Tenofovir is detected in urine and predicts HIV Viral Rebound and Drug Resistance
Point-of-care (POC), adherence testing using a urine tenofovir test (TFV) predicts both drug resistance and viral rebound in HIV-infected patients on antiretroviral treatment (ART). These findings were published by Clinical Infectious Disorders.
This case-control study was part of an open-label, randomized, non-inferiority, phase 3 study in South Africa. Researchers evaluated the safety of dolutegravir and tenofovir alafenamide, emtricitabine (FTC) in HIV patients who were eligible to receive first-line ART. Patients (cases), who experienced viral rebound at week 24 or later were matched against patients (controls). Patients in the case and control group were matched by trial arm. The time point at which patients in each case group developed viremia was recorded. Evaluation of the POC urine-TFV testing as a predictor of drug efficacy outcomes.
The median age of patients in the case (n=145), control (n=53), and 60.7% (IQR) groups was 30.0 (IQR 24.0-37.0) years, respectively. The median CD4 count at ART initiation were 309 (IQR 148-446) cells/mm and 365 (IQR 244-530).3 (P =.027), respectively.
The HIV viral loads at failure in patients in the case group ranged from 200 to 399 copies/mL (16.6%), 400-999 copies/mL (14.5%), and more than 1000 copies/mL (69.0%). The mean [SD] Number of 12-week viral load results measured at 200 copies/mL (or more) was 1.59 [1.02]67.6% of patients received viral resuppression.
The index visit revealed that urine tests showed that TFV was detectable in all patients in the control and one-third (34.5%) in the case groups.P <.001). Similar percentages of patients in the case and control groups had at least one detectable urine-TFV result at any time point in which viral rebound occurred (100% vs. 39.3%). P <.001).
Researchers discovered that urine-TFV testing could detect HIV virologic rebound with a sensitivity of 66%, and a specificity at 100%.P <.001). Similar diagnostic errors were observed at the sample level in a cross sectional analysis as well as subanalyses of patients receiving EFV (sensitivity, 69%, specificity, 100%; P <.001) or DTG (sensitivity, 70%; specificity, 100%; P <.001).
One subset (n=42), of patients who experienced virologic fail and had available sequencing data, confirmed nucleos (t)ide reverse transcriptase inhibition (NRTI), resistance was observed in 55.6% and 8.3% respectively of patients with one or more detectable urine TFV results.
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These results support clinical implementation and rapid insight into drug resistance during ART.
The urine-TFV test had an 83% sensitivity and 73% specificity. It also had a positive predictive value (56%), and a negative predictive value (92%) for predicting drug resistance in patient-level longitudinal analyses. A detectable urine TFV at any point was significantly predictive for NRTI resistance (odds ratio). [OR], 12.8; 95% CI, 2.1-144.8; P =.001).
Multivariable logistic regression analysis was performed by the researchers to determine correlations between drug level testing results and virologic outcomes. Patients who experienced viral rebound had a lower viral load (adjusted OR, 0.44; 95%CI, 0.27-0.68). P <.001) and lower CD4 cell counts at treatment initiation (adjusted OR, 0.75; 95% CI, 0.62-0.90; P =.003).
This study has some limitations, including the small sample size, retrospective POC urine testing, and the absence of a cost-effectiveness analysis.
“These results support clinical implementation of point-of-care TFV urine detection to rapidly provide insight into adherence, suppression, and drug resistance during ART,” the researchers concluded.
Disclosure: Multiple authors have declared affiliations to the industry. For a complete list of disclosures, please refer to the original reference.
