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

Autor: Tracy Kellermann, Monica Gandhi, Eric H Decloedt, Gert U. van Zyl, Matthew A Spinelli, Zukiswa Nkantsu, Marije van Schalkwyk, Dolphina Cogill, Catherine Orrell, Lauren Jennings
Rok vydání: 2022
Předmět:
Zdroj: AIDS Res Hum Retroviruses
ISSN: 1931-8405
0889-2229
Popis: Introduction The high cost of viral load (VL) testing limits its use for antiretroviral treatment (ART) adherence support. A low-cost lateral flow urine tenofovir (TFV) rapid assay predicts PrEP 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 increased risk of virologic failure. Methods 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 (DP) analysed in dried blood spots. VL testing was done concurrently and, if viremic, genotypic HIV drug resistance testing performed. Results Of 48 participants, 18 (37.5%) had virologic failure (VL>400 copies/mL) at the time of the study including 16 of 39 receiving efavirenz (EFV), 2 of 6 receiving protease inhibitors (PI) and 0 of 3 receiving dolutegravir (DTG). 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 2 out of 3 without regimen-relevant resistance; p=0.02. Conclusion In participants on EFV-based regimens returning to care, virologic failure 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.
Databáze: OpenAIRE