Application of a composite measure of product adherence, protocol compliance, and semen exposure to a phase III microbicide HIV prevention trial

Terry A Jacot,Andrea R Thurman,Oluwatosin E Adedipe,Sinead Delany-Moretlwe,Jill L Schwartz,Susan Ju,Tina Cunningham,Gustavo F Doncel,Meredith R Clark,Susan Godbout

doi:10.1186/s41231-021-00100-6

Terry A Jacot, Andrea R Thurman + Show 8 more

Open Access

https://doi.org/10.1186/s41231-021-00100-6

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Abstract

BackgroundStrict adherence to antiretroviral-based microbicide use is important for effective HIV prevention. We previously developed a composite measure of product adherence, protocol compliance, and semen exposure for determining vaginal use of tenofovir (TFV) 1% gel applicators through biomarkers and residual drug analyses. In this study, we tested the ability of the composite measure in vaginally used TFV gel applicators from a Phase III HIV prevention clinical trial.MethodsUsed vaginal gel applicators from the FACTS 001 study were swabbed for detection of vaginal bacterial markers (vaginal insertion), semen DNA markers (semen exposure), and residual TFV gel (product use).ResultsOf 1,098 evaluable TFV and placebo applicators, 80% had detectable vaginal insertion biomarkers and 52% had semen biomarkers. Ninety-nine percent of vaginally inserted applicators TFV applicators had detectable residual TFV as measured by liquid chromatography with tandem mass spectroscopy (LC–MS/MS). Residual TFV levels were also successfully detected using Fourier Transform Infrared (FTIR)-based spectroscopy.ConclusionsVaginal insertion and semen exposure biomarkers were detectable on used TFV 1% gel applicators. Residual TFV on these gel applicators was detectable by LC–MS/MS and FTIR-based spectroscopy, which has potential to be a more convenient and quicker method for detecting drug use. With continual improvements, this composite measure of product adherence, protocol compliance, and semen exposure has potential to assess use of not only TFV gel but also other topical microbicides or products.

Highlights

Strict adherence to antiretroviral-based microbicide use is important for effective HIV prevention
Since subjectivity of the “readers” could still affect adherence assessments by these methods, we developed a more objective composite measure of product adherence, protocol compliance, and semen exposure from a singleuse vaginal gel applicator (Fig. 1), [10]
We previously reported the use of Fourier Transform Infrared (FTIR)-based spectroscopy to detect TFV, which would be a faster approach than LC–MS/MS in detecting product for adherence determination in a clinic [13]

Summary

Introduction

Strict adherence to antiretroviral-based microbicide use is important for effective HIV prevention. We previously developed a composite measure of product adherence, protocol compliance, and semen exposure for determining vaginal use of tenofovir (TFV) 1% gel applicators through biomarkers and residual drug analyses. We tested the ability of the composite measure in vaginally used TFV gel applicators from a Phase III HIV preven‐ tion clinical trial. Antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is one option for effective HIV prevention. Tenofovir (TFV) 1% vaginal gel was tested for effectiveness in preventing HIV acquisition using a single application daily dose or a peri-coital “BAT24” regimen. Using the BAT24 regimen, the CAPRISA 004 study in South Africa was the first successful clinical trial that showed a statistically significant reduction of HIV acquisition [2]. Consistent use at the time of potential exposure was an important factor influencing effectiveness of the gel

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