Updated at 1758 EAT on 29th March 2022.
In a decision widely welcomed by civil society organisations, the South African Health Products Regulatory Authority (SAHPRA) recently approved the use of the monthly dapivirine vaginal ring for women 18 years and older to reduce the risk of HIV infection.
South Africa is one of the first countries on the continent to approve the ring, which is already recommended as an additional HIV prevention option by the World Health Organization. Other proven HIV prevention methods include the use of male and female condoms, HIV prevention pills, voluntary medical male circumcision, and a monthly HIV prevention injection (called long-acting cabotegravir or CAB LA).
The dapivirine ring is only the second form of HIV pre-exposure prophylaxis (PrEP) to be approved in South Africa. PrEP involves taking antiretrovirals to prevent HIV infection. In 2015, SAHPRA approved the combination of the antiretrovirals tenofovir and emtricitabine as oral PrEP. CAB LA is currently under consideration with SAHPRA and will probably become the third PrEP product registered in South Africa later this year.
What is the dapivirine ring?
Dapivirine is an antiretroviral drug that belongs to a class of medicines known as non-nucleoside reverse transcriptase inhibitors or NNRTIs. NNRTIs work against HIV by blocking its ability to make copies of itself once inside a healthy cell.
The ring is made of flexible silicone loaded with 25mg of dapivirine. The ring provides sustained release of the drug inside the vagina over the course of a month with low exposure elsewhere in the body, which could help minimise side effects and reduce the risk of developing HIV resistance.
Professor Thesla Palanee-Phillips of Wits RHI says it’s advised that the ring is in place for at least 24 hours to allow sufficient drug release to happen. It is, however, essential to note that the ring should be kept in place and worn continuously for a month at a time to ensure that the highest level of risk reduction is achieved through the sustained release of the drug.
She says the ring should not be removed to be cleaned or washed, nor does it need to be removed during the menstrual cycle. “We recommend it is inserted and left in place for the month whereafter it can be replaced with a new ring,” she says.
How effective is the ring?
Though the evidence is compelling that the dapivirine ring is effective, there is some uncertainty over just how effective it is. Two phase III trials first reported in 2016 found the ring to reduce HIV incidence by 27% (ASPIRE trial) and 30.7% (the ring trial) compared to placebo. In both studies, efficacy only just reached the threshold for statistical significance. Efficacy was found to be higher and lower in some sub-groups – an effect most likely driven by differing levels of adherence.
More recent evidence from two open-label trials (DREAM and HOPE) suggests efficacy in real-world use is better than in the two phase III trials, most likely due to better adherence. Even so, efficacy appears to be lower than that for oral PrEP.
“We can’t assume 100% efficacy. That’s tough for any prevention measure. But the data shows that the efficacy was better when the ring was used more than (in trials), so the dose-response curve is reassuring,” says Professor Linda-Gail Bekker of the Desmond Tutu HIV Foundation. According to Bekker, findings from randomised controlled trials of oral PrEP trials in women in Africa, such as VOICE and FEMPREP, were even more disappointing.
“The best results in randomised controlled trials have been with CAB LA (the injection) since the adherence issues are reduced when a third party administers a prevention measure. With that said, the proof is in the real world effectiveness and we have seen oral PrEP do a lot better in reality compared with the randomised controlled trials. We hope the same will happen with the vaginal ring. The open-label study indicated it should,” she says.