Point-of-care (POC) adherence testing using a urine-based tenofovir (TFV) test predicts both viral rebound and drug resistance with high specificity among patients with HIV infection receiving antiretroviral therapy (ART). These findings were published in Clinical Infectious Diseases.
This case-control study was nested within an open-label, randomized, noninferiority phase 3 study that was conducted in South Africa. In patients with HIV infection who were eligible for first-line ART, researchers evaluated the safety and efficacy of dolutegravir (DTG) plus tenofovir alafenamide and emtricitabine (FTC); DTG plus tenofovir disoproxil fumarate (TDF) and FTC; and efavirenz (EFV) plus TDF and FTC through week 96. Patients (cases) who experienced viral rebound at week 24 of follow-up or later were matched 4:1 against patients (controls) without viral rebound. Patients in the case and control groups were matched by trial arm and assessed at the timepoint at which patients in the case group developed viremia. The performance of POC urine-TFV testing for predicting drug efficacy outcomes was evaluated.
Among patients in the case (n=145) and control (n=53) groups, the median age was 30.0 (IQR, 24.0-35.0) and 31.0 (IQR, 26.0-37.0) years, 60.7% and 64.2% were women, and the median CD4 count at ART initiation was 309 (IQR, 148-446) and 365 (IQR, 244-530) cells/mm3 (P =.027), respectively.
Among patients in the case group, HIV viral loads at failure were between 200 and 399 copies/mL in 16.6% of patients, between 400-999 copies/mL in 14.5%, and at more than 1000 copies/mL in 69.0%. The mean [SD] number of 12-week viral load results measured at 200 copies/mL or more was 1.59 [1.02], and 98 patients (67.6%) achieved viral resuppression.
At the index visit, urine test results showed detectable TFV among all patients in the control group and one-third (34.5%) of those in the case group (P <.001). A similar percentage of patients in the control vs case groups had at least 1 detectable urine-TFV test result at any timepoint in which viral rebound occurred (100% vs 39.3%; P <.001).
The researchers found that urine-TFV testing had a sensitivity of 66% and a specificity of 100% for diagnosing HIV virologic rebound (P <.001). Similar diagnostic accuracies were observed at the sample level in a cross-sectional analysis, as well as in subanalyses among patients receiving either EFV (sensitivity, 69%; specificity, 100%; P <.001) or DTG (sensitivity, 70%; specificity, 100%; P <.001).
Among a subset of patients (n=42) who experienced virologic failure and had available sequencing data, confirmed nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance was observed among 55.6% of those with 1 or more detectable urine-TFV results and among 8.3% of those with continuous undetectable urine-TFV results.
The urine-TFV test had a sensitivity of 83%, a specificity of 73%, a positive predictive value of 56%, and a negative predictive value of 92% for predicting drug resistance in the patient-level longitudinal analysis. A detectable urine-TFV at any timepoint was significantly predictive of NRTI resistance (odds ratio [OR], 12.8; 95% CI, 2.1-144.8; P =.001).
The researchers performed a multivariable logistic regression analysis to determine correlations between virologic outcomes and drug level testing results. In patients who experienced viral rebound, a detectable urine-TFV result was associated with both lower viral load at the time of rebound (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).
Limitations of this study include the small sample size, the fact that POC urine tests were performed retrospectively, and the lack of a cost-effectiveness assessment.
“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 declared affiliations with industry. Please see the original reference for a full list of disclosures.
Hermans LE, Umunnakwe CN, Lalla-Edward ST, et al. Point-of-care tenofovir urine testing for the prediction of treatment failure and drug resistance during initial treatment for HIV-1 infection. Clin Infect Dis. Published online September 22, 2022. doi:10.1093/cid/ciac755