What is the first-line treatment for an HIV patient with impaired renal function on dialysis?

First-Line Antiretroviral Therapy for HIV Patients on Dialysis

For HIV patients on dialysis, integrase strand transfer inhibitors (INSTIs) such as raltegravir or dolutegravir combined with appropriate nucleoside reverse transcriptase inhibitors (NRTIs) are the recommended first-line treatment options due to their favorable safety profile and minimal need for dose adjustment in end-stage renal disease (ESRD). 1

Recommended Antiretroviral Regimens for Dialysis Patients

INSTI-Based Regimens (Preferred)

1. Raltegravir-based regimen

   • Raltegravir 400 mg PO twice daily (no dose adjustment needed) 1
   • Plus appropriate NRTI backbone with renal dose adjustments

2. Dolutegravir-based regimen

   • Dolutegravir 50 mg once daily 1
   • Requires close monitoring in patients with CrCl <30 mL/min due to 40% decrease in dolutegravir concentrations
   • May need twice daily dosing (50 mg) in INSTI-experienced patients with certain INSTI mutations

Alternative Regimens

1. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)

   • Emerging data supports use in hemodialysis patients 2
   • Maintains virologic suppression and simplifies treatment to a single tablet once daily
   • Recent studies show adequate drug levels despite lower trough concentrations compared to patients with normal renal function

2. Entry inhibitor option

   • Enfuvirtide 90 mg subcutaneous twice daily (no dose adjustment needed) 1, 3
   • Useful in highly treatment-experienced patients

3. CCR5 antagonist option

   • Maraviroc 300 mg PO twice daily (CrCl <30 mL/min) 1
   • Reduce to 150 mg twice daily if orthostatic hypotension occurs
   • Avoid with CYP3A4 inhibitors in dialysis patients

Medications to Avoid or Use with Caution

1. Avoid or use with caution:

   • Tenofovir disoproxil fumarate (TDF) - avoid in patients with pre-existing kidney disease 1, 3
   • Elvitegravir/cobicistat/tenofovir/emtricitabine (Stribild) - discontinue if CrCl <50 mL/min 1
   • Unboosted atazanavir in hemodialysis patients 1, 4
   • Ritonavir-boosted atazanavir in ART-experienced hemodialysis patients 1, 4

2. Protease inhibitors:

   • If used, monitor antiviral efficacy closely in protease inhibitor treatment-experienced patients 1
   • Reduced trough concentrations have been reported with lopinavir/ritonavir in hemodialysis patients

Dose Adjustments for Common NRTIs in Dialysis

1. Lamivudine:

   • CrCl <15 mL/min: 50 mg first dose, then 25 mg once daily 1
   • Hemodialysis: 50 mg first dose, then 25 mg once daily (administer after dialysis on dialysis days)

2. Emtricitabine:

   • CrCl <15 mL/min: 200 mg every 96 hours 1
   • Hemodialysis: 200 mg every 24 hours (administer after dialysis on dialysis days)

3. Abacavir:

   • No dose adjustment needed for any level of renal impairment 1

Clinical Benefits of ART in Dialysis Patients

• ART has been associated with improved outcomes in HIV patients with kidney disease:
  • Longer time to ESRD (18.4 vs 3.9 months) 1
  • Higher overall renal survival (18.1% vs 12.5%) 1
  • Slower rate of GFR decline in patients with HIV-associated nephropathy (HIVAN) 1, 3
  • Clinical remissions in HIV-associated thrombotic microangiopathy 1, 3

Monitoring Recommendations

1. Regular monitoring:

   • Viral load and CD4 count
   • Serum creatinine and estimated GFR
   • Urine protein and glucose (if residual renal function exists)
   • Serum phosphorus 3

2. Drug-specific monitoring:

   • For dolutegravir: Monitor for virologic breakthrough, especially in INSTI-experienced patients 1
   • For protease inhibitors: Monitor drug levels if available, particularly in treatment-experienced patients 1

Important Clinical Considerations

• Administer dose-adjusted medications after hemodialysis on dialysis days 1, 3
• Consider drug-drug interactions, especially with medications commonly used in ESRD patients
• Monitor for immune reconstitution inflammatory syndrome (IRIS), which may manifest as worsening kidney function after ART initiation
• HIV patients with ESRD should be evaluated for kidney transplantation when clinically stable 1

By following these recommendations, HIV patients on dialysis can achieve viral suppression while minimizing medication-related complications and optimizing outcomes.