EXECUTIVE SUMMARY

In hard-hit sub-Saharan Africa, where young women are disproportionately affected by HIV, new research from an open-label trial of a dapivirine vaginal ring confirms that women will use the device as prevention against HIV.

• Dapivirine, also known as TMC-120, is an anti-HIV drug that binds to and disables HIV’s reverse transcriptase enzyme, a protein needed for HIV to produce copies of itself.

• The nonprofit International Partnership for Microbicides, which developed the dapivirine ring, is seeking regulatory approval for the device.


In 2017, estimates indicated there were 37 million people living with HIV and 1.8 million new infections around the globe.1 In hard-hit sub-Saharan Africa, where young women are disproportionately affected by HIV, new research from an open-label trial of a dapivirine vaginal ring confirms that women will use the device to prevent HIV.2 The ring was estimated to reduce the risk of HIV by 39%, according to statistical modeling.

Results of the HIV Open Label Extension (HOPE) study were presented at the 10th International AIDS Society Conference on HIV Science in Mexico City. The study continued work begun by the ASPIRE clinical trial. The ASPIRE trial, along with a sister investigation called The Ring Study, demonstrated that the dapivirine ring reduced the risk of HIV infection by about 30% in women ages 18-45 years and was well-tolerated.3,4 HOPE study researchers gathered additional data on the safety of the dapivirine ring and new data on whether and how women used it, since earlier trials had shown modest effectiveness.

HOPE Shows Results

Begun in 2016, HOPE study researchers enrolled 1,456 former ASPIRE study participants at 14 sites in Malawi, South Africa, Uganda, and Zimbabwe. The women, ages 20-49 years, were sexually active and HIV-negative. Study participants received free laboratory tests, physical and pelvic exams, HIV prevention counseling, and condoms. All participants were offered the dapivirine ring. During their first three months in the trial, participants attended monthly study visits where they could receive one new ring. After the first month, women attended quarterly visits where they could receive three new rings. This schedule was designed to more closely resemble how the ring might be distributed in a real-world setting.

Participants could remain in the trial even if they did not accept the ring. Analysis indicates that 92% of women accepted the ring at enrollment, and 90% accepted it at their first study visit. The proportion of participants who accepted the ring dropped at each subsequent visit, declining to 79% at the nine-month study visit.

Since the drug level declines when the ring is worn, investigators assessed adherence by measuring how much dapivirine was left in returned rings. Results indicated that the amount of dapivirine left in 90% of the returned rings from HOPE study participants showed that the devices had been used for at least part of the prior month; in the ASPIRE trial, 77% of the returned rings indicated similar use.

“We wanted women to know that the decision was theirs to make, and theirs alone,” says Jared Baeten, MD, PhD, professor of global health, medicine, and epidemiology at the University of Washington in Seattle. “As it turns out, most participants wanted the dapivirine ring — they accepted the ring being offered. Women in HOPE also appeared to use the ring more consistently than they did in ASPIRE.”

Ring Under Review

Baeten, who presented the study findings at the IAS conference, is co-principal investigator of the National Institutes of Health-funded Microbicide Trials Network. He led the HOPE study with Thesla Palanee-Phillips, MMed Sci, PhD, MSc, of the Wits Reproductive Health and HIV Institute in South Africa, and Nyaradzo Mgodi, MBChB, MMed, of the University of Zimbabwe College of Health Sciences.

Dapivirine, also known as TMC-120, is an anti-HIV drug that binds to and disables HIV’s reverse transcriptase enzyme, a protein needed for HIV to produce copies of itself.

The nonprofit International Partnership for Microbicides, which developed the dapivirine ring, is seeking regulatory approval for the device. It is under review by the European Medicines Agency. If approved, it would allow the agency, in cooperation with the World Health Organization, to provide a scientific opinion on the ring’s use in low- and middle-income countries. The partnership also plans to submit applications to the South African Health Products Regulatory Authority and the FDA.

If approved, the ring would add another option to such women-controlled HIV prevention methods as oral pre-exposure prophylaxis. Women need choices that fit their needs and that they can initiate, noted Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which was the primary funder of the HOPE study. “With the invaluable contributions of thousands of study participants, the HOPE study has estimated the effectiveness of the dapivirine ring and examined its appeal to users,” said Fauci in a press statement. “Additional efforts to develop HIV prevention options continue in the hope that one day, women will have a range of HIV prevention products from which to make an informed choice.” (The statement can be viewed online at: https://bit.ly/2ZkSFTm.)

REFERENCES

  1. UNAIDS. Miles to go: Closing gaps, breaking barriers, righting injustices. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS (UNAIDS); 2018.
  2. Baeten J, Palanee-Phillips T, Mgodi N, et al. High adherence and sustained impact on HIV-1 incidence: Final results of an open-label extension trial of the dapivirine vaginal ring. Presented at the 10th IAS Conference on HIV Science, Mexico City, July 2019.
  3. Nel A, van Niekerk N, Kapiga S, et al; Ring Study Team. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med 2016;375:2133-2143.
  4. Baeten JM, Palanee-Phillips T, Brown ER, et al; MTN-020–ASPIRE Study Team. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med 2016;375:2121-2132.