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

Abstract

IntroductionNovel point‐of‐care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout.MethodsWe conducted a cross‐sectional evaluation among PLHIV receiving first‐line ART containing tenofovir disoproxil fumarate at enrolment into a randomized trial in two South African public sector clinics. We calculated the diagnostic accuracy of the Abbott point‐of‐care immunoassay to detect urine TFV compared to liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). We evaluated the association between point‐of‐care urine TFV results and self‐reported adherence, viraemia ≥1000 copies/ml and HIV drug resistance, among people receiving either efavirenz or dolutegravir‐based ART.ResultsBetween August 2020 and March 2022, we enrolled 124 participants. The median age was 39 (IQR 34–45) years, 55% were women, 74 (59.7%) were receiving efavirenz and 50 (40.3%) dolutegravir. The sensitivity and specificity of the immunoassay to detect urine TFV ≥1500 ng/ml compared to LC‐MS/MS were 96.1% (95% CI 90.0−98.8) and 95.2% (75.3−100.0), respectively. Urine TFV results were associated with short (p<0.001) and medium‐term (p = 0.036) self‐reported adherence. Overall, 44/124 (35.5%) had viraemia, which was associated with undetectable TFV in those receiving efavirenz (OR 6.01, 1.27−39.0, p = 0.014) and dolutegravir (OR 25.7, 4.20−294.8, p<0.001). However, in those with viraemia while receiving efavirenz, 8/27 (29.6%) had undetectable urine TFV, compared to 11/17 (64.7%) of those receiving dolutegravir. Drug resistance was detected in 23/27 (85.2%) of those receiving efavirenz and only 1/16 (6.3%) of those receiving dolutegravir. There was no association between urine TFV results and drug resistance.ConclusionsAmong PLHIV receiving ART, a rapid urine TFV immunoassay can be used to accurately monitor urine TFV levels compared to the gold standard of LC‐MS/MS. Undetectable point‐of‐care urine TFV results were associated with viraemia, particularly among people receiving dolutegravir.Trial registrationPan‐African Clinical Trials Registry: PACTR202001785886049.

Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir-based antiretroviral therapy

“…Our study suggests that with the global dolutegravir rollout, urine TFV or DBS TFV-DP measures of adherence may be increasingly useful to measure adherence and complement viral load testing. Qualitative point-of-care urine TFVassays have been validated [5][6][7][8], and their clinical effectiveness will need to be confirmed in clinical trials before they can be rolled out in clinical practice [15]. Although TFV-DP performed better in our study, it currently requires expensive LC-MS/MS, which limits widespread clinical use in LMICs.…”

“…Lastly, among 250 virally suppressed PWH receiving efavirenz in South Africa, baseline TFV-DP less than 400 fmol/punch was associated with increased odds of developing viraemia at least 400 copies/ml after 1 month [11]. Regarding urine TFV levels, several studies demonstrate qualitative point-of-care urine TFV levels are associated with concurrent viraemia [5][6][7][8], but no studies have assessed the relationship between quantitative TFV concentrations and viraemia.…”

“…TFV is excreted in urine and correlates with short-term adherence as it has a 12-15 h terminal half-life [3], whereas TFV-DP accumulates in red blood cells and correlates with medium-term adherence as it has a longer half-life of 17 days [4]. Studies have shown that qualitative urine TFV [5][6][7][8] and quantitative dried blood spot (DBS) TFV-DP levels [9][10][11] are associated with viral suppression in PWH receiving ART, but none have compared the two measures, or determined thresholds that best predict viral suppression. Furthermore, dolutegravir has a higher genetic barrier to resistance than efavirenz, meaning that measures of adherence should be more closely associated with viral suppression, unlike efavirenz where resistance can cause viraemia despite good adherence.…”

Comparing a point‐of‐care urine tenofovir lateral flow assay to self‐reported adherence and their associations with viral load suppression among adults on antiretroviral therapy

“…Our study took place prior to the scale-up of DTG in South Africa which has implications for the development of resistance. A recent South African study found that the absence of TFV in urine was more strongly associated with viraemia among people receiving DTG, compared to efavirenz [20]. Recent evidence in the context of high genetic-barrier regimens (DTG-boosted or ritonavir-boosted protease inhibitor-based regimens) has shown that presence of TFV in urine could still be valuable to screen for potential resistance, despite the overall lower incidence of resistance [21].…”