Measuring the concentration of tenofovir in a patient’s urine can determine their recent adherence to pre-exposure prophylaxis, or PrEP, for HIV prevention or tenofovir-based ART, according to findings from the Tenofovir Adherence to Rapidly Guide and Evaluate PrEP and HIV Therapy, or TARGET, study.
“Maintaining adherence to PrEP or ART is often challenging for clients and patients, and their providers don’t have the tools to know who needs additional support or help. There are several measurements of adherence, including pill counting, but these methods are not accurate or reliable,” Paul K. Drain, MD, MPH, assistant professor of global health and allergy and infectious diseases at the University of Washington, told Infectious Disease News.
“Direct measurement of tenofovir can provide a more accurate and helpful method for monitoring adherence,” Drain said. “Until now, we have not had data to describe the urine tenofovir concentrations among adults with known (or controlled) levels of adherence.”
TARGET included 28 HIV-uninfected adults who were randomly assigned to receive controlled dosing of 300 mg of tenofovir disoproxil fumarate (TDF) and 200 mg of emtricitabine in one of three groups. Participants in the “perfect” adherence group received the medication daily, those in the “moderate” adherence group received four doses a week and those in the “low” adherence group received two doses a week.
The mean age of participants was 33 years, and 57% were male. According to the study, the researchers observed a strong correlation between tenofovir (TFV) plasma and urine concentrations (P < .0001), and a significant difference in trough TFV concentrations at steady state between the adherence groups for plasma (P < .0001) and urine (P < .0002). Washout urine TFV concentrations and time-to-undetectable concentrations did not differ between the adherence groups, they reported.
Median steady-state trough TFV concentrations were 41 (interquartile range [IQR], 26-52) for perfect adherence and 16 (IQR, 14-19) and 4 (IQR, 3-5) for moderate and low adherence, respectively, in plasma, Drain and colleagues reported. In urine, they were 6,480 (IQR, 3,940-14,300) for perfect adherence, 3,405 [IQR, 2,210-5,020] for moderate adherence and 448 [IQR, 228-675] for low adherence.
TFV concentrations persisted longer in urine samples compared with plasma samples after participants stopped receiving medication.
“The results of our study showed that urine TFV concentrations can inform interpretation of novel point-of-care urine-based tenofovir assays to assess recent adherence,” Drain said. “The next step is to finalize our tenofovir assay and then to conduct clinical field studies to determine if the testing and feedback can help clients and patients improve their PrEP/ART adherence. Those studies will be starting soon. The results of those studies will be critical to help prevent HIV infection for clients receiving PrEP, and to prevent the emergence of drug-resistant HIV virus (for those receiving ART).”
Drain explained that the test being developed will only measure TFV in a urine samples and will not measure other HIV drugs or drugs of abuse.
“We need to be very careful to distinguish the new urine tenofovir assay from urine toxicology screening tests for drugs of abuse,” Drain said. “We hope that the point-of-care urine test can be helpful for helping people maintain adherence to PrEP or ART and will not be used to penalize people. In this regard, we’ll need the support of the HIV community, including PrEP clients and people living with HIV.”
In a related editorial, Jose R. Castillo-Mancilla, MD, associate professor in the division of infectious diseases at the University of Colorado School of Medicine, explained that the findings must be examined within the context of TARGET’s strengths and potential limitations. He noted that the strengths included its design and the focus on TFV concentrations in urine, whereas the potential limitations were the “considerable” overlap in the biological variability of TFV urine concentrations and “the short half-life and lack of accumulation of TFV in plasma and urine.”
“Based on the TARGET results, TFV would be most helpful to determine absence of recent dosing within the preceding week, and could be included in the armamentarium of available tools to identify patients with significant adherence gaps, in particular once it becomes available as a point-of-care test. Future studies evaluating the utility of this method will be indispensable to understand its clinical application in PrEP and ART,” Castillo-Mancilla wrote. – by Marley Ghizzone
Disclosures: Drain reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Castillo-Mancilla reports receiving funding from NIH/NIAID.