Antiretroviral Therapy Selection for HIV Patients with Chronic Liver Disease and Acute Kidney Injury
In an HIV patient with chronic liver disease and acute kidney injury from sepsis, you should initiate integrase inhibitor-based ART with bictegravir/emtricitabine/tenofovir alafenamide (TAF) or dolutegravir plus emtricitabine/TAF, avoiding tenofovir disoproxil fumarate (TDF), protease inhibitors, and NRTIs requiring renal dose adjustment.
Immediate ART Considerations in AKI
Avoid tenofovir disoproxil fumarate (TDF) completely in acute kidney injury, as it causes proximal tubular dysfunction and worsens renal function. 1, 2 The Infectious Diseases Society of America guidelines explicitly state that TDF should be discontinued when GFR drops by >25% and decreases to <60 mL/min/1.73 m² from baseline, particularly with evidence of proximal tubular dysfunction 1. In your patient with AKI from sepsis, TDF is contraindicated.
Switch to tenofovir alafenamide (TAF) instead of TDF, as TAF has significantly less renal toxicity and does not require dose adjustment until severe renal impairment. 1, 3, 2 TAF is the preferred tenofovir formulation in patients with any degree of renal dysfunction 3, 2.
Specific Regimen Recommendations
For patients with CrCl ≥30 mL/min: Use bictegravir/emtricitabine/TAF (Biktarvy) without dose adjustment. 4 This integrase inhibitor-based single-tablet regimen avoids the nephrotoxicity of TDF and the hepatotoxicity concerns of protease inhibitors in your patient with chronic liver disease 4.
For patients with CrCl 15-29 mL/min: Bictegravir is not recommended; use dolutegravir 50 mg daily plus emtricitabine/TAF or abacavir/lamivudine instead. 1, 4 Dolutegravir does not require renal dose adjustment and has minimal hepatic metabolism concerns 1.
NRTIs to Avoid in AKI
Do not use lamivudine, emtricitabine, or abacavir at standard doses without adjustment when CrCl <50 mL/min. 1 Lamivudine requires dose reduction to 150 mg daily when CrCl 30-49 mL/min and 150 mg first dose then 100 mg daily when CrCl 15-29 mL/min 1. Emtricitabine requires reduction to 200 mg every 48 hours when CrCl 30-49 mL/min 1.
Abacavir is the only NRTI not requiring renal dose adjustment, making it attractive for AKI, but requires HLA-B*5701 screening before initiation to prevent hypersensitivity reactions. 1 However, abacavir may increase cardiovascular risk in some studies, which is concerning given that CKD itself increases cardiovascular disease risk 1.
Protease Inhibitors: Avoid in This Context
Avoid ritonavir-boosted protease inhibitors (atazanavir, lopinavir/ritonavir) in patients with AKI, as they increase tenofovir nephrotoxicity risk and can cause interstitial nephritis. 1, 3, 5 The European AIDS Clinical Society specifically recommends avoiding atazanavir and lopinavir/ritonavir in settings of CKD or rapid eGFR decline 3, 5.
Indinavir is absolutely contraindicated in AKI due to crystalluria, nephrolithiasis, and direct tubular toxicity. 1 Risk factors include low lean body mass and concomitant trimethoprim-sulfamethoxazole use 1.
Monitoring Strategy During AKI
Calculate creatinine clearance using Cockcroft-Gault formula rather than eGFR equations, as eGFR requires steady-state creatinine and is inaccurate in AKI. 3 Measure serum creatinine and electrolytes every 12-24 hours during acute management 3.
Monitor for proximal tubular dysfunction markers: euglycemic glycosuria, hypophosphatemia with increased urinary phosphorus excretion, and new-onset or worsening proteinuria. 1 A urinary albumin-to-total protein ratio <0.4 suggests proximal tubular disease rather than glomerular disease 1.
Managing Concurrent Sepsis and Nephrotoxins
Discontinue all nephrotoxic medications immediately: NSAIDs, aminoglycosides, and the "triple whammy" combination (NSAIDs + diuretics + ACE inhibitors/ARBs). 3 This is critical as concurrent nephrotoxic medications dramatically increase AKI risk 3, 6.
For sepsis treatment requiring piperacillin/tazobactam, check renal function before initiation and monitor regularly, as this antibiotic increases AKI risk in CKD patients. 6
Hepatitis Considerations
In patients with chronic hepatitis C and CrCl <30 mL/min, direct-acting antivirals (simeprevir, daclatasvir, ledipasvir, ombitasvir/paritaprevir/ritonavir with dasabuvir) can be used without dose adjustment only if CrCl ≥30 mL/min. 1 Below this threshold, safety and efficacy data are lacking 1.
For hepatitis B coinfection requiring treatment, dose-adjusted TDF or TAF can be considered, but TAF is strongly preferred given the AKI. 1 Entecavir is an alternative for hepatitis B that does not treat HIV 1.
Common Pitfalls to Avoid
Never use standard-dose NRTIs without renal adjustment in AKI, as this causes severe bone marrow suppression and worsening toxicity. 3 Fixed-dose combinations like Combivir (zidovudine/lamivudine) or Trizivir (zidovudine/lamivudine/abacavir) should be administered as separate component medications when CrCl <50 mL/min 1.
Do not withhold ART simply because of severe renal dysfunction. 1 The Infectious Diseases Society of America explicitly states that HAART should not be withheld from patients because of renal dysfunction severity 1.
Avoid calcium channel blockers for blood pressure control in patients on protease inhibitors due to drug interactions. 1, 5 Use ACE inhibitors or ARBs preferentially for proteinuria, but monitor closely in AKI 1.
Prognosis and Long-Term Planning
AKI in HIV patients is independently associated with increased in-hospital mortality, and even with complete recovery, patients remain at increased risk of progressive CKD requiring long-term follow-up. 3 Early vascular access planning and consideration of kidney transplantation should begin if CKD progresses 5.