Brief Report: Short-Term Adherence Marker to PrEP Predicts Future Nonretention in a Large PrEP Demo Project: Implications for Point-of-Care Adherence Testing

Abstract

Background: Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/ emtricitabine(FTC)-based PrEP were critical for interpretation of efficacy in PrEP clinical trials, and there is increasing interest in using drug levels to tailor interventions for reengagement and adherence. Point-of-care immunoassays (POC) for TFV, which examine short-term adherence, are in development. However the ability of poor short-term and long-term adherence to predict future PrEP non-retention is unknown. Setting: Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project Methods: An adjusted Cox-proportional hazards model examined the relationship of dried blood spot (DBS) levels of FTC-triphosphate (FTC-TP) or TFV-diphosphate (TFV-DP), measures of short-term and long-term PrEP adherence, respectively, with future study non-retention. Results: Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By study end, 27% were lost to follow-up, 25% had at least one undetectable FTC-TP level indicating poor short-term adherence, and 29% had a drug level indicating sub-optimal long-term adherence (TFV-DP<700 fmol/punch). The strongest factor associated with future study non-retention using a binary drug-level cutoff was an undetectable DBS FTC-TP level [adjusted hazard ratio (AHR) 6.3; 95% confidence interval (CI) 3.8-10.2].

Real-Time Monitoring and Point-of-Care Testing: A Review of the Current Landscape of PrEP Adherence Monitoring

“…Indeed, metrics of PrEP adherence were strongly associated with future loss to follow-up in a US demonstration project study. 22 Similarly, we have seen that adherence monitoring for ART with serial viral load testing has been invaluable for chronic ART management. Strategies that enable healthcare workers to measure and understand not only their patients’ risk of nonadherence but also their adherence patterns over time might allow them to better allocate (what are often scarce) resources such as counseling, additional staff time, and employment of more sophisticated adherence support tools, to individuals and/or groups of individuals who most need them.…”

“…Real-time, objective measures of adherence for PrEP are essential to assess how and when people are taking medication, and to accelerate a clinical and/or other supportive response for those with inadequate adherence. 20 , 21 Quantifying and monitoring adherence to PrEP can identify those at risk of becoming lost to follow-up and therefore at greater risk of HIV infection, 22 those in need of additional layers of support to overcome barriers to PrEP (impending health insurance loss, harm reduction tools, logistical support such as tokens), and individuals who need enhanced adherence support (more frequent visits, pill boxes, smart pill bottles, etc.). Indeed, metrics of PrEP adherence were strongly associated with future loss to follow-up in a US demonstration project study.…”

REverSe TRanscrIptase Chain Termination (RESTRICT) for Selective Measurement of Nucleotide Analogs Used in HIV Care and Prevention

“…13 Measurement of TFV-DP and FTC-TP concentrations can provide information about short-term and long-term adherence and enable investigation of their implications in clinical practice and behavioral science studies. 5,10,11,[13][14][15][16] Liquid chromatography tandem mass spectrometry (LC-MS/MS) is the gold standard for measuring nucleotide analogs, 10,11,17,18 and was used in directly observed therapy trials to…”

Enzymatic Assay for Rapid Measurement of Antiretroviral Drug Levels

“…TFV-DP is a nucleotide reverse transcriptase inhibitor (NRTI) that terminates the DNA chain when HIV reverse transcriptase (HIV RT) synthesizes complementary DNA (cDNA). TFV has a short half-life (15 h) in plasma and is detectable for up to 7 days. , TFV measurement is susceptible to the “white coat” effect, where one is unable to correctly identify patients who take their medications just before a doctor’s office visit . Conversely, TFV-DP has a longer half-life (17 days) and accumulates 25-fold in red blood cells (RBCs) and thus provides adherence information over 1–2 months .…”

“…18,19 TFV measurement is susceptible to the "white coat" effect, where one is unable to correctly identify patients who take their medications just before a doctor's office visit. 20 Conversely, TFV-DP has a longer half-life (17 days) and accumulates 25-fold in red blood cells (RBCs) and thus provides adherence information over 1−2 months. 19 TFV-DP concentrations are associated with health outcomes such as viral suppression 21 and PrEP efficacy.…”