NEW YORK (Reuters Health) – The level of emtricitabine triphosphate (FTC-TP), an anabolite of emtricitabine, in dried blood spots (DBS) predicts HIV viral suppression and reflects short-term adherence to therapy, researchers report.
“We know that tenofovir diphosphate (TFV-DP) in DBS is a very powerful measure of cumulative adherence, and that it has a strong association with HIV viral load,” said Dr. Jose Castillo-Mancilla of the School of Medicine, University of Colorado Anschutz Medical Campus, in Aurora.
“Finding that FTC-TP (a measure of recent dosing) can provide some additional information beyond TFV-DP was very interesting,” he told Reuters Health by email.
TFV-DP is best used as a marker of adherence over the preceding six to eight weeks, whereas FTC-TP reflects recent dosing because of its shorter half-life in both red blood cells and DBS.
Dr. Castillo-Mancilla and colleagues investigated the association of FTC-TP in DBS as a predictor of HIV viral suppression and evaluated self-reported adherence as a predictor of FTC-TP in their study of more than 1,100 clinical visits from 514 people living with HIV.
A third of the patients were viremic and two-thirds were suppressed at baseline. During follow-up, 16% of patients who were suppressed at baseline became viremic at one of the follow-up visits, while 52% of those who were viremic at baseline became suppressed at one of the follow-up visits.
After adjusting for various factors, the odds of viral suppression were 7.2-fold higher when FTC-TP was quantifiable than when it was not. In multivariable analysis, the odds of viral suppression were 2.1-fold higher after including TFV-DP in the analysis.
Among viremic patients, the proportion of quantifiable FTC-TP in DBS increased with each adherence category for the three-day, 30-day, and three-month adherence measures, the researchers report in the Journal of Antimicrobial Chemotherapy, online January 18.
On the other hand, the proportion of quantifiable FTC-TP increased significantly with each adherence category only for the three-day adherence measure among patients with viral suppression.
“Pharmacologic measures of antiretroviral therapy (ART) adherence and exposure, such as FTC-TP and TFV-DP in DBS, allow us to objectively quantify adherence and could help us optimize HIV management in the future,” Dr. Castillo-Mancilla said.
Dr. Raphael J. Landovitz from UCLA Center for Clinical AIDS Research and Education, in Los Angeles, who recently reported on the use of plasma tenofovir levels as a biomarker for ART adherence, told Reuters Health by email, “Self-reports of adherence are fraught with social desirability bias (what doctors want to hear; or what patients think doctors want to hear) and/or recall bias (honest misremembering). It’s very helpful in clinical practice to have a biomarker of adherence that is a point of intervention – we still need better support interventions for low adherence, however.”
“The power of the DBS matrix should really not be underestimated – the TFV-DP assay provides a long-term-horizon estimate of average adherence, and the FTC-TP matrix provides a short-term-horizon estimate of adherence – together, a simple blood spot can provide an enormous wealth of adherence information for individuals with HIV and provide a unique opportunity to optimize outcomes through insights into patients’ pill-taking behavior, really as never before,” said Dr. Landovitz, who was not involved in the study.
Dr. Jessica E. Haberer from Massachusetts General Hospital and Harvard Medical School, in Boston, has researched various aspects of ART adherence. She told Reuters Health by email, “I think this assay would be most useful for clinical care if it were available at the point-of-care. Real-time, objective information about non-adherence could be used as a conversation starter for patients who are reticent to discuss their adherence challenges. This information could enable better counseling and/or provision of support services. Waiting for similar data at the next appointment would not likely be as effective.”
“Adherence is challenging to measure and all methods have limitations,” said Dr. Haberer. “This assay can be used in conjunction with longer-term measures, like TFV-DP, to get a more complete picture of adherence behavior.”
She added, “Low-cost point-of-care assays for adherence could be of great use for determining the cause of viremia in developing settings where drug resistance testing is not available. I would encourage these and other researchers to pursue such technology.”
Dr. Helen C. Koenig, Medical Director of the McGregor Infectious Diseases Clinic, Hospital of the University of Pennsylvania, in Philadelphia, has shown that a urine assay for tenofovir can successfully monitor adherence to preexposure prophylaxis (PrEP).
“Objective markers of adherence, both short-term and long-term, can add critical information to the care of a patient living with HIV and for patients taking PrEP. Exactly what form of objective monitoring and how to incorporate that monitoring should be further explored in demonstration projects,” she told Reuters Health by email.
“Ideally it would be a point-of-care assay that could be done when patients are checking in, such that the provider already has some adherence information when they see the patient,” said Dr. Koenig, who also was not involved in the study. “The only downside is that it’s a finger prick, which may not be acceptable to all patients and could potentially act as a barrier to patients coming in for their appointments.”
J Antimicrob Chemother 2019.