Factors associated with tenofovir diphosphate concentrations in dried blood spots in persons living with HIV

Abstract

Objectives To determine factors associated with interindividual variability in tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBSs) among persons living with HIV (PLWH). Methods PLWH who were at least 18 years old and taking tenofovir disoproxil fumarate-containing ART were prospectively recruited and enrolled from a clinical cohort and followed longitudinally (up to three visits over 48 weeks). With log-transformed TFV-DP concentrations in DBSs as the outcome, mixed-model regression analyses were used to assess associations between self-reported 3 month ART adherence, race and other clinical covariates (gender, age, BMI, CD4+ T cell count, estimated glomerular filtration rate, haematocrit, duration on current ART and anchor drug class) on TFV-DP in DBSs. Results Five hundred and twenty-seven participants (1150 person-visits) were analysed. Adjusting for race and other clinical covariates, every 10% increase in self-reported 3 month ART adherence was associated with an average TFV-DP concentration increase in DBSs of 28% (95% CI: 24%–32%; P < 0.0001). In the same model, female participants had 20% (95% CI: 3%–40%; P = 0.02) higher TFV-DP concentrations in DBSs, compared with male participants, and every 1 kg/m2 increase in BMI was associated with a decrease in TFV-DP concentration in DBSs by 2% (95% CI: −3% to −1%; P < 0.0001). Conclusions Individual patient characteristics were predictive of TFV-DP concentration in DBSs in PLWH receiving tenofovir disoproxil fumarate-based ART. Future research to incorporate these predictors into the interpretation of this ART adherence biomarker, and to establish whether these associations extend to PLWH taking tenofovir alafenamide-containing ART, is needed.

Pilot Evaluation of an Enzymatic Assay for Rapid Measurement of Antiretroviral Drug Concentrations

“…We will also investigate how factors like BMI, sex, and drug-drug interactions in uence intracellular TFV-DP drug levels. (32) We will validate the RESTRICT assay to meet established Clinical Laboratory Improvement Amendments criteria to enable reporting of results to clients. The RESTRICT assay could be used to evaluate the role of adherence in treatment failure and emergence of drug resistance among people living with HIV.…”

Associations Between Tenofovir Diphosphate in Dried Blood Spots, Impaired Physical Function, and Fracture Risk

“…We have previously shown (1) the impact of fat mass or BMI on physical function performance [ 31 , 32 ] and (2) a strong association between BMI and TFV-DP in DBS among a large clinical cohort of PWH [ 33 , 34 ]. Here, higher TFV-DP in DBS were associated with slower chair rise time, slower time to complete a 400-meter walk, and SPPB impairment.…”

Higher medication complexity in persons with HIV is associated with lower tenofovir diphosphate in dried blood spots

“…As noted, HIV VL and DBS were collected simultaneously throughout the study. Dried blood spots (DBS) were assayed using a longitudinal case–control extension strategy, where PWH who had a detectable HIV VL (>20 copies/mL) at any of their study visits were considered to be cases, and those with viral suppression at all study visits where considered controls, as previously reported in this cohort 1,8,9 …”

“…Among the available measures of ART adherence are self‐report, pharmacy refills, electronic monitoring, directly observed therapy (DOT), electronic pill boxes, and pharmacologic biomarkers, such as drug concentrations in urine, hair, and dried blood spots (DBS) 7 . Previous research on tenofovir diphosphate (TFV‐DP) in DBS, a measure of cumulative ART adherence and exposure in PWH taking tenofovir‐based regimens, has demonstrated that this adherence biomarker is strongly associated with viral suppression, is predictive of future viremia, and is influenced by several biological, demographic, and social factors 1,8–11 . Despite the potential simplicity of ART, PWH may be taking numerous additional medications, including over‐the‐counter (OTC) agents, which can increase the burden on medication adherence.…”