Rapid measures of user's adherence to vaginal drug products using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and multivariate discriminant techniques

PLoS One. 2018 May 25;13(5):e0197906. doi: 10.1371/journal.pone.0197906. eCollection 2018.

Abstract

Background: The topical HIV prevention (microbicides) field is in acute need of a method to rapidly and objectively measure adherence to product use in clinical trials. Infrared (IR) spectroscopy has been used in many pharmaceutical and forensic applications but has yet to be applied to adherence monitoring. In this study, we report on efforts to test the feasibility of using IR spectroscopy as a means to measure residual active or placebo vaginal product, semen exposure and vaginal insertion from a single swab.

Methods: A portable IR spectrometer equipped with diamond attenuated total reflectance (ATR) was used to capture spectra of unused vs. vaginally-used swabs, vaginal swabs containing semen, and vaginal swabs to which either tenofovir-containing or matching placebo products (vaginal gel or insert) were added. Spectral data obtained from swabs placed directly on the spectrometer were divided into calibration and testing sets for developing and validating discriminant models set up to provide yes/no predictions of: vaginal vs. non-vaginal use, presence vs. no presence of each test product, and presence vs. no presence of semen. Further validation of models was performed using vaginal swabs collected from a clinical study evaluating vaginally administered placebo insert formulations.

Results: For each discriminant model developed to predict vaginal vs. non-vaginal use, presence vs. no presence of each test product, and presence vs. no presence of semen, classified validation samples not included in the model development were correctly identified into their respective classes with minimal prediction error. Clinically obtained vaginal swabs collected 15-60 minutes after placebo insert use were also correctly identified, further validating the models.

Conclusion: Our findings demonstrate the proof of concept that IR spectroscopy can be a method for rapid detection and characterization of microbicide products and biological fluids present in vaginal swabs. This novel method has potential to support real-time, on-site adherence monitoring in clinical or field settings.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Intravaginal
  • Anti-Infective Agents / administration & dosage*
  • Discriminant Analysis
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Multivariate Analysis
  • Patient Compliance / statistics & numerical data*
  • Placebos
  • Semen / metabolism
  • Spectroscopy, Fourier Transform Infrared*
  • Time Factors

Substances

  • Anti-Infective Agents
  • Placebos

Grants and funding

This work was supported by United States Agency for International Development (USAID) under Cooperative Agreements (AID-OAA-A-14-00005 and AID-OAA-A-14-00010) awarded to CONRAD, www.usaid.gov; Bill & Melinda Gates Foundation, #OPP1114939 awarded to CONRAD, www.gatesfoundation.org.