From the Guidelines
In patients with chronic kidney disease (CKD), the use of lamivudine, dolutegravir, and tenofovir requires careful consideration, with a preference for tenofovir alafenamide (TAF) over tenofovir disoproxil fumarate (TDF) due to its lower renal toxicity, as recommended by the 2020 guidelines of the International Antiviral Society-USA panel 1.
Key Considerations for Each Medication:
- Lamivudine: Dosing should be reduced in CKD patients, with a 50% dose reduction when creatinine clearance is below 50 mL/min and 25-30% of the normal dose for patients with clearance below 30 mL/min, as per guidelines from the HIV Medicine Association of the Infectious Diseases Society of America 1.
- Dolutegravir: Generally does not require dose adjustment in CKD as it is primarily metabolized by the liver.
- Tenofovir:
- TDF requires dose reduction or extended dosing intervals when creatinine clearance falls below 50 mL/min and is not recommended when clearance is below 10 mL/min.
- TAF is preferred in CKD due to less renal toxicity and can be used without dose adjustment until very advanced kidney disease, but its use should be considered with caution when the creatinine clearance rate is below 30 mL/min/1.73 m2, as suggested by the 2020 recommendations 1.
Monitoring and Adjustments:
Regular monitoring of renal function is essential, particularly with TDF, which can cause tubular dysfunction. The reduced renal clearance in CKD patients leads to drug accumulation and potential toxicity if doses aren't adjusted appropriately. TAF results in lower plasma tenofovir levels and reduced renal toxicity compared to TDF.
Clinical Decision Making:
When considering an antiretroviral therapy (ART) switch from TDF, it is crucial to exclude other common causes of kidney dysfunction. For individuals with progressive kidney dysfunction, tenofovir should be avoided if possible, but if not, TAF/emtricitabine can be used when the creatinine clearance rate is above 30 mL/min/1.73 m2, emphasizing the importance of renal function monitoring and dose adjustments to prevent further kidney damage, as outlined in the clinical practice guidelines for the management of CKD in HIV-infected patients 1.
From the FDA Drug Label
2)]. No dose adjustment of tenofovir disoproxil fumarate tablets 300 mg is necessary for patients with mild renal impairment (creatinine clearance 50 to 80 mL/min).
2 New Onset or Worsening Renal Impairment Tenofovir is principally eliminated by the kidney.
6 Patients with Impaired Renal Function Reduction of the dosage of lamivudine is recommended for patients with impaired renal function [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].
Dosing in CKD patients:
- Tenofovir: No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50 to 80 mL/min). However, dosing interval adjustment is recommended in patients with creatinine clearance below 50 mL/min.
- Lamivudine: Reduction of the dosage is recommended for patients with impaired renal function.
- Dolutegravir: There is no information provided in the given drug labels regarding dosing in CKD patients. Therefore, caution is advised when using these medications in CKD patients, and dosing adjustments should be made according to the individual patient's renal function and the specific medication being used 2, 3.
From the Research
Antiretroviral Regimens in CKD Patients
- The use of antiretroviral regimens in patients with chronic kidney disease (CKD) requires careful consideration of the potential nephrotoxic effects of certain medications 4, 5.
- Lamivudine, dolutegravir, and tenofovir are commonly used antiretroviral medications, but their use in CKD patients may require dose adjustments or alternative regimens 6, 7.
Dose Adjustments and Alternative Regimens
- Lamivudine dose adjustments may be necessary in patients with reduced renal function, but dual therapy with lamivudine and dolutegravir has been shown to be effective in controlling viral load in older patients with comorbidities, including renal impairment 6.
- Tenofovir alafenamide (TAF) is a alternative formulation of tenofovir that may be better tolerated in patients with mild to moderate renal impairment, but its use in patients with severe or end-stage kidney disease is not recommended 4, 8.
Renal Function Monitoring
- Regular monitoring of renal function is essential in patients with CKD, particularly when using antiretroviral medications that may interact with creatinine transporters or have nephrotoxic potential 8, 5.
- Clinicians should be aware of the potential effects of antiretroviral medications on renal function and adjust treatment regimens accordingly to minimize the risk of kidney damage or worsening renal function 4, 7.