WHO today recommended that the dapivirine vaginal ring (DPV-VR) may be offered as an additional prevention choice for women at substantial risk[1] of HIV infection as part of combination prevention approaches.
The DPV-VR is a female-initiated option to reduce the risk of HIV infection. To properly use the ring, it must be worn inside the vagina for a period of 28 days, after which it should be replaced by a new ring. The ring is made of silicone and is easy to bend and insert. The ring works by releasing the antiretroviral drug dapivirine from the ring into the vagina slowly over 28 days.
Two Phase III randomized controlled trials found that using the DPV-VR reduced the risk of HIV infection in women and long-term use was well-tolerated. The Ring Study demonstrated an HIV reduction of 35% among women using DPV-VR, and the ASPIRE study a 27% reduction in risk.
Results from the open-label extension studies of the trials showed increases in ring use and modeling data suggest greater risk reduction — by over 50% across both studies — compared to the Phase III trials. Secondary analyses of the trial data also suggest higher risk reduction among women who consistently used the DPV-VR.
The DPV-VR is intended to reduce the risk of acquiring HIV during vaginal sex for women who are at substantial HIV risk as a complementary prevention approach in addition to other safer sex practices. It can be offered alongside oral PrEP as a choice for women who do not want or are unable to take a daily oral tablet. While contraceptive vaginal rings have been available for several years, the DPV-VR is the first vaginal HIV prevention product. Research is under way to develop a vaginal ring that includes both contraception and HIV prevention.
Since November 2020, the DPV-VR has been included on the WHO’s prequalification list of medicines. This followed the positive scientific opinion from the European Medicines Agency (EMA) under Article 58 on the use of the DPV-VR for HIV prevention, which was granted in July 2020.
At a recent WHO Guideline Development Group meeting, the Group formulated a conditional recommendation supporting offer of the DPV-VR. The Group assessed that the benefits of the DPV-VR outweigh the harms based on a systematic review and meta-analysis of the scientific evidence presented to them. This evidence included the cost–effectiveness of the dapivirine vaginal ring, acceptability, demonstrated feasibility, and the potential to increase equity as an additional prevention choice, noting some variability in effectiveness in younger age groups and limited data regarding use among pregnant and breastfeeding women.
The Guideline Development Group outlined implementation considerations and research gaps to be considered in rollout of this product. These included addressing the provision of the DPV-VR as part of comprehensive services; ensuring women are offered full information in order to make an informed choice about the benefits and potential risks when considering to use the ring; adolescent girls and young women may need more support during initiation and for continuation; acceptability among women from key population groups; additional adherence support and demand creation; training and support for providers to understand and be able to offer this new product; further information on safety in pregnancy and breastfeeding and cost-effectiveness.
WHO stresses that when providing HIV prevention services for women it is important to provide these alongside other services including the offer of other HIV prevention choices, STI diagnosis and treatment, the offer of voluntary partner services, HIV testing and links to antiretroviral therapy for all women who test positive, and a range of contraception options. Services must also be provided for women who experience intimate partner violence and health care workers need training to provide services that are respectful and inclusive of women in all their diversity.
[1] Substantial risk of HIV infection is defined as HIV incidence greater than 3 per 100 person–years.