February 22, 2016
ASPIRE (“A Study to Prevent Infection with a Ring for Extended Use”) was a large, multinational Phase 3 clinical trial designed to test the effectiveness and extended safety of a drug-infused vaginal ring for preventing HIV infection in women. Also known as MTN-020, the trial was part of ongoing research to develop a safe, effective and desirable microbicide for women.
For more information about the study results, please see the answer to question 10.
A microbicide is a form of HIV prevention applied topically inside the vagina or rectum. Vaginal microbicides have been formulated as a ring, gel, film or suppository. No microbicide has been approved for use outside of research studies.
The ASPIRE study team enrolled 2,629 HIV-uninfected women ages 18 to 45 who were sexually active but not pregnant and were at high risk for HIV infection.
The ASPIRE study took place at 15 sites in Malawi, South Africa, Uganda and Zimbabwe.
The ASPIRE study began in July 2012 and data collection ended in September 2015. The study results were reported in February 2016 at the Conference on Retroviruses and Opportunistic Infections (CROI) and published online on Feb. 22 in the New England Journal of Medicine.
Protocol chair Jared Baeten, M.D., Ph.D., professor of global health, medicine and epidemiology at the University of Washington in Seattle, and protocol co-chair Thesla Palanee-Phillips, Ph.D., director of network trials and research center programs at the Wits Reproductive Health and HIV Institute in Johannesburg, South Africa, led the study.
All study participants received a package of HIV prevention services at each study visit, including HIV risk-reduction counseling, partner HIV testing, treatment of sexually transmitted infections in participants and their partners, and free condoms. Also during study visits, the women received HIV tests, pregnancy tests and a new silicone ring. Women who became HIV-infected during the study were counseled to discontinue using the vaginal ring and were referred to local medical care and support services.
The dapivirine ring reduced the risk of acquiring HIV by 27 percent among all women enrolled in the trial. When the scientists excluded data from two sites where it was apparent early on that many women were not returning for study visits or using the ring consistently, the ring reduced the risk of HIV infection by 37 percent. Both of these findings were statistically significant.
Investigators also found that the dapivirine ring reduced the risk of HIV infection by 61 percent in women ages 25 and older but provided no statistically significant protection in women younger than 25 years. These younger women appeared to use the ring less consistently than other participants, based on the amount of dapivirine measured in volunteers’ blood during study visits.
To explore this age-related effect further, investigators performed analyses that were not originally planned and found that the ring reduced the risk of HIV infection by 56 percent in women older than 21 years, but provided no protection for women ages 18 to 21 years.
Finally, the rate of adverse medical events was similar among women who received the dapivirine ring compared to those who received the placebo ring, as was the frequency of antiretroviral resistance in women who acquired HIV.
Taken together, these results indicate that the dapivirine vaginal ring safely conferred partial protection from HIV in women in sub-Saharan Africa.
These results were reported in February 2016 at the Conference on Retroviruses and Opportunistic Infections (CROI) and published online on Feb. 22 in the New England Journal of Medicine.
The ASPIRE study is important because women need a discreet, long-acting HIV prevention method that they control and want to use. This would be particularly helpful in situations where it is difficult or impossible for women to refuse sex or to negotiate male condom use with their sexual partners. Women make up more than half of all people worldwide living with HIV, and in sub-Saharan Africa, women represent nearly 60 percent of all people living with the virus. In most cases, women become infected with HIV through sex with an infected male partner. Finding effective HIV prevention tools for adolescent girls and young women in particular is critical, as one in four new HIV infections in sub-Saharan Africa occur in this group.
The safety of study participants was evaluated at multiple levels beginning with the clinical staff at each clinical research site. Clinical research teams performed thorough checks on the health and safety of participants during each study visit. Safety also was monitored by a team at the MTN statistical and data management center, which assessed incoming reports of adverse events daily, as well as by a protocol safety review team that provided monthly oversight.
In addition, an independent Data and Safety Monitoring Board (DSMB) carefully monitored participants’ safety. A DSMB is an independent group composed of clinical research experts, statisticians, ethicists and community representatives that meets periodically during a study to review safety and efficacy data as it is gathered. A statistician who is not part of the study team presents interim data to the DSMB. Because the study team is blinded to interim study data, they are excluded from portions of meetings when data are presented. The DSMB alerts the study team if anything appears to compromise the safety of study participants, if there is compelling evidence that the study intervention is effective, or if it becomes clear that the study cannot answer one of the questions it was designed to address.
The ASPIRE study and The Ring Study are both Phase 3 clinical trials designed to test whether a silicone ring that continuously releases the experimental antiretroviral drug dapivirine in the vagina can safely and effectively prevent HIV infection. Both studies have tested the same microbicide ring developed by IPM, and both have taken place in sub-Saharan Africa. Together, the two studies enrolled more than 4,500 women.
The Ring Study investigators found an overall effectiveness of 31 percent, with a slightly greater reduction in risk of HIV infection among women older than 21 years. These results were also reported at CROI in 2016.
IPM is conducting The Ring Study, which began in 2012 and is expected to end in 2016. The study is being funded by the Bill & Melinda Gates Foundation, the U.S. President’s Emergency Plan for AIDS Relief, the U.S. Agency for International Development, and several European governments and organizations. For more information about The Ring Study, please visit the International Partnership for Microbicides website.
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Last Updated February 19, 2016
Last Reviewed February 19, 2016