Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV

Abstract

Background: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is associated with viral suppression in persons living with HIV (PLWH) taking tenofovir disoproxil fumarate (TDF). However, its value as a predictor of future viremia remained unknown.

Methods: Blood for plasma viral load (VL) and TFV-DP in DBS were collected (up to 3 visits within 48 weeks) in PLWH on TDF. TFV-DP cut points were selected using logistic prediction models maximizing the area under the receiver operation characteristic curve, and estimated adjusted odds ratio (aOR) of future viremia (≥20 copies/mL) were compared to the highest TFV-DP category.

Results: Among all 451 participants in the analysis, aOR of future viremia for participants with TFV-DP <800 and 800 to <1650 fmol/punch were 4.7 (95% CI, 2.6-8.7; P < .0001) and 2.1 (95% CI, 1.3-3.3; P = .002) versus ≥1650 fmol/punch, respectively. These remained significant for participants who were virologically suppressed at the time of the study visit (4.2; 95% CI, 1.5-12.0; P = .007 and 2.2; 95% CI, 1.2-4.0; P = .01).

Conclusions: TFV-DP in DBS predicts future viremia in PLWH on TDF, even in those who are virologically suppressed. This highlights the utility of this biomarker to inform about adherence beyond VL. Clinical Trials Registration. NCT02012621.

Keywords: adherence; antiretroviral therapy; dried blood spots; pharmacokinetics; predictive value; tenofovir diphosphate.

Figure 1.

Trajectory of TFV-DP in DBS in participants in whom drug concentrations were available for all 3 study visits (N = 213) according to drug concentration category. Colors represent TFV-DP categories with green indicating higher concentrations (≥1650 fmol/punch), yellow medium concentrations (800 to <1650 fmol/punch), and red low concentrations (BLQ to <800 fmol/punch) of TFV-DP. Each line within each category represents 1 participant. Individuals with the same progression of TFV-DP over time are grouped together forming thicker color bands. At visit 2, n = 115, n = 74, and n = 24 participants were included in the high, medium, and low concentrations, respectively. Abbreviations: BLQ, below limit of quantification; DBS, dried blood spots; TFV-DP, tenofovir diphosphate.