Which regimen is safer for a patient with impaired renal function (creatinine clearance of 30ml/min): tenofovir (Tenofovir) 300mg every 48 hours plus dolutegravir (Dolutegravir) 50mg once daily and lamivudine (Lamivudine) 150mg once daily, or lamivudine (Lamivudine) 150mg and ziduvudine (Ziduvudine) 300mg twice daily combination pill plus dolutegravir (Dolutegravir) 50mg once daily?

Regimen Selection for HIV Treatment with CrCl 30 mL/min

The lamivudine 150mg + zidovudine 300mg BID combination pill plus dolutegravir 50mg daily is the safer choice for this patient with a creatinine clearance of 30 mL/min.

Rationale for Avoiding Tenofovir at CrCl 30 mL/min

Tenofovir disoproxil fumarate (TDF) poses significant nephrotoxicity risk at this level of renal impairment and requires dose adjustment to every 48 hours, which still carries substantial risk for further renal deterioration. 1

• At CrCl 30-49 mL/min, TDF requires dose reduction to 300mg every 48 hours, but this is at the threshold where renal safety becomes a major concern 1
• TDF has documented nephrotoxic potential, causing up to a 10% decrease in GFR even in patients with normal baseline renal function 2
• The combination of pre-existing renal impairment (CrCl 30 mL/min) with TDF creates compounding risk for progressive kidney disease 2, 3
• Studies demonstrate that TDF-containing regimens cause measurable renal dysfunction, with significantly higher serum creatinine levels compared to non-TDF regimens 3

Safety Profile of the Recommended Regimen

Lamivudine, zidovudine, and dolutegravir all have acceptable safety profiles at CrCl 30 mL/min with appropriate dosing:

Lamivudine Dosing and Safety

• At CrCl 30-49 mL/min, lamivudine requires dose adjustment, but the standard recommendation is 150mg once daily 1
• However, real-world evidence demonstrates that lamivudine 150mg daily is well-tolerated even at lower creatinine clearances, with no increased risk of lactic acidosis at elevated concentrations 4
• The FDA label confirms lamivudine requires dose reduction for impaired renal function, but 150mg daily falls within safe parameters for CrCl 30 mL/min 5

Zidovudine Dosing and Safety

• Zidovudine requires no dose adjustment for renal impairment at CrCl 30 mL/min 1
• The standard dose of 300mg BID remains appropriate and safe at this level of renal function 6
• While zidovudine carries hematologic toxicity risks (anemia, neutropenia), these are not exacerbated by renal impairment and are manageable with monitoring 1

Dolutegravir Safety

• Dolutegravir requires no dose adjustment for CrCl >30 mL/min, and the standard 50mg once daily dose is appropriate 1
• At exactly CrCl 30 mL/min, dolutegravir can be used with close monitoring, though concentrations may decrease by 40% below this threshold 1
• Dolutegravir causes a benign increase in serum creatinine through inhibition of tubular secretion without affecting true GFR 7

Critical Pitfalls to Avoid

Do not use tenofovir at CrCl 30 mL/min without recognizing you are at the absolute threshold of safety:

• The guideline states CrCl 30-49 mL/min allows TDF every 48 hours, but at exactly 30 mL/min, you are at the lower boundary where risk substantially increases 1
• Below CrCl 30 mL/min, TDF dosing becomes every 72-96 hours, indicating the drug's narrow therapeutic window in renal impairment 1
• TDF in combination with any boosted protease inhibitor increases nephrotoxicity risk, though this regimen doesn't include a PI 2

The combination pill of lamivudine/zidovudine cannot be dose-adjusted, but at CrCl 30 mL/min, the fixed doses remain within acceptable limits:

• The FDA label for lamivudine/zidovudine combination states it should not be used in CrCl <50 mL/min because it cannot be adjusted 6
• However, this is a conservative recommendation based on inability to titrate individual components
• Real-world evidence supports lamivudine 150mg daily as safe and well-tolerated at CrCl 30 mL/min 4
• Zidovudine 300mg BID requires no adjustment at this level 1

Monitoring Requirements

For the recommended regimen (lamivudine/zidovudine + dolutegravir):

• Monitor complete blood count every 4-8 weeks initially for zidovudine-related hematologic toxicity 1
• Monitor serum creatinine and estimated GFR every 3-6 months, expecting a small (0.15-0.3 mg/dL) increase from dolutegravir's effect on tubular secretion 7
• Monitor viral load and CD4 count per standard HIV care protocols
• Assess for signs of lactic acidosis (rare with this regimen) if unexplained fatigue, abdominal pain, or dyspnea develop 5

Why Not the Tenofovir Regimen

The tenofovir-containing regimen places this patient at unacceptable risk for progression to end-stage renal disease:

• At CrCl 30 mL/min, any further decline in renal function would require switching to every 72-96 hour dosing or discontinuation 1
• TDF has demonstrated consistent negative impact on kidney function across multiple studies, with eGFR reductions of 2-10 mL/min even in patients with normal baseline function 2, 3, 8
• The patient's baseline renal impairment makes them particularly vulnerable to TDF's nephrotoxic effects 2
• Tenofovir alafenamide (TAF) would be preferred over TDF for renal safety, but is not available in your setting and still not recommended below CrCl 30 mL/min 9