What is the best approach for managing HIV in a patient with Chronic Liver Disease (CLD) and Acute Kidney Injury (AKI) due to sepsis, with Impaired renal function?

HIV Treatment in CLD Patients with AKI (Creatinine 5.3) Due to Sepsis

Continue HIV antiretroviral therapy (ART) immediately with renally-adjusted dosing, as HAART should not be withheld from patients simply because of severe renal dysfunction, and discontinue all nephrotoxic antiretrovirals immediately. 1

Immediate Antiretroviral Adjustments

Discontinue nephrotoxic agents immediately:

• Stop tenofovir disoproxil fumarate (TDF) immediately if currently prescribed, as it causes proximal tubular injury and Fanconi syndrome, and is contraindicated when creatinine clearance is severely reduced 1, 2
• Discontinue atazanavir and lopinavir/ritonavir, as these protease inhibitors are linked to rapid eGFR decline, incident CKD, and interstitial nephritis 1, 3
• Avoid indinavir due to crystalluria and progressive renal dysfunction 1

Switch to renal-safe ART regimen:

• Use integrase inhibitors (dolutegravir, raltegravir, or bictegravir) as the preferred anchor agents, as these do not require dose adjustment in renal failure and have minimal nephrotoxicity 1
• Select abacavir or emtricitabine as NRTI backbone options, avoiding TDF entirely 1, 3
• If tenofovir is absolutely required, use tenofovir alafenamide (TAF) instead of TDF, though even TAF requires caution with severe renal impairment 3

Dose Adjustments for Severe Renal Impairment

With creatinine 5.3 mg/dL (estimated CrCl <15 mL/min):

• Emtricitabine: reduce to 200 mg every 96 hours or 133 mg every 24 hours 1
• Lamivudine: reduce to 50 mg once daily or 150 mg first dose, then 50 mg once daily 1
• Integrase inhibitors (dolutegravir, bictegravir): no dose adjustment required 1
• Avoid all protease inhibitors that require ritonavir or cobicistat boosting due to drug-drug interactions and nephrotoxicity 1

Management of Sepsis-Related AKI

Treat the underlying sepsis aggressively:

• Sepsis is the most common cause of AKI in HIV patients (59% of cases) and is independently associated with 23-fold increased odds of AKI 4, 5
• Initiate early goal-directed resuscitation with isotonic crystalloids, avoiding starch-containing fluids which are nephrotoxic 5
• Use norepinephrine as first-line vasopressor, as it is the dominant agent with the best renal outcomes in septic AKI 5

Discontinue all additional nephrotoxic medications:

• Stop NSAIDs immediately, as high-dose or multiple NSAIDs cause acute renal failure in HIV patients with risk factors for renal dysfunction 2
• Discontinue aminoglycosides if being used for sepsis treatment 3
• Avoid the "triple whammy" combination (NSAIDs + diuretics + ACE inhibitors/ARBs) 3

Hepatorenal Syndrome Considerations in CLD

If hepatorenal syndrome (HRS-AKI) is contributing:

• Administer terlipressin 0.5-1 mg IV every 4-6 hours (or 2-12 mg/24h continuous infusion) plus albumin 20-40 g/day, as this is the most effective treatment for HRS with response rates of 64-76% 1
• Norepinephrine via central line is an acceptable alternative if terlipressin is unavailable 1
• Ensure diagnosis meets HRS-AKI criteria: cirrhosis with ascites, Stage 2-3 AKI, no response to volume expansion with albumin 1 g/kg (max 100 g/day) for 2 consecutive days, absence of shock, no nephrotoxic drugs, and absence of parenchymal kidney disease 1

Monitoring Strategy

Intensive monitoring during acute phase:

• Measure serum creatinine and electrolytes every 12-24 hours during the first 48-72 hours 3
• Calculate creatinine clearance using Cockcroft-Gault formula rather than eGFR equations, as eGFR equations are inaccurate in AKI 3
• Monitor for signs of proximal renal tubulopathy: persistent bone pain, pain in extremities, fractures, muscular weakness, glycosuria, and hypophosphatemia 2
• Check urine protein:creatinine ratio and urinalysis to differentiate functional versus structural AKI 1

Be aware that certain antiretrovirals alter creatinine measurements:

• Dolutegravir, rilpivirine, ritonavir, and cobicistat reduce calculated creatinine clearance by 5-20 mL/min by blocking tubular creatinine secretion without actual GFR decline 1
• This artificial elevation should be taken into account when interpreting renal function 1

Renal Replacement Therapy Considerations

Indications for RRT in this patient:

• With creatinine 5.3 mg/dL and sepsis, consider RRT if there is fluid overload, severe acidosis, hyperkalemia, or uremic symptoms 1
• Dialysis should not be withheld solely because of HIV infection, as HIV patients on HAART achieve survival rates comparable to non-HIV dialysis patients 1, 6
• Prognosis with RRT in cirrhotic patients with AKI is poor unless duration is short and integrated into a therapeutic plan such as liver transplantation 1

Critical Pitfalls to Avoid

Common errors that worsen outcomes:

• Never continue TDF in severe AKI, as cases of acute renal failure requiring hospitalization and renal replacement therapy have been reported 2
• Do not use calcium channel blockers with protease inhibitors due to drug interactions causing hypotension and conduction delays 1
• Avoid withholding HAART due to renal dysfunction severity, as this worsens HIV outcomes and immune function 1
• Do not rely on single creatinine values; use creatinine trajectories to identify progressive decline 1

Prognosis and Recovery

Expected outcomes:

• AKI in HIV patients carries 27.3% in-hospital mortality versus 8% without AKI 4
• Among HIV patients with Stage 3 AKI in ICU, only 41% are alive 90 days after admission 7
• If sepsis resolves, 74% of survivors regain good renal function, though some remain RRT-dependent or have significant ongoing dysfunction 7
• Even with complete AKI recovery, patients remain at increased risk of progressive CKD and require long-term nephrology follow-up 3