What is the recommended dosing for TAF (tenofovir alafenamide), dolutegravir, and lamivudine in an HIV patient with impaired renal function (creatinine clearance of 34 mL/min)?

Dosing Recommendations for TAF + Dolutegravir + Lamivudine with CrCl 34 mL/min

This regimen requires dose adjustment: TAF can be used at standard dose (25 mg daily), dolutegravir requires no adjustment (50 mg daily), but lamivudine must be reduced to 150 mg once daily for a creatinine clearance of 30-49 mL/min. 1

Individual Drug Dosing Adjustments

Tenofovir Alafenamide (TAF)

• TAF can be used when creatinine clearance is above 30 mL/min/1.73 m² 1
• At CrCl 34 mL/min, standard dosing of TAF 25 mg daily is appropriate 1
• TAF is preferred over tenofovir disoproxil fumarate (TDF) in renal impairment due to significantly lower nephrotoxicity 1, 2
• Critical distinction: TAF should be avoided if CrCl falls below 30 mL/min 1

Dolutegravir

• No dose adjustment required for any level of renal impairment 3
• Dolutegravir is not primarily renally eliminated and can be used safely in chronic kidney disease 3
• Note that dolutegravir blocks tubular creatinine secretion, causing a 10% increase in measured creatinine without affecting true glomerular filtration rate 1

Lamivudine

• Dose reduction is mandatory for CrCl below 50 mL/min 1
• For CrCl 30-49 mL/min: 150 mg once daily 1
• Standard dosing (300 mg daily or 150 mg twice daily) is only appropriate when CrCl ≥50 mL/min 1
• Further reduction required if CrCl drops below 30 mL/min: 150 mg first dose, then 100 mg daily for CrCl 15-29 mL/min 1

Clinical Considerations and Monitoring

Fixed-Dose Combination Limitations

• Most fixed-dose combination tablets are contraindicated when GFR falls below 50 mL/min 1
• This patient requires individual component dosing rather than a single-tablet regimen 1
• The inability to adjust individual drug doses in fixed combinations necessitates separate prescriptions 1

Renal Function Monitoring

• Monitor renal function closely as CrCl of 34 mL/min is near the threshold for TAF use 1
• Reassess creatinine clearance regularly, as further decline below 30 mL/min would require switching from TAF 1, 2
• Remember that dolutegravir will artificially increase serum creatinine by approximately 10% without true kidney injury 1

Alternative Considerations if Renal Function Declines

• If CrCl falls below 30 mL/min, consider switching to dolutegravir + lamivudine (dose-adjusted) without tenofovir 1, 3
• Dual therapy with dolutegravir and dose-adjusted lamivudine has demonstrated efficacy in patients with renal impairment 3
• Abacavir does not require renal dose adjustment and could replace TAF if needed, though cardiovascular risk assessment is warranted 1

Common Pitfall

• Do not use fixed-dose combination tablets (such as Biktarvy or Triumeq) in this patient - the inability to adjust lamivudine dosing makes these inappropriate 1
• Prescribers often overlook the need for lamivudine dose reduction at CrCl <50 mL/min, risking drug accumulation 1