Monthly vaginal rings move one step closer to becoming a new HIV prevention method

Reviewed by Emily Henderson, B.Sc.July 24, 2020

A vaginal ring intended to be used for one month at a time is a new HIV prevention method for sub-Saharan South African sigender women with few options to protect themselves in the face of an epidemic We are one step closer to the possibility of becoming infected.

The ring, which women can insert and replace by themselves, slowly releases an antiretroviral (ARV) drug called dapivirine into the vagina (the site of possible HIV infection) during the month of wear. The nonprofit International Microbicide Partnership (IPM) has developed and is seeking approval for a monthly Dapivirine Ring.

Today’s announcement that the European Medicines Agency (EMA) has adopted a positive scientific view on the use of rings in low- and middle-income countries is a big step towards the potential approval of the Dapivirin ring in African countries. IPM is currently working with the World Health Organization (WHO) to file applications with national health regulators in eastern and southern Africa and the US Food and Drug Administration later this year.

In parallel, the WHO has revised its HIV/AIDS treatment and prevention guidelines with evidence-based recommendations for policy makers and health care providers regarding the use of rings and is a global quality assurance designation, “pre-certification”. Is expected to make a decision.

With the exception of condoms, the only other HIV prevention products ever approved include daily use of ARV pills, oral pre-exposure prophylaxis, or an approach called PrEP.

If approved, Dapivirin Ring will be the first biomedical prophylaxis, especially for women with cis gender, and the first long-acting method. The point is that women can choose the method that works best for them.

This is a long way and we have never reached the final goal of providing multiple options for women at risk for HIV. But this positive opinion from EMA makes us more intimate than ever. This is a remarkable achievement for women’s HIV prevention and bears an IPM for its scientific leadership, vision and solid advocacy. MTN is honored to play a role in this effort and we thank the research teams from both organizations and research participants to reach today. “

Dr. Sharon L. Hillier, Professor and Vice Chair of the Department of Obstetrics and Gynecology and Reproductive Science, School of Medicine, University of Pittsburgh, and Principal Investigator (MTN) of the National Institutes of Health (NIH)-funded bactericidal testing network

As a clinical partner for IPM, MTN has conducted some of the research included in IPM’s submission to EMA and will be included in other regulatory submissions.

The ring review by the EMA was conducted in collaboration with WHO through a procedure called Article 58, primarily for products used in low and middle income countries. Reviews are conducted with the same rigor as products sold in the EU.

Application of IPM to EMA includes data from 183 non-clinical trials, 11 Phase I and II safety and pharmacokinetic studies, and two Phase III trials: IPM-led The ring test (IPM 027), and ASPIRE (MTN-020), MTN, and two Phase IIIb Open Label Extension (OLE) studies, HOPE (MTN-025) and DREAM (IPM 032) were conducted. Two Phase III trials involved more than 4,500 cis-gender women aged 18 to 45 in Malawi, South Africa, Uganda and Zimbabwe. Their results were reported in 2016, and the Dapivirin ring was well tolerated and helped reduce the risk of HIV by about 30%. Higher levels of protection were found in women who used the ring most often. Results from the OLE study suggest a greater risk reduction (approximately 50%), but the lack of a placebo arm makes these findings less reliable. The additional data provided during the EMA review showed that Dapivirin Ring reduced HIV risk in women by 35%, with no safety concerns from long-term use.

Of the 11 supported studies reviewed by the EMA, three were conducted by MTN and all were conducted at US clinical research sites. These include a Phase IIa safety study of adolescent girls (MTN-023 / IPM 030) and postmenopausal women (MTN-024 / IPM 031), and safety and pharmacokinetic studies of breastfeeding women (MTN-023). -029 / IPM 039) is included. Three additional MTN studies provided supplemental information. MTN-012/IPM 010, Phase I Penis Safety Study. MTN-013 / IPM 026, which augments the data on the safety and pharmacokinetics of dapivirin rings. MTN-015: Observational study of women infected with HIV while participating in ASPIRE and HOPE.

MTN is also currently conducting a ring safety study in these groups, as the initial approval of rings by African regulators does not apply to girls under the age of 18 or to pregnant or breastfeeding women. May be approved for use by these groups in the future.

HIV prevalence is particularly high among most adolescent girls and young women in Africa, and among pregnant and lactating women, and may be two to four times more likely to be infected with HIV. there is.

REACH (reversing the African epidemic with HIV prevention options), or MTN-034, is being tested in four clinical trial sites in South Africa, Uganda, and Zimbabwe, including 185 people under the age of 18 and 247 people aged 16 to 21. Registered participants. The expected REACH results in 2022, and the results of the MTN-023/IPM 030 study conducted in the United States on adolescent girls aged 15 to 17 years, show the IPM’s decision-making on regulatory requirements. It is expected to provide the necessary safety data to guide the approval of this group in the coming years. REACH also helps to understand how to best support young women and girls to use rings and PrEP as much as possible. This can be important for the wider implementation of these methods.

The DELIVER (MTN-042) study for pregnant women and the B-PROTECTED (MTN-043) study for breastfeeding women are being conducted at four sites in Malawi, South Africa, Uganda and Zimbabwe. Launched in February 2020, DELIVER has been open on one site so far. The B-PROTECTED study is pending national and ethical approval and will begin in the coming weeks.

“These are one of the people who need the most HIV prevention tools, but they’re often overlooked in clinical trials of investigational drugs. We can’t wait to see if the ring will be approved. It is ongoing in parallel with the review process,” said Jared Baeten, MD, Professor of Global Health, Medicine, and Epidemiology, School of Public Health, University of Washington, Seattle. Co-Principal Researcher of MTN.

“In the end, we hope to make the ring available to all women, regardless of age or birth status,” he added.

No single HIV prevention method works for everyone. Women’s needs and preferences are different and can change over time. As with contraception, the more HIV prevention options available to women, the more likely and likely they will be.

Oral PrEP is very effective, but only if taken daily as directed. This may be difficult for some people or undesirable. If approved, a monthly dapivirine ring will be given to women who do not consistently use daily oral PrEP, or who choose to not use products that deliver drugs systemically in another option.

“I’m excited about the positive opinion from the EMA about the Dapivirin Ring. So do many women and research teams who have participated in our study. But serious about reducing women’s HIV prevalence. We need to offer multiple options beyond just oral PrEP and vaginal rings. This is a huge step forward, but we need to continue our work in this area.” Thesla Palanee-Phillips, MMed Sci, PhD, MSc. , Led the ASPIRE study with Dr. Baiten of the Wits Reproductive Health and HIV Institute in Johannesburg, South Africa.

“Expanding the number of HIV prevention options is important for women here in Africa and globally.”