Disclosure of pharmacokinetic drug results to understand nonadherence

Abstract

Objectives In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, ≥50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic (PK) results, explored adherence challenges during VOICE. Methods We systematically recruited participants with PK data (median 6 plasma samples), categorized as low (0%, N=79), inconsistent (1%-74%, N=28), or high (≥75%; N=20) based on frequency of tenofovir detection. Following disclosure of PK results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded, and thematically analyzed. Results We interviewed 127 participants from South Africa, Uganda, and Zimbabwe. The most common reactions to PK results included surprise (41%; low PK), acceptance (39%; inconsistent PK), and happiness (65%; high PK). Based on participants’ explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen), and adherence. Fear of product side effects/harm was a frequent concern, fueled by stories shared among participants. Although women with high PK levels reported similar concerns, several described strategies to overcome challenges. Women at all PK levels suggested real-time drug monitoring and feedback to improve adherence and reporting. Conclusions Retrospective provision of PK results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials.

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

“…Of importance in this study was that only 1% of participants were concerned about providing a sample that could reveal their adherence level and other studies have suggested that provision of drug levels could improve subsequent drug-taking. [35, 36] However, both DBS and hair require expensive liquid chromatography/ tandem mass spectrometry equipment for analyses and are performed in high-level research laboratories in the U.S. Lower-cost methods that can be applied to real-world implementation in the field and to assess drug taking using point-of-care technology will be the next advances in the field.…”

Divergent adherence estimates with pharmacokinetic and behavioural measures in the MTN‐003 (VOICE) study

“…Indeed, findings from two qualitative ancillary studies indicate that participants were motivated to enrol and stay in VOICE for the quality health care, regular HIV testing, and other benefits, but were fearful of using the investigational products, which contained ARVs, so that they likely concealed their poor adherence to remain in the trial [40,42,43]. This occurred despite implementing a participant-centred, need-based, non-judgmental approach to product adherence counselling during VOICE, where we were striving for accuracy and honesty [44].…”

“…Similarly, in Fem-PrEP, women feared being terminated from the study if they reported their actual behaviour [36]. Given limited or no alternatives for accessing quality health services outside the trial setting, participants may be encouraged to over-report if there is mistrust about the research, no objective means of ascertaining product use and if they perceive negative consequences to telling the truth [24,36,40,42,45]. …”

“…In Fem-PrEP feeling at risk of getting HIV in the next 4 weeks was not associated with adherence; however, it was marginally associated with over-reporting pill use [48,49]. Qualitative data suggested that HIV risk perception was an important motivator for joining VOICE to access regular testing and health checks, but not necessarily to use the products, hence those motivated to stay in the study may have had many reasons to simply appear adherent [42]. For the vaginal gel group, those who reported being “somewhat” worried about HIV were less likely to over-report.…”

Collateral benefits: how the practical application of Good Participatory Practice can strengthen HIV research in sub‐Saharan Africa

“…In some cases, blame for these outcomes was placed on the women study participants–accused of not adhering to the study products and then lying about this to trial staff 20, 21. Subsequent inquiry into these indications of sub‐optimal adherence seemed to confirm that indeed, there had been major discrepancies between self‐reported product use and pharmacokinetic measures of adherence 22. Nevertheless, the allegations that participants had lied brought to the surface deep‐rooted tensions associated with historic power disparities between marginalized, working class populations and an educated elite.…”