July 24, 2019
by NIH / National Institute of Allergy and Infectious Diseases
A woman holds the dapivirine vaginal ring. Credit: Andrew Loxley, International Microbicides Association
According to a statistical model, an open-label study of women in southern and eastern Africa estimated that a vaginal ring inserted once a month that slowly releases an antiviral drug reduces the risk of HIV by 39%. Furthermore, the study found that participants appeared to use the ring more frequently in the open-label study than in a previous clinical trial. These and other results from the HIV Open Label Extension (HOPE) study were presented today at the 10th IAS Conference on HIV Science (IAS 2019) in Mexico City.
In 2017 alone, nearly 870,000 women and girls contracted HIV, according to UNAIDS. Currently available HIV prevention methods for women are limited, and many women cannot negotiate condom use with their sexual partners. The vaginal ring tested in the HOPE study, which continuously releases the anti-HIV drug dapivirine, was designed to be a discreet, long-term HIV prevention option for women. The user replaces the ring herself once every four weeks. The dapivirine vaginal ring is currently under regulatory review by the European Medicines Agency.
“Women need HIV prevention tool options that fit their needs and that they can initiate,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health and the primary funder of the HOPE study. “With valuable contributions from thousands of study participants, the HOPE study has estimated the effectiveness of the dapivirine ring and examined its appeal to users. Additional efforts to develop HIV prevention options continue with the hope that one day women will have a range of HIV prevention products to make an informed choice.”
The Phase 3b HOPE study was a follow-up to the NIH-funded ASPIRE clinical trial. ASPIRE and a clinical trial called The Ring Study demonstrated in 2016 that the dapivirine ring reduced the risk of HIV infection by approximately 30% in women aged 18 to 45 and was well-tolerated. The goals of the HOPE study were to collect additional data on the safety of the dapivirine ring and new data on whether and how women knew they were using it, given that previous trials had shown it to be moderately effective.
The HOPE study began in 2016 and included 1,456 participants from the ASPIRE study at 14 sites in Malawi, South Africa, Uganda, and Zimbabwe. The women were sexually active, HIV-negative, and between 20 and 49 years of age.
While participants in the ASPIRE study did not know until the end of the trial whether they had received the dapivirine ring or a placebo ring, all women who enrolled in the HOPE study were offered the dapivirine ring. For the first three months in the HOPE study, participants attended monthly study visits where they could receive a new ring. Thereafter, they attended quarterly visits where they could receive three new rings—a schedule that more closely resembled how the ring might be distributed in a real-world setting.
Women could remain in the study regardless of whether they chose to accept the ring. Approximately 92% of participants accepted the ring at enrollment, and 90% accepted it at their first study visit. The proportion of participants who accepted the ring decreased at each subsequent visit, falling to 79% at the 9-month study visit.
Although it was not possible to precisely quantify the amount of time participants used the dapivirine ring in the HOPE or ASPIRE studies, adherence appeared to be higher in HOPE than in ASPIRE. Adherence was assessed by measuring the amount of dapivirine remaining in returned rings, as the level of dapivirine decreases with use. The amount of dapivirine remaining in 90% of the rings returned by HOPE participants indicated that those rings had been used for at least part of the previous month. In contrast, the amount of dapivirine remaining in 77% of the rings returned by ASPIRE participants indicated that those rings had been used for at least part of the previous month. The ring is designed to be worn continuously throughout the month to provide effective protection.
Participants in the HOPE study became infected with HIV at a rate of 2.7% during the one-year follow-up. Because the study lacked a concurrent control group receiving a placebo ring, researchers used a mathematical approach based on the ASPIRE placebo group to estimate what the incidence of HIV in HOPE would have been if the women had not had access to the dapivirine ring. In this modeling exercise, the average incidence of HIV was 4.4% during the one-year follow-up. Based on these incidence rates, researchers estimate that the ring reduced the risk of HIV infection by 39% in the HOPE study. The study was not designed to determine the effectiveness of the ring.
Comparing the HOPE study population with the ASPIRE placebo group has important limitations. These include the fact that all participants in the HOPE study had previously completed the ASPIRE trial without contracting HIV. This suggests that some aspect of their behavior other than dapivirine ring use, or the characteristics of their sexual networks, may have contributed to their protection against the virus.
Also known as MTN-025, the HOPE study was implemented by the Microbicide Trials Network (MTN), funded by the NIH. The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, both part of the NIH, co-fund the MTN with the NIAID.
The HOPE study was sponsored by the non-profit organization International Partnership for Microbicides (IPM), which developed the dapivirine ring and provided it for the study. IPM conducted its own open-label study of the dapivirine ring called DREAM, which reported its final results on June 13 at the South African AIDS Conference in Durban.
The HOPE study was led by Jared Baeten, MD, Ph.D., professor of global health, medicine and epidemiology at the University of Washington in Seattle; Thesla Palanee-Phillips, Ph.D., M.Sc., director of research center and network trials programs at the Wits Institute for Reproductive Health and HIV in Johannesburg, South Africa; and Nyaradzo M. Mgodi, MBCh.B., M.Med., clinical pathologist and clinical research site leader at the Clinical Trials Research Program of the College of Health Sciences at the University of Zimbabwe in Harare.
“Women urgently need more HIV prevention options that fit into their lives,” said Dr. Baeten. “The results published today show that some women may want to use the monthly dapivirine vaginal ring, if available, to protect themselves against HIV.”
Pre-exposure prophylaxis, or PrEP, provides high levels of protection against HIV in both women and men. PrEP involves taking daily oral tablets of the drug Truvada, which reduces the risk of HIV infection by more than 95 percent in high-risk individuals when taken as prescribed. However, taking a daily pill can present challenges for some populations.
In addition to the vaginal ring, the NIH is investigating other long-acting forms of HIV prevention that may be safe and effective options for both women and men.
Provided by NIH / National Institute of Allergy and Infectious Diseases
From: https://medicalxpress.com/news/2019-07-women-vaginal-hiv-open-label.html