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FTC-TP in Dried Blood Spots Predicts
Future Detectable Viral Load in US Study
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CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021
Mark Mascolini
Undetectable emtricitabine-triphosphate (FTC-TP) in dried blood spots predicted future detectable viral load in a study of 433 US residents with HIV infection [1]. When someone taking an antiretroviral combination containing FTC and tenofovir disoproxil (TDF) has undetectable FTC-TP in blood spots but claims 100% adherence in the past 3 days, strong adherence counseling is in order. (FTC-TP is the active form of FTC in the body.)
Researchers from the University of Colorado Anschutz Medical Campus (UC-AMC), who conducted this study, noted that FTC-TP in dried blood spots is a good way to measure recent adherence to an FTC-containing regimen because FTC-TP has a half-life of 35 hours in blood spots. Detectable FTC-TP in blood spots also indicates current viral suppression, the UC-AMC team noted. But until this study no one tested the value of this measure in predicting future detectable viral load.
These investigators conducted a trial that enrolled people taking an FTC/TDF-containing regimen and made routine clinic visits for viral load testing [2]. The study aimed to assess the value of TDF in dried blood spots as a simple measure of TDF levels and to see whether levels correlated with adherence and viral suppression. The UC-AMC group reported those findings in 2019 [3]. With these same dried blood spots, they decided to see whether FTC-TP levels in the spots could predict future viremia.
People enrolled in the original trial from June 2014 through July 2017 and made up to 3 clinic visits in 48 weeks. At each visit clinic staff measured viral load, made dried blood spots from the person’s blood sample, and asked the person about their adherence to their antiretroviral combination in the past 3 days. Researchers measured FTC-TP and TFV-DP (the active form of TDF) in 3-mm punches from the spots and calculated concentrations of the drugs with a standard test. They divided FTC-TP results into one of two groups: (1) quantifiable and (2) below the limit of quantitation (measurable and unmeasurable). Their goal in this part of the study was to estimate chances of a future detectable viral load (above 20 copies) according to FTC-TP detectability in blood spot at the current visit.
The researchers had 677 dried blood spots, each linked to a viral load measure, from 433 people. Of these 433 people, 69 (16%) were female, 83 (19%) black, and 85 (20%) Hispanic. FTC-TP could not be detected in blood spots from 41 people (9.5%) and could be detected in blood spots from the remaining 392 people. The 41 people with unmeasurable FTC-TP did not differ much from the measurable group in proportions of males or females, in race or ethnicity, or in proportions who were normal weight, overweight, or obese. Median viral load was somewhat higher in the FTC-TP-unmeasurable group than in the measurable group (6620 vs 67 copies). Everyone in both groups reported 100% antiretroviral adherence in the past 3 days.
Compared with people who had measurable FTC-TP in their dried blood spot, those with unmeasurable FTC-TP had 4-fold higher odds of future viremia (detectable viral load) (odds ratio [OR] 4.1, 95% confidence interval [CI] 2.3 to 7.2, P < 0.0001).
When the researchers considered the impact of several other factors on that association-age, gender, race, body mass index, CD4 count, hematocrit (red blood cells in blood), and antiretroviral combination-unmeasurable FTC-TP in blood spots still more than tripled chances of future viremia (adjusted OR [aOR] 3.4, 95% CI 1.8 to 6.5, P = 00002). When the researchers also considered the impact of TFV-DP detectability in blood spots, unmeasurable FTC-TP almost doubled chances of future detectable viral load, but the association fell a little short of statistical significance (aOR 1.9, 95% CI 0.9 to 4.1, P = 0.090).
Next the researchers performed an interaction analysis involving self-reported adherence and unmeasurable or measurable FTC-TP in dried blood spots. When a person reported 100% adherence in the past 3 days and FTC-TP was unmeasurable in blood spots, that person had 6 times higher odds of future viremia than people who reported 100% adherence in the past 3 days and had measurable FTC-TP in blood spots (aOR 6.0, 95% CI 1.8 to 20.3, P = 0.001).
The UC-AMC group went on to estimate the percentage of people with a future detectable viral load according to FTC-TP in blood spots and less than 100% versus 100% self-reported 3-day adherence. For people with 100% self-reported 3-day adherence (like everyone in this study), 62% with unmeasurable FTC-TP in blood spots would have a future detectable viral load, whereas only 19% would measurable FTC-TP in blood spots would have a future detectable viral load.
The researchers proposed that measuring FTC-TP in dried blood spots could spot mismatches between adherence and drug concentration in people who reported 100% adherence in the past 3 days. They suggested that these mismatchers who report perfect adherence in the preceding 3 days but whose blood spot shows no measurable FTC-TP “could benefit from antiretroviral therapy adherence counseling regarding the risk of future viremia.”
The UC-AMC team noted that FTC-TP measurability in blood spots was less predictive of future detectable viral load than TFV-DP measurability in blood spots. They called for careful study of both TFV-DP and FTC-TP in blood spots over time (prospectively) as tools to track antiretroviral adherence in clinical practice.
References
1. Morrow M, MaWhinney S, Coyle R, et al. Emtricitabine triphosphate in dried blood spots predicts future viremia in PWH. CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021. Abstract 92.
2. ClinicalTrials.gov. Quantifying drug adherence and drug exposure to antiretroviral therapy (2104). ClinicalTrials.gov identifier NCT02012621. https://clinicaltrials.gov/ct2/show/NCT02012621
3. Morrow M, MaWhinney S, Coyle RP, et al. Predictive value of tenofovir diphosphate in dried blood spots for future viremia in persons living with HIV. J Infect Dis. 2019;220:635-642. doi: 10.1093/infdis/jiz144.
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