Drug Resistance, Rather than Low Tenofovir Levels in Blood or Urine, Is Associated with Tenofovir, Emtricitabine, and Efavirenz Failure in Resource-Limited Settings

Abstract

The high cost of viral load (VL) testing limits its use for antiretroviral therapy (ART) adherence support. A low-cost lateral flow urine tenofovir (TFV) rapid assay predicts pre-exposure prophylaxis breakthroughs, but has not yet been investigated in HIV treatment. We therefore evaluated its utility in a pilot cross-sectional study of TFV-containing ART recipients at an increased risk of virologic failure (VF). Participants who had a treatment interruption ≥30 days or had ≥1 episode of viremia (VL ≥400 copies/mL) in the previous year were recruited from a public health setting in Cape Town, South Africa. Self-reported adherence data were collected, the urine TFV assay performed, and concurrent TFV-diphosphate analyzed in dried blood spots. VL testing was done concurrently and, if viremic, genotypic HIV drug resistance testing was performed. Of 48 participants, 18 (37.5%) had VL (>400 copies/mL) at the time of the study, including 16 of 39 receiving efavirenz (EFV), 2 of 6 receiving protease inhibitors, and 0 of 3 receiving dolutegravir. Resistance testing succeeded in 17/18, of which 14 had significant mutations compromising ≥2 agents of the current EFV-based regimen. Of these 14, all had detected urine TFV. Urine TFV was undetectable in two out of three without regimen-relevant resistance; p = .02. In participants on EFV-based regimens returning to care, VF was largely due to viral resistance, where detectable urine TFV had 100% sensitivity (14/14 participants) in predicting resistance. Conversely, when undetectable, the urine-based assay could be used to preclude participants with poor adherence from undergoing costly HIV drug resistance testing.

Keywords: adherence; point of care; real time; resistance; urine.

FIG. 1.

The full cohort of 48 participants who had results for UTRA, VL, and TFV-DP concentration in DBS categorized by (1) UTRA results, (2) VL results, and (3) HIV drug resistance results. DP, diphosphate.

FIG. 2.

TFV-DP in DBS in patients categorized by (a) UTRA results and (b) VL failure category (above or below 400 copies/mL). There were significantly lower TFV-DP concentrations in participants who were UTRA negative (p = .02), but the difference in TFV-DP between participants with VF versus suppression was not significant (p = .5). DBS, dried blood spots; TFV-DP, tenofovir diphosphate; UTRA, urine tenofovir rapid assay; VF, virologic failure; VL, viral load.