What labs should be checked in a patient with dark urine when initiating Human Immunodeficiency Virus (HIV) medication?

Laboratory Evaluation for Dark Urine in HIV Patients Initiating Antiretroviral Therapy

In a patient with dark urine when initiating HIV medication, immediately obtain a complete blood count with peripheral smear to evaluate for hemolysis (particularly if using oxidant drugs in patients at risk for G6PD deficiency), urinalysis with microscopy, comprehensive metabolic panel with calculated creatinine clearance, liver function tests, and G6PD screening if the patient has predisposing racial or ethnic background. 1, 2

Immediate Priority Labs for Dark Urine

Hemolysis Evaluation

• Complete blood count (CBC) with differential and peripheral blood smear to assess for hemolytic anemia, which can cause dark urine and is life-threatening with certain G6PD variants 1, 3
• G6PD deficiency screening is mandatory before initiating oxidant drugs (dapsone, primaquine, sulfonamides) in patients of African, Mediterranean, Indian, or Southeast Asian descent 1
  • The GdA− variant (10-15% of Black patients) causes milder hemolysis, while Gdmed variant (Mediterranean, Indian, Southeast Asian) can cause life-threatening hemolysis 1
• Lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, and reticulocyte count if hemolysis is suspected 3

Renal Function Assessment

• Urinalysis with microscopy to evaluate for hematuria, proteinuria, glycosuria, and cellular casts 1
  • Dark urine may represent concentrated urine, hematuria, hemoglobinuria, myoglobinuria, or bilirubinuria 4
• Comprehensive metabolic panel including serum creatinine with calculated creatinine clearance using Cockcroft-Gault equation (preferred for medication dosing) 1
• Serum phosphorus if chronic kidney disease is present or suspected, as HIV-associated nephropathy and tenofovir can cause Fanconi syndrome 1, 2
• Urine protein-to-creatinine ratio or albumin-to-creatinine ratio for quantification if dipstick shows proteinuria 1, 5

Hepatic Function

• Liver function tests (AST, ALT, alkaline phosphatase, total and direct bilirubin) to assess for hepatotoxicity or cholestasis that could cause dark urine 1
  • Dark urine with elevated direct bilirubin suggests cholestasis or hepatocellular injury 4

Standard Baseline Labs for HIV Medication Initiation

Core HIV Monitoring

• CD4 cell count with percentage to assess immune status and guide opportunistic infection prophylaxis 1
• Quantitative HIV RNA (viral load) to establish baseline and monitor treatment response 1
• HIV genotype resistance testing (reverse transcriptase and protease) before initiating therapy 1

Additional Required Testing

• Fasting lipid profile as antiretroviral drugs and HIV infection increase cholesterol and triglyceride levels 1
• Fasting glucose or hemoglobin A1c to screen for glucose intolerance and diabetes 1
• HLA-B*5701 testing if abacavir is being considered, as positive patients are at high risk for hypersensitivity reaction 1
• Hepatitis A, B, and C serologies to assess for coinfection 1
• Tuberculosis screening with either tuberculin skin test or interferon-gamma release assay 1
• Sexually transmitted infection screening including syphilis and 3-site nucleic acid amplification testing for chlamydia and gonorrhea 1
• Pregnancy test in persons of childbearing potential 1

Special Considerations for Nephrotoxic Antiretrovirals

Tenofovir Disoproxil Fumarate (TDF) Monitoring

• Baseline and ongoing monitoring of serum creatinine, calculated creatinine clearance, urine glucose, and urine protein is required before and during TDF use 2, 5
• Monthly monitoring for first 3 months, then quarterly thereafter, especially in patients with risk factors for nephropathy 5, 6
• Serum phosphorus should be monitored as TDF can cause proximal tubular dysfunction and Fanconi syndrome 1, 2, 7
• Avoid TDF in patients with creatinine clearance <60 mL/min without dose adjustment 2

High-Risk Populations Requiring Enhanced Monitoring

• Black HIV-infected patients have increased risk of HIV-associated nephropathy and require baseline urinalysis and creatinine clearance 1
• Patients with CD4 count <200 cells/μL or advanced disease are at higher risk for nephropathy 1
• Patients with comorbidities (diabetes, hypertension, hepatitis C coinfection) require more intensive renal monitoring 1, 6
• Patients on concurrent nephrotoxic drugs should have TDF avoided or used with extreme caution 2

Critical Pitfalls to Avoid

• Do not delay ART initiation while waiting for laboratory results unless there is clinical instability; draw all labs before first dose and adjust regimen as needed when results return 1
• Do not use creatinine-based eGFR alone when monitoring patients on rilpivirine, dolutegravir, or cobicistat, as these drugs inhibit tubular secretion of creatinine without true renal impairment 7, 5
• Do not miss G6PD screening in at-risk populations before prescribing oxidant drugs, as life-threatening hemolysis can occur with Gdmed variant 1
• Do not ignore proteinuria even when eGFR is >60 mL/min, as 30% of HIV patients with normal eGFR have abnormal urine protein ratios 6
• If CD4 count <100 cells/μL, obtain serum cryptococcal antigen testing even without meningeal symptoms 1