Mutations associated with resistance to dapivirine vaginal ring: reported in 7/38 women seroconverting in the open-label HOPE study

1 October 2023. Related: HIV prevention and transmission.

Kirk Taylor, HIV i-Base

A brief report in JAIDS highlights mutations associated with dapivirine (DPV) resistance in seven women who seroconverted during the open-label MTN-025/HOPE trial. [1]

These mutations decreased susceptibility to DPV by three-fold for 6/7 women.  

During the open-label study, 38/1456 participants seroconverted and 7/38 women (18%) developed the following DPV-associated resistance mutations: A98G, K103N, V106M, E138A and V179D.

DPV resistance did not increase in people who continued to use DPV rings for more than three months after their HIV diagnosis.

Two DPV-associated mutations (K103N and V179I) were also reported in one woman who did not use the DPV ring, reducing DPV-susceptibility by 9-fold.

As these are either commonly associated with first-line NNRTIs (efavirenz and nevirapine) this was reported as likely transmission of drug-resistant HIV, rather than recently having developed in relation to DPV use for prevention. [2]

It is unclear how many of the other cases might also have been due to transmitted drug resistance.

comment

These are important findings, given the low overall efficacy of DPV rings, usually due to low adherence.

Retention after four months dropped to only around 60% and was similar to oral PrEP, in a study from Zimbabwe, reported at IAS 2023. [3]

References

1. Parikh UM et al. HIV drug resistance assessment among women who seroconverted during the MTN-025/HOPE open-label extension dapivirine vaginal ring trial. JAIDS. DOI: 10.97/QAI.0000000000003308 (20 September 2023).
   https://journals.lww.com/jaids/abstract/9900/hiv_drug_resistance_assessment_among_women_who.299.aspx
2. Stanford drug resistance database. NNRTI Resistance Notes
   https://hivdb.stanford.edu/dr-summary/resistance-notes/NNRTI
3. Munjoma M et al. Dapivirine vaginal ring (DPV-R): An acceptable and feasible HIV prevention option. Evidence from Zimbabwe. IAS 2023, oral abstract OAD04023.
   https://programme.ias2023.org/Abstract/Abstract/?abstractid=4452

This report was first posted on 25 September 2023.