Tenofovir-Diphosphate in Dried Blood Spots vs Tenofovir in Urine/Plasma for Oral Preexposure Prophylaxis Adherence Monitoring

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.