What first‑line antiretroviral regimen and monitoring plan should be used for an HIV‑positive adult in India with elevated creatinine (impaired renal function), taking into account eGFR thresholds, HLA‑B*5701 status, and necessary dose adjustments?

Treatment Algorithm for HIV-Positive Patients in India with Raised Creatinine

For HIV-positive adults in India with elevated creatinine, avoid tenofovir disoproxil fumarate (TDF) and use an integrase strand transfer inhibitor (InSTI)-based regimen with abacavir/lamivudine as the NRTI backbone after confirming HLA-B*5701 negativity. 1

Initial Assessment and eGFR Stratification

Before initiating ART, calculate creatinine clearance using the Cockcroft-Gault equation—do not rely on serum creatinine alone, as normal values can mask severe renal impairment, especially in elderly or low-muscle-mass patients. 1

Baseline Testing Required:

• HLA-B*5701 screening before abacavir use (mandatory to prevent hypersensitivity reactions) 1
• Estimated glomerular filtration rate (eGFR) or creatinine clearance 1
• Urinalysis for proteinuria, glycosuria, and phosphaturia 1
• Serum phosphate and potassium levels 1
• HIV RNA level and CD4 count 1

Recommended First-Line Regimens Based on Renal Function

For eGFR ≥50 mL/min/1.73 m²:

Preferred regimen: Dolutegravir/abacavir/lamivudine 1

• Abacavir requires no dose adjustment for renal insufficiency, making it the most attractive nucleoside option 1
• Dolutegravir does not require dose adjustment at this eGFR level 1
• Lamivudine requires dose reduction when creatinine clearance falls below 50 mL/min 1

Alternative regimens:

• Raltegravir plus abacavir/lamivudine 1
• Darunavir/cobicistat plus abacavir/lamivudine (high barrier to resistance, useful if adherence concerns) 1

For eGFR 30-49 mL/min/1.73 m²:

Preferred regimen: Dolutegravir plus abacavir with dose-adjusted lamivudine 1

• Lamivudine dose: reduce to 150 mg once daily or 50 mg twice daily 1
• If tenofovir alafenamide (TAF) is available and eGFR >30 mL/min, TAF/emtricitabine can be considered, but abacavir remains safer 1

For eGFR <30 mL/min/1.73 m²:

Preferred regimen: Dolutegravir plus abacavir with further dose-adjusted lamivudine 1

• Lamivudine dose: 150 mg first dose, then 100 mg once daily for eGFR 15-29 mL/min 1
• Avoid TAF when creatinine clearance is below 30 mL/min 1
• Absolutely avoid TDF at this level 1

For End-Stage Renal Disease (ESRD) on Hemodialysis:

Regimen: Elvitegravir/cobicistat/TAF/emtricitabine once daily has supporting data in hemodialysis patients 1

• Alternative: Dolutegravir plus abacavir with lamivudine 25-50 mg once daily (post-dialysis dosing) 1
• Evaluate for kidney transplantation, as HIV-infected patients have high rates of patient and graft survival 1

Critical Drugs to Avoid in Renal Impairment

Tenofovir Disoproxil Fumarate (TDF):

• Avoid or dose-adjust when creatinine clearance <60 mL/min 1
• TDF causes proximal tubular dysfunction in 1-2% of recipients and is associated with eGFR decline, particularly when combined with ritonavir-boosted protease inhibitors 1, 2, 3
• If TDF must be used (e.g., for hepatitis B co-infection), dose every 48 hours for moderate impairment (CrCl 30-49 mL/min) and every 72-96 hours for severe impairment (CrCl 10-29 mL/min) 4
• For ESRD on hemodialysis, dose TDF 300 mg every 7 days after dialysis 4

Cobicistat-Boosted Regimens:

• Darunavir/cobicistat and atazanavir/cobicistat increase tenofovir exposure and nephrotoxicity risk 1
• Cobicistat inhibits tubular creatinine secretion, artificially raising serum creatinine without true GFR decline, but this does not negate real nephrotoxicity risk 1

Atazanavir and Lopinavir/Ritonavir:

• Linked to interstitial nephritis, nephrolithiasis, and rapid eGFR decline 1
• Should be avoided in patients with CKD or at high CKD risk 1

Monitoring Protocol

At ART Initiation or Modification:

• eGFR, urinalysis, serum phosphate, and potassium 1

Follow-Up Monitoring:

• 1-3 months after starting ART: Repeat eGFR and urinalysis 2
• Every 6 months once stable: eGFR and HIV RNA 1
• More frequent monitoring (every 3 months) if baseline eGFR <50 mL/min or risk factors present (hypertension, diabetes, hepatitis B/C co-infection) 1, 2

Red Flags Requiring Immediate Action:

• eGFR decline >25% from baseline AND drops to <60 mL/min 1
• New or worsening proteinuria or albuminuria 1
• Euglycemic glycosuria or hypophosphatemia (suggests proximal tubular dysfunction) 1
• If these occur, discontinue TDF immediately and switch to abacavir-based regimen 1

Special Considerations for India

Hepatitis B Co-Infection:

• Use TDF or TAF (with appropriate dose adjustment) plus lamivudine or emtricitabine 1
• If renal function prohibits tenofovir, use dose-adjusted TDF (safer than omitting hepatitis B treatment) or consider entecavir with close HIV RNA monitoring 1

Tuberculosis Co-Infection:

• Use efavirenz (600 mg daily), raltegravir (800 mg twice daily), or dolutegravir (50 mg twice daily) with 2 NRTIs (excluding TAF due to rifampin interaction) 1
• Abacavir/lamivudine is the preferred NRTI backbone with rifampin-based TB therapy 1

Cost and Availability:

• Generic formulations of dolutegravir, abacavir, and lamivudine are widely available in India 1
• If abacavir is unavailable and HLA-B*5701 testing is not accessible, use dose-adjusted TDF with intensive renal monitoring rather than omitting ART 1, 2

Common Pitfalls to Avoid

1. Do not use TDF at full dose when eGFR <60 mL/min—this is the single most common cause of preventable ART-related nephrotoxicity 1, 2

2. Do not skip HLA-B*5701 testing before abacavir—hypersensitivity reactions can be life-threatening 1

3. Do not combine TDF with ritonavir-boosted protease inhibitors in patients with any renal impairment—this combination has the highest nephrotoxicity risk 1, 3

4. Do not rely on serum creatinine alone—calculate creatinine clearance, especially in elderly or malnourished patients 1, 2

5. Do not forget to dose-adjust lamivudine—it requires reduction when CrCl <50 mL/min 1