title: Post-use assay of vaginal rings (VRs) as a potential measure of clinical trial adherence.
abstract: Adherence measurement for microbicide use within the clinical trial setting remains a challenge for the HIV prevention field. This paper describes an assay method used for determining residual dapivirine levels in post-use vaginal rings from clinical trials conducted with the Dapivirine Vaginal Matrix Ring-004 developed by the International Partnership for Microbicides to prevent male to female HIV transmission. Post-use assay results from three Ring-004 clinical trials showed that of the 25mg drug load, approximately 4mg of dapivirine is released from the matrix ring over a 28-day use period. Data obtained by both in vitro and in vivo studies indicate that dapivirine is released according to a diffusion mechanism, as determined by conformance of both data sets to the Higuchi equation. This, coupled with the low variability associated with batch production over two manufacturing sites and 20 batches of material, provides evidence that post-use ring analysis can contribute to the assessment of adherence to ring use. Limitations of this method include the potential of intra-participant and inter-participant variability and uncertainty associated with measuring the low amount of dapivirine actually released relative to the drug load. Therefore, residual drug levels should not serve as the only direct measurement for microbicide adherence in vaginal ring clinical trials but should preferably be used as part of a multi-pronged approach towards understanding and assessing adherence to vaginal ring use.
authors.affiliation: International Partnership for Microbicides, 8401 Colesville Road, Suite 200, Silver Spring 20910, MD, USA. Electronic address: pspence@ipmglobal.org.
authors.forename: Patrick
authors.initials: P
authors.lastname: Spence
authors.affiliation: International Partnership for Microbicides, 63 Main Road, Paarl 7645, South Africa.
authors.forename: Annalene
authors.initials: A
authors.lastname: Nel
authors.affiliation: International Partnership for Microbicides, 63 Main Road, Paarl 7645, South Africa.
authors.forename: Neliëtte
authors.initials: N
authors.lastname: van Niekerk
authors.affiliation: International Partnership for Microbicides, 8401 Colesville Road, Suite 200, Silver Spring 20910, MD, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Derrick
authors.affiliation: Genentech USA, Inc., 1 DNA Way, South San Francisco 94080-4990, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Wilder
authors.affiliation: International Partnership for Microbicides, 8401 Colesville Road, Suite 200, Silver Spring 20910, MD, USA.
authors.forename: Bríd
authors.initials: B
authors.lastname: Devlin
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D004333:Drug Administration Routes; D005260:Female; D019983:Guideline Adherence; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D011743:Pyrimidines / Q000008:administration & dosage*; D014621:Vagina
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines; C481671:Dapivirine
keywords: Adherence model; Dapivirine vaginal ring; Higuchi model; In vitro drug release; In vivo drug release; Post-use assay