The vaginal ring against HIV: regulatory approval for a new prevention choice for women

The European Medicines Agency (EMA) has announced a “positive benefit-risk opinion” on the use of the vaginal ring containing the anti-HIV medication dapivirine. The ring is the first HIV prevention option specifically designed for women since the female condom was approved nearly 30 years ago.

The EMA’s positive opinion should ensure that the ring, which has been in development for well over a decade and whose efficacy data was announced in 2016 in the paired RING and ASPIRE studies, should finally become available as an HIV prevention option for women in lower-income countries – primarily in Africa – by next year.

The Chief Executive Office of the International Partnership for Microbicides (IPM), Dr Zeda Rosenberg, told aidsmap.com that the EMA examined the data from the RING study under its Article 58. This provision, unique to the EMA, evaluates a drug intended for use in lower-income countries with the same rigour as a drug destined for the European market.

Glossary

European Medicines Agency (EMA)

Regulatory agency that evaluates medicines for safety and efficacy in Europe, performing a similar role to the Food and Drug Administration (FDA) in the United States. The EMA recommends to the European Commission that a medicine can be marketed in the European Union and European Economic Area.

vaginal ring

A device that is worn inside the vagina for a month at a time, which women can insert and remove themselves. A vaginal ring for HIV prevention that slowly releases the antiretroviral drug dapivirine is being developed.

oral

Refers to the mouth, for example a medicine taken by mouth.

mathematical models

A range of complex mathematical techniques which aim to simulate a sequence of likely future events, in order to estimate the impact of a health intervention or the spread of an infection.

topical

Applied directly to the affected area, as opposed to systemic. For example, a cream or lotion, applied to body surfaces such as the skin or mucous membranes inside the vagina or rectum.

 

“We’re not seeking a European market,” she told aidsmap.com, “but Article 58 enables two steps that normally happen consecutively – the scientific approval of a drug, and then the development of guidelines and pre-qualification by the World Health Organization – to happen at the same time.”

In anticipation of a licence being given to distribute the ring in at least some African countries by 2021, IPM has signed a manufacturing agreement with the Swedish firm Q Pharma to produce the rings.

With consistent use, it is estimated by IPM that the vaginal ring can stop at least 60% of HIV infections via vaginal sex; this was nearly reached in the open-label studies of the ring. As usage has grown, efficacy has now reached 65% and could be up to 90% with 100% adherence, a modelling study suggests.

Nonetheless, it is recognised that the ring’s efficacy, even with ideal use, is not as high as that of oral PrEP. Because of this, Dr Rosenberg commented, guidelines should be drawn up to place the ring in a “hierarchy” of different prevention methods.

“Many women will either decide they do not want to use oral PrEP, find it gives them side effects, or may simply find access problematic,” she said, “and experiences with contraception show some women prefer topical methods.”

Guidelines will need to be drawn up to inform women of the efficacy of methods used both singly or together, as with the ring and condom use. In addition, they will need to be informed that the ring  protects against HIV acquisition during vaginal sex, but not by other routes, notably anal sex. Future methods such as injectable PrEP can be introduced into this hierarchy as they become available.

The ring currently lasts a month and then the woman can insert a new one, but IPM is working on one that lasts three months and is also developing a ring that can be used both to prevent HIV and as a contraceptive.

“The monthly dapivirine ring provides women with the first discreet, long-acting HIV prevention choice,” Dr Sinead Delaney-Moretlwe, the South African scientist who is also chair of HPTN 084, the study of injectable PrEP for women, in a World Health Organization statement on the approval of the vaginal ring.