What antiretroviral therapy regimen is recommended for an HIV‑positive patient with impaired renal function (elevated serum creatinine), taking into account HLA‑B*5701 status and eGFR?

ART Regimen for HIV Patients with Elevated Creatinine

For HIV patients with renal impairment (elevated creatinine), use dolutegravir/lamivudine as the preferred regimen, or bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) if a three-drug regimen is needed.

Primary Recommendation: Dolutegravir/Lamivudine

This two-drug regimen is ideal for renal impairment because:

• Dolutegravir requires no dose adjustment regardless of eGFR level
• Lamivudine is renally cleared but easily dose-adjusted based on creatinine clearance
• Demonstrated robust viral efficacy in ESKD patients with 99% achieving HIV RNA <200 copies/mL 1
• Single-tablet formulation available (dolutegravir 50mg/lamivudine 300mg) that can be used across the eGFR spectrum 1

Important Caveats Before Using Dolutegravir/Lamivudine

You must exclude these contraindications 2:

• HIV RNA >500,000 copies/mL (not studied in GEMINI trials)
• Hepatitis B co-infection (lamivudine monotherapy risks HBV resistance)
• Resistance to either drug (requires genotypic testing before initiation—do not start same day as diagnosis)
• CD4 count <200/μL (lower response rates observed: 79% vs 93% with three-drug regimens)
• HLA-B*5701 positive if considering abacavir alternatives

Lamivudine Dosing in Renal Impairment

Recent evidence challenges traditional dose reductions 1:

• Full-dose lamivudine (300mg daily) was well-tolerated in 32% of patients with eGFR <30 mL/min/1.73m²
• Higher than recommended doses were used in 77% of ESKD patients without toxicity
• Fixed-dose combination (dolutegravir/lamivudine 300mg) merits consideration even in advanced renal disease to avoid under-exposure

Alternative: Bictegravir/Emtricitabine/Tenofovir Alafenamide

If a three-drug regimen is preferred or dolutegravir/lamivudine is contraindicated:

• B/F/TAF maintains stable renal function in mild-to-moderate renal impairment over 240 weeks 3
• Renal adverse events are infrequent and discontinuation due to renal toxicity is rare 3
• TAF is superior to TDF in patients with renal impairment—TAF causes less proximal renal tubular toxicity and bone mineral density loss 2

Why TAF Over TDF in Renal Impairment

The guideline clearly states 2:

• TAF-containing regimens have fewer tenofovir-associated adverse effects including proximal renal tubular toxicity
• TDF increases risk of renal impairment, particularly with BMI <18.5 kg/m² and abnormal baseline eGFR 4
• TDF is associated with 20% incidence of nephrotoxicity in some populations, occurring as early as 24 weeks 4

Regimens to Avoid

Do NOT use:

• Tenofovir disoproxil fumarate (TDF) in patients with existing renal impairment
• Cobicistat-boosted regimens (increases drug interactions and tenofovir levels, worsening renal toxicity) 2
• Abacavir (requires HLA-B*5701 testing, lingering MI concerns, and now superseded by dolutegravir/lamivudine) 2

Monitoring Strategy

• Baseline eGFR is a critical predictor of further renal decline 4
• All HIV patients on HAART show statistically significant decline in renal function over 2 years, regardless of regimen (mean eGFR decrease: 12.4 mL/min/1.73m² with tenofovir, 9 mL/min/1.73m² without) 5
• Combined creatinine + cystatin C-based eGFR equations have the best diagnostic performance (AUC=0.91) for detecting CKD in HIV patients 6

Clinical Algorithm

1. Check HLA-B*5701, hepatitis B status, HIV RNA level, CD4 count, and resistance testing
2. If eGFR <60 mL/min/1.73m² and no contraindications exist: Start dolutegravir/lamivudine
3. If CD4 <200/μL or HIV RNA >500,000 copies/mL: Use B/F/TAF instead
4. If eGFR <30 mL/min/1.73m²: Consider full-dose dolutegravir/lamivudine (300mg) fixed-dose combination based on emerging evidence 1
5. Avoid TDF-containing regimens and cobicistat-boosted regimens entirely