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

• DOI: 10.1089/aid.2021.0135
• Publication Date: 2021-11-13T15:21:58Z
• Authors: Lauren Jennings; Tracy Kellermann; Matthew Spinelli; Zukiswa Nkantsu; Dolphina Cogill; Marije van Schalkwyk; Eric Decloedt; Gert van Zyl; Catherine Orrell; Monica Gandhi
• Keywords: Cyclopropanes; Anti-HIV Agents; Clinical Sciences; Clinical Trials and Supportive Activities; Drug Resistance; Clinical sciences; HIV Infections; resistance; South Africa; 03 medical and health sciences; 0302 clinical medicine; Clinical Research; Virology; Emtricitabine; Humans; adherence; Viremia; Tenofovir; real time; Biomedical and Clinical Sciences; Prevention; Viral Load; 16. Peace & justice; point of care; urine; 6. Clean water; Benzoxazines; 3. Good health; Mental Health; Infectious Diseases; Good Health and Well Being; Cross-Sectional Studies; Medical Microbiology; 5.1 Pharmaceuticals; Alkynes; HIV/AIDS; Antimicrobial Resistance; Patient Safety; Development of treatments and therapeutic interventions; Infection

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.