Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure

Abstract

Objective:We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART).Design:We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa.Methods:Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen.Results:Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% (n = 243/283). Of those with TFV detected on the POC assay, 91% (n = 204/224) had HIVDR, vs. only 66% (n = 39/59) among those with no TFV detected (P-value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively.Conclusions:In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.

Diagnostic accuracy of a point‐of‐care urine tenofovir assay, and associations with HIV viraemia and drug resistance among people receiving dolutegravir and efavirenz‐based antiretroviral therapy

“…As in our study, the prevalence of HIVDR was high among people with efavirenz (18/20, 90%), and much lower among those receiving dolutegravir (5/16 = 31%), although associations between HIVDR and urine TFV results were not evaluated. Two other studies, focusing on people with viraemia while receiving efavirenz, found associations between positive point-of-care urine TFV results and HIVDR mutations, but similar to our findings, the prevalence of HIVDR mutations was high, and so the pre-and post-test probabilities of HIVDR did not change much after a positive urine TFV test [18,24]. This is one of the first evaluations of the analytic performance of the Abbot point-of-care urine TFV assay, beyond the validation conducted as part of the assay's development [10].…”

“…Seventy-four (59.7%) were receiving efavirenz for a median of 4.2 years (2.1-6.0), and 50 (40.3%) were receiving dolutegravir, for a median of 0.6 years (0.5-1.0). Median time since the pre-enrolment viraemic VL was 15 days (13)(14)(15)(16)(17)(18)(19)(20)(21). In December 2020, we were informed that 1).…”

Quantification of Antiviral Drug Tenofovir (TFV) by Surface-Enhanced Raman Spectroscopy (SERS) Using Cumulative Distribution Functions (CDFs)

“…TFV is a main component of the first-line highly active ARV therapy (ART) for the treatment of HIV globally. , In combination with emtricitabine, another NRTI, TFV is also used to prevent HIV when taken as a daily pre-exposure prophylaxis (PrEP) regimen . High adherence to these medication regimens, particularly when prescribed for ART, is important in order for the treatment to remain effective and prevent viral rebound as well as the emergence of resistant viruses. , Detection and quantification of TFV and its metabolites in biological matrices such as plasma and blood cells have been used as objective markers of adherence in clinical trial participants, allowing the identification of those who are compliant with the protocol. − This, in turn, is important to assessing the true effect of the experimental intervention. Previous work in our laboratory has shown that while this quantification was possible using the entire SERS surface generated by the evaporative process described above, the analytical sensitivity was enhanced by selecting SERS spectra corresponding to high signal-to-noise ratio (S/N) as a function of spatial position using a scanning Raman system to acquire spatially resolved spectra.…”

Point-of-care urine tenofovir testing: making a good thing better

“…In this issue of AIDS, McCluskey et al [3] show us how such a strategy can be implemented. A total of 289 patients enrolled in a clinical trial and receiving TFV with either lamivudine or emtricitabine (3TC/FTC) along with either efavirenz (95%) or nevirapine (5%) and having HIV plasma viral load (HIV-VL) measures 1000 copies/ ml (c/ml) were identified.…”

“…In conclusion, McCluskey et al [3] suggest that a simple, POC urine TFVassay can be used to determine whether a patient is taking a prescribed antiviral regimen or not in the setting of detectable HIV-VL levels. It should find its best application in the context of INSTI-based regimens with a higher barrier to resistance, such as DTGcontaining regimens, with confirmatory studies needed to validate this application.…”