ARV-associated Nephrotoxicity

 Renal abnormality* ARV  Management

Proximal tubulopathy with any combination of:

  1. Proteinuria: urine dipstick ≥ 1, or confirmed increase in UP/C >15 mg/mmoL(i)
  2. Progressive decline in eGFR and eGFR ≤ 90 mL/min(ii)
  3. Phosphaturia(iii): confirmed hypophosphataemia secondary to increased urine phosphate leak
  4. Glucosuria in non-diabetics


  • Tests for proximal renal tubulopathy/renal Fanconi syndrome(iii)
  • Consider renal bone disease if hypophosphataemia of renal origin: measure 25(OH) vitamin D, PTH, DXA

Replace TDF by non-tenofovir drug or TAF*** if:

  • Documented tubular proteinuria and/or glucosuria                   
  • Progressive decline in eGFR and no other cause
  • Confirmed hypophosphataemia of renal origin and no other cause
  • Osteopenia/osteoporosis in the presence of increased urine phosphate leak
  1. Crystalluria
  2. Haematuria(iv)
  3. Leukocyturia
  4. Loin pain
  5. Acute renal insufficiency
  • Urinalysis for crystalluria/stone analysis
  • Exclude other cause for nephrolithiasis
  • Renal tract imaging including CT scan

Consider stopping IDV/ATV if:

  • Confirmed renal stones
  • Recurrent loin pain +/- haematuria
Interstitial nephritis:
  1. Progressive decline in eGFR(ii)
  2. Tubular proteinuria(ii)/haematuria
  3. Eosinophiluria (if acute)
  4. Leukocyte casts


  • Renal ultrasound
  • Refer to nephrologist

Consider stopping IDV/ATV if:

  • Progressive decline in eGFR and no other cause

Progressive decline in eGFR, but none of the above(v)


Complete assessment

Consider stopping ARVs with potential nephrotoxicity if:

  • Progressive decline in eGFR and no other cause(v)


* Use of DTG, RPV, COBI and PI/r is associated with an increase in serum creatinine/reduction of eGFR (10-15 mL/min/1.73m2) due to inhibition of proximal tubular creatinine transporters without impairing actual glomerular filtration: consider new set point after 1-2 months

** TAF has shown lower tenofovir-related renal adverse effects due to lower systemic tenofovir exposure. Switch-studies from TDF to TAF suggest potential reversion of renal toxicity, however, long-term experience with TAF is lacking

*** Particularly if eGFR > 30 mL/min, as there are limited data to on use of TAF with eGFR ≤ 30 mL /min, and longer term outcomes are unknown

  1. UP/C in spot urine detects total urinary protein including protein of glomerular or tubular origin. The urine dipstick analysis primarily detects albuminuria as a marker of glomerular disease and is inadequate to detect tubular disease
  2. For eGFR: use CKD-EPI formula. The abbreviated MDRD (Modification of Diet in Renal Disease) or the Cockcroft-Gault (CG) equation may be used as an alternative, see
  3. See Indications and Tests for Proximal Renal Tubulopathy (PRT)
  4. Microscopic haematuria is usually present
  5. Different models have been developed for calculating a 5-years CKD risk score while using different nephrotoxic ARVs integrating HIV-independent and HIV-related risk factors [12], [13]