Dapivirine-Maraviroc Ring

Fast facts

  • Acts against: HIV-1
  • Delivery method: Silicone matrix vaginal ring
  • Active ingredients: Dapivirine and maraviroc, both antiretroviral drugs
  • Length of action: One month
  • Status: Development currently suspended

Why is the dapivirine-maraviroc ring important?

Combining ARVs that use different mechanisms of action to attack HIV in a single product may offer greater protection than a single drug alone and help reduce the chance of acquiring drug-resistant HIV.

How would the dapivirine-maraviroc ring work? 

The vaginal ring is made of a flexible silicone matrix polymer and contains two ARVs: dapivirine, an NNRTI, and maraviroc, a CCR5 receptor inhibitor. Both drugs are slowly released over the course of a month.  

Women insert the ring themselves into the vagina and replace it monthly.

What is its development history? 

IPM began exploring a dapivirine-maraviroc ring in 2009, developing multiple prototypes alone and in collaboration with Queens University Belfast. After extensive preclinical testing to identify a polymer and determine drug levels for target release rates, IPM selected a one-month silicone matrix ring formulation.

What is its clinical history?

IPM partnered with the Microbicide Trials Network in 2011 to conduct MTN-013/IPM 026, a Phase I trial of the dapivirine-maraviroc ring — marking the first time a combination microbicide reached clinical trials, and the first time maraviroc was clinically studied for HIV prevention. 

The trial assessed the pharmacokinetics and safety of the dapivirine-maraviroc ring, a dapivirine-only ring, a maraviroc-only ring and a placebo ring in 48 healthy, HIV-negative women in the United States. 

What are the results so far? 

In 2014, the Phase I trial found the dapivirine-maraviroc ring to be well-tolerated and acceptable to women. Dapivirine was detectable in plasma, vaginal fluid and cervical tissue, with low systemic absorption, while maraviroc was detectable in vaginal fluid but showed low levels in cervical tissue.

What are the next steps for the dapivirine-maraviroc ring?

IPM is partnering with the Oak Crest Institute of Science to reformulate the ring to increase the release of maraviroc. The reformulated ring under investigation utilizes Oak Crest’s controlled-release ring delivery system, which uses embedded ARV-loaded pods to release the drugs.

While these prototype rings could inform future combination ARV product development, findings from IPM’s research on maraviroc suggest that its efficacy as a microbicide may be limited. IPM has suspended development of maraviroc, in keeping with IPM’s prioritization protocol to put resources behind the ARVs that show the highest likelihood of success as vaginal microbicides. IPM will reassess maraviroc’s potential as a microbicide when additional data from ongoing clinical trials of maraviroc are available.

Who is IPM currently partnering with to develop and test the ring?

  • ARV licenses: Janssen Sciences Ireland UC for dapivirine and ViiV Healthcare for maraviroc
  • Development: Oak Crest Institute of Science
  • Clinical trials: Microbicide Trials Network

Where can I learn more?