Tenofovir-Diphosphate in Dried Blood Spots vs Tenofovir in Urine/Plasma for Oral Preexposure Prophylaxis Adherence Monitoring. (10th August 2022)

• Record Type: Journal Article
• Authors: Niu, Xin; Kubiak, Rachel W; Siriprakaisil, Oraphan; Klinbuyaem, Virat; Sukrakanchana, Pra ornsuda; Cressey, Ratchada; Okochi, Hideaki; Gandhi, Monica; Cressey, Tim R; Drain, Paul K
• Is Part Of: Open forum infectious diseases. Volume 9:Number 8(2022)
• Publication Date: 2022-08-10
• Subjects: tenofovir-diphosphate -- HIV -- adherence -- preexposure prophylaxis -- tenofovir; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac405
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Tenofovir-diphosphate (TFV-DP) measured in dried blood spots (DBS) and tenofovir (TFV) measured in urine/plasma have been used to measure TFV-based oral pre-exposure prophylaxis (PrEP) adherence. However, there are limited data comparing these 3 metrics and their appropriate use for PrEP adherence monitoring. Methods: We collected DBS, urine, and plasma samples from HIV-negative adults randomized to a low (2 doses/week), moderate (4 doses/week), or perfect (7 doses/week) adherence group (via directly observed therapy) of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for 6 weeks, followed by a 4-week washout phase. Drug concentrations were measured using liquid chromatography tandem mass spectrometry. Linear mixed-effects modeling was used to examine associations between drug concentrations and dosing time. Results: Among 28 participants, the median age was 33 years, and 12 (43%) were female. At steady state, 25th percentile TFV-DP concentrations were 466, 779, and 1375 fmol/3 mm punch in the low, moderate, and perfect adherence group, respectively. Correlation was stronger between quantifiable TFV-DP and plasma TFV ( r = 0.65; P < .01) than between TFV-DP and urine TFV ( r = 0.50; P < .01). Among all participants, each additional week of cumulative dosing on average led to a mean increase of 158 fmol/3 mm punch ( P < .001) in TFV-DP during the dosing phase. Each additional day after the last dose was associated with 43 fmol/3 mm punch lower TFV-DP ( P = .07). Conclusions: TFV-DP levels in DBS provide valuable insight into both dosing recency and cumulative doses from variable adherence patterns. Our observed benchmark TFV-DP concentrations were slightly higher than prior predicted estimates based on convenience samples.