Can injectable antiretroviral (ARV) therapy be given to a patient with chronic kidney disease (CKD)?

Injectable Antiretroviral Therapy in Patients with Chronic Kidney Disease

Yes, injectable antiretroviral (ARV) therapy can be given to patients with chronic kidney disease (CKD), but specific dose adjustments and medication selection are required based on the severity of renal impairment.

Injectable ARV Options in CKD

According to the HIV Medicine Association of the Infectious Diseases Society of America guidelines, enfuvirtide, which is administered subcutaneously, requires no dose adjustment in patients with CKD or end-stage renal disease (ESRD) 1.

Specific Injectable ARV Recommendations:

• Enfuvirtide: 90 mg subcutaneous twice daily - No dose adjustment needed with any level of CKD or ESRD 1

Other ARV Classes and Renal Considerations

When managing HIV patients with CKD, the following considerations apply to different ARV classes:

Integrase Strand Transfer Inhibitors (INSTIs)

• Raltegravir: No dose adjustment needed with CKD or ESRD 1
• Dolutegravir:
  • CrCl >30 mL/min: Standard dose
  • CrCl <30 mL/min: Use with close monitoring due to 40% decrease in dolutegravir concentrations 1

CCR5 Antagonists

• Maraviroc:
  • CrCl >30 mL/min: No dose adjustment
  • CrCl <30 mL/min: 300 mg PO twice daily; reduce to 150 mg twice daily if orthostatic hypotension occurs
  • Avoid with CYP3A4 inhibitors in CKD patients 1

Medications to Use with Caution or Avoid

• Tenofovir disoproxil fumarate (TDF): Should be avoided in patients with pre-existing kidney disease when other effective options exist 1

• Tenofovir alafenamide (TAF):

  • Well-tolerated in mild to moderate renal impairment (CrCl >30 mL/min)
  • Not recommended in patients with CrCl <15 mL/min who are not on hemodialysis 2, 3
  • In hemodialysis patients, administer after dialysis 2

• Atazanavir:

  • Avoid unboosted atazanavir in hemodialysis patients
  • Avoid boosted atazanavir in treatment-experienced patients on hemodialysis 1

Benefits of ARV Therapy in CKD Patients

ARV therapy has been associated with:

• Lower incidence of HIV-associated nephropathy (HIVAN)
• Improved kidney function and lower ESRD risk in patients with HIVAN 1
• Slower rate of GFR decline (0.08 vs 4.3 mL/minute/month) in patients with HIVAN 1
• Clinical remissions in HIV-associated thrombotic microangiopathy (TMA) 1

Monitoring Recommendations

For CKD patients on ARV therapy:

• Monitor serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients
• Assess serum phosphorus in patients with CKD
• Monitor for drug-drug interactions, especially with calcineurin inhibitors in transplant recipients
• Closely monitor antiviral efficacy in protease inhibitor treatment-experienced patients 1

Common Pitfalls and Caveats

1. Tenofovir toxicity: Discontinue TDF in patients who develop reduced GFR (>25% from baseline and to <60 mL/minute/1.73 m²), especially with evidence of proximal tubular dysfunction 1

2. Drug interactions: Avoid concurrent use of nephrotoxic medications with potentially nephrotoxic ARVs

3. Monitoring challenges: Some ARVs (NNRTIs, PIs, and INSTIs) can inhibit tubular creatinine secretion, causing stable reductions in creatinine clearance of 5-20 mL/min without actual kidney injury 3

4. Hemodialysis considerations: For patients on hemodialysis, administer dose after hemodialysis on dialysis days 1

5. Progressive decline: In patients with CKD or progressive decline in eGFR, antiretrovirals with nephrotoxic potential should be avoided or discontinued 4

By carefully selecting appropriate ARV medications and monitoring kidney function, patients with CKD can safely receive effective HIV treatment, including injectable options like enfuvirtide when indicated.