Tenofovir and emtricitabine concentrations in hair are comparable between individuals on tenofovir disoproxil fumarate versus tenofovir alafenamide‐based ART

Abstract

Tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) is the backbone for both human immunodeficiency virus (HIV) treatment and pre-exposure prophylaxis (PrEP) worldwide. Tenofovir alafenamide (TAF) with FTC is increasingly used in HIV treatment and was recently approved for PrEP among menwho-have-sex-with-men. TDF and TAF are both metabolized into tenofovir (TFV).Antiretrovirals in plasma are taken up into hair over time, with hair levels providing a long-term measure of adherence. Here, we report a simple, robust, highly sensitive, and validated high-performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS)-based analytical method for analyzing TFV and FTC from individuals on either TDF/FTC or TAF/FTC in small hair samples. TFV/FTC are extracted from $5 mg hair and separated on a column using a gradient elution. The lower quantification limits are 0.00200 (TFV) and 0.0200 (FTC) ng/mg hair; the assay is linear up to 0.400 (TFV) and 4.00 (FTC) ng/mg hair. The intra-day and inter-day coefficients of variance (CVs) are 5.39-12.6% and 6.40-13.5% for TFV and 0.571-2.45% and 2.45-5.16% for FTC. TFV concentrations from participants on TDF/FTC-based regimens with undetectable plasma HIV RNA were 0.0525 ± 0.0295 ng/mg, whereas those from individuals on TAF/FTC-based regimens were 0.0426 ± 0.0246 ng/mg. Despite the dose of TFV in TDF being 10 times that of TAF, hair concentrations of TFV were not significantly different for those on TDF versus TAF regimens. Pharmacological enhancers (ritonavir and cobicistat) did not boost TFV concentrations in hair. In summary, we developed and validated a sensitive analytical method to analyze TFV and FTC in hair and found that hair concentrations of TFV were essentially equivalent among those on TDF and TAF.

Dynamic choice HIV prevention intervention at outpatient departments in rural Kenya and Uganda

“…Among participants who reported taking any PrEP or PEP doses in the past 30 days at week 24, we collected small samples of scalp hair (50-100 strands) for analysis of hair concentrations of tenofovir. Drug levels in the 1 cm of hair closest to the scalp (reflecting the most recent month of drug exposure) were analyzed via liquid chromatography-tandem mass spectrometry using validated methods in the Hair Analytical Laboratory at the University of California, San Francisco [31,32].…”

Brief Report: No Difference in Urine Tenofovir Levels in Patients Living With HIV on Unboosted Versus Dose-Adjusted Boosted Tenofovir Alafenamide

“…We measured urine TFV levels by LC-MS/MS in the Hair Analytical Laboratory at the University of California San Francisco using methods validated inhouse for urine and akin to those previously published for hair. 14,15,22 We also reviewed each study participant's electronic medical record to confirm their ART regimen-including TAF dose (25 vs 10 mg) and presence/absence of pharmacologic booster-and to collect additional clinical variables (all at or around the time of urine sample collection) such as age, sex, weight, creatinine (most recent within 6 months before or after urine collection), and HIV viral load (most recently documented viral load around urine sample collection). We restricted this analysis to patients with viral suppression (most recent HIV RNA ,200 copies/mL) who also self-reported high adherence to ART, including having taken their antiretroviral drugs within the last 24 hours, on the study questionnaire.…”

“…We measured urine TFV levels by LC–MS/MS in the Hair Analytical Laboratory at the University of California San Francisco using methods validated in-house for urine and akin to those previously published for hair. 14,15,22…”

User Experience of Persons Using Ingestible Sensor–Enabled Pre-Exposure Prophylaxis to Prevent HIV Infection: Cross-Sectional Survey Study

“…In contrast to these surrogate technologies, ISs signal when medication reaches the gastric track and are able to capture individual daily behavior patterns in real time, providing insight into variations in daily medication adherence. This capacity even has advantages over cumulative metabolite-based adherence measures developed and evaluated in the HIV prevention arena, such as dried blood spots and hair analysis [27,28], which do not allow real-time intervention or capture pattern variations in medication ingestion over time [7]. Such patterns are of importance based on the postdose durations of the therapeutic drug [29,30], which alters the risk of acquiring HIV infection, for example, a week where PrEP is taken once, followed by a week where it is taken daily [31][32][33].…”