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

Abstract

BackgroundTenofovir 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.MethodsBlood 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.ResultsAmong 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).ConclusionsTFV-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.

Income Inequality Is Associated With Low Cumulative Antiretroviral Adherence in Persons With Human Immunodeficiency Virus

“…Log-transformed TFV-DP concentrations were analyzed using a mixed-effects model to estimate the percentage change in drug concentrations for every significant change in the SDoH. We initially evaluated a model in which each individual SDoH (ie, household income, percent living in poverty, education level and income inequality) was the primary predictor of interest, and then we evaluated a model that adjusted for potential confounders that were selected a priori, including age, gender, race, body mass index (BMI), type of ART anchor drug class (nonnucleoside-based, boosted protease inhibitor-based, integrase inhibitor-based or multiclass), estimated glomerular filtration rate ([eGFR] calculated using the Modification of Diet in Renal Disease [MDRD] equation), CD4 + T-cell count, and hematocrit (HCT), as previously described in our cohort [ 1 , 2 , 18 , 19 ]. Model results are presented as percentage change (95% confidence interval [CI]) in TFV-DP concentrations in DBS for every significant change in each SDoH.…”

“…Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), an objective pharmacologic measure of cumulative adherence, has been associated with viral suppression [ 1 ] and predicts future viremia in persons with human immunodeficiency virus (PWH) [ 2 ]. Current research acknowledges the importance of developing objective adherence metrics to replace less precise self-reported adherence [ 1 , 3 , 4 ].…”

An enzymatic assay to measure long-term adherence to pre-exposure prophylaxis and antiretroviral therapy

“…3 Quantifying concentrations of HIV drugs and their metabolites is an objective approach to measuring drug adherence. [18][19][20][21] Tenofovir disoproxil fumarate (TDF) is used in all PrEP regimens currently recommended by health organizations (e.g. WHO and US Centers for Disease Control) and is also used in ~58% of all ART regimens.…”

“…24,27 TFV-DP drug levels are associated with health outcomes such as viral suppression in PLHIV, 28 efficacy of PrEP in HIV-negative people at risk of infection, 29 engagement in mental health care 20 among PLHIV, and the risk of viral rebound in PLHIV. 21 Immunoassays were recently developed to measure TFV in urine and blood. [30][31][32][33] A competitive immunoassay in urine accurately classified 98% of participants in the TARGET study in Thailand who took a dose in the last 24 hours as adherent.…”

Adherence to Antiretroviral Therapy and Pre-exposure Prophylaxis: TARGETing the Ideal Measure

“…Pharmacological measures of adherence are based on the quantification of drug concentrations in various body fluids and matrices, including plasma, saliva, urine, cells, hair, and dried blood spots [5]. These measures provide objective evidence of drug intake, and many of them have been associated with clinical outcomes in both ART [6][7][8] and PrEP [9,10]. However, their main limitations have been misinterpretation, distinguishing adherence from biological variability [5], and the lack of real-time availability in the "front lines" of clinical care.…”