What are the treatment recommendations for a patient with HIV and diabetes taking Viread (Tenofovir) and insulin, considering potential kidney function impairment?

Management of HIV and Diabetes in Patients on Viread (Tenofovir) and Insulin

Continue both Viread and insulin with close renal monitoring, but immediately assess kidney function and consider switching from tenofovir disoproxil fumarate to an integrase inhibitor-based regimen if any renal impairment is detected, as tenofovir poses significant nephrotoxicity risk that is compounded by diabetes-related kidney disease. 1, 2, 3

Critical Renal Monitoring Requirements

Baseline and ongoing kidney function assessment is mandatory before and during tenofovir therapy, especially in diabetic patients who have inherently increased nephropathy risk. 1

• Obtain baseline urinalysis and calculated creatinine clearance (using Cockcroft-Gault, not eGFR) before continuing tenofovir 1
• Monitor estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein prior to initiation and periodically during therapy in patients at risk for renal dysfunction 3
• Check for proteinuria of grade ≥1+ by dipstick analysis, as this warrants nephrology referral 1
• Diabetic patients with HIV have 5-fold greater risk of hyperglycemia compared to HIV alone, making renal monitoring even more critical 1

Tenofovir Dosing Adjustments Based on Renal Function

If creatinine clearance falls below 50 mL/min, adjust tenofovir dosing interval immediately or discontinue entirely. 3

• For CrCl 30-49 mL/min: dose every 48 hours 3
• For CrCl 10-29 mL/min: dose every 72-96 hours 3
• For CrCl <10 mL/min or hemodialysis: no reliable dosing recommendations exist; consider alternative antiretroviral 3
• Discontinue tenofovir immediately if acute renal failure, Fanconi syndrome, or severe hypophosphatemia develops 3

Preferred Alternative: Switch to Integrase Inhibitor-Based Regimen

The optimal strategy is to discontinue tenofovir disoproxil fumarate and switch to an integrase inhibitor (dolutegravir, raltegravir, or bictegravir) with abacavir or emtricitabine as the NRTI backbone. 2

• Integrase inhibitors require no dose adjustment in renal failure and have minimal nephrotoxicity 2
• Avoid tenofovir disoproxil fumarate (TDF) entirely in patients with diabetes due to cumulative nephrotoxicity risk 2
• Tenofovir is linked to rapid eGFR decline, incident CKD, and interstitial nephritis 2
• Cases of acute renal failure requiring hospitalization and renal replacement therapy have been reported with TDF 3

Diabetes Management in HIV Patients

Continue insulin therapy and manage diabetes according to American Diabetes Association guidelines, using insulin-sensitizing agents as first-line if oral agents are needed. 1

• Monitor fasting blood glucose at baseline, within 4-6 weeks of starting antiretroviral therapy, and every 3-4 months during the first year 1, 4
• Check hemoglobin A1c every 6 months 4
• Lifestyle modifications (weight loss, increased exercise, dietary modification) should be implemented first 1
• If therapeutic intervention beyond insulin is needed, insulin-sensitizing agents (metformin, thiazolidinediones) are preferred 1

Critical Metformin Warning

If metformin is used for diabetes management, exercise extreme caution due to risk of lactic acidosis when combined with tenofovir. 5

• A case report documented severe lactic acidosis requiring continuous veno-venous hemofiltration after concomitant metformin and tenofovir use 5
• Metformin should be avoided or used with extreme caution if creatinine clearance is impaired 5
• Monitor for symptoms of lactic acidosis: fatigue, nausea, vomiting, abdominal pain, tachypnea 1, 5

Avoid Nephrotoxic Drug Combinations

Never combine tenofovir with other nephrotoxic agents, particularly NSAIDs, as this dramatically increases acute renal failure risk. 3

• Avoid the "triple whammy" combination: NSAIDs + diuretics + ACE inhibitors/ARBs 2
• Cases of acute renal failure requiring hospitalization occurred in HIV patients on tenofovir who started high-dose or multiple NSAIDs 3
• Consider alternatives to NSAIDs for pain management in patients at risk for renal dysfunction 3
• Do not use tenofovir with adefovir (HEPSERA) or other tenofovir-containing products 3

Monitoring for Insulin Abnormalities from HIV Therapy

Be aware that HIV infection itself, independent of antiretroviral therapy, can cause insulin resistance and glucose abnormalities. 1, 6, 7

• HIV-infected patients have increased risk of insulin resistance even when ART-naive 6, 7
• Tenofovir (an NRTI) is associated with insulin resistance, though less than protease inhibitors 1
• Advise patients about warning signs of hyperglycemia: polydipsia, polyphagia, polyuria 1
• Maintain recommended body weight to minimize metabolic complications 1

When to Increase Insulin Monitoring Frequency

Increase glucose monitoring to 3-4 times daily during the first 3-4 weeks after any antiretroviral regimen change. 8

• Patients with chronic kidney disease have impaired insulin clearance and reduced renal gluconeogenesis, increasing both hyper- and hypoglycemia risk 8
• Consider reducing insulin doses by 20% when adding medications that may lower glucose 8
• Document current diabetes medications and recent glycemic control (HbA1c) before any regimen changes 8

Signs of Proximal Renal Tubulopathy Requiring Immediate Evaluation

Persistent bone pain, pain in extremities, fractures, or muscular pain/weakness may indicate Fanconi syndrome from tenofovir and require immediate renal function evaluation. 3

• Tenofovir can cause renal tubular injury with severe hypophosphatemia 3
• Monitor serum phosphorus periodically during therapy 3
• Bone mineral density decreases have been observed with tenofovir 3

Critical Pitfalls to Avoid

• Never continue tenofovir if acute kidney injury develops—switch immediately to integrase inhibitor-based regimen 2, 3
• Never withhold antiretroviral therapy due to renal dysfunction—adjust dosing instead, as discontinuing HAART worsens HIV outcomes 2
• Never rely on eGFR equations in this population—use Cockcroft-Gault creatinine clearance calculation, as certain antiretrovirals (dolutegravir, rilpivirine, ritonavir, cobicistat) alter creatinine measurements 2
• Never use protease inhibitors in patients with significant renal impairment—these are associated with hyperglycemia and require ritonavir/cobicistat boosting that increases nephrotoxicity 1, 2