the ASPIRE study and by 31% in The Ring study. Women 21 and older and those who used the ring regularly had higher levels of protection against contracting an HIV infection. The ASPIRE data showed that the ring protected 61% of the women aged 25 and older from HIV; that number rose to 75% for those who used the ring exactly as prescribed.

The Microbicide Trials Network, funded by NIH, conducted the studies. They plan to start another clinical trial later this year, called REACH. REACH will collect safety data on about 300 girls aged 16 to 21 in the HIV high-risk country of Africa. Additional clinical trials in young women will have to be done to be sure that the ring reduces the risk of HIV infections in young women of those ages before a request is made to approve the ring for use in women of those ages.

The International Partnership for Microbicides is pursuing regulatory approval of the dapivirine ring for women ages 18-45, the ages studied in the ASPIRE and The Ring Study trials. The first regulatory approvals in African countries could be received as soon as early 2019.

It may not be long before a preventative easy-to-use method can be implemented globally and across many age groups of women to start to change their HIV infection statistics for the better.