What is the Glomerular Filtration Rate (GFR) cutoff for initiating Descovy (emtricitabine and tenofovir alafenamide) therapy in patients with HIV-1 infection and impaired renal function?

Descovy GFR Cutoff for Initiation

Descovy (emtricitabine/tenofovir alafenamide) should not be initiated in patients with creatinine clearance below 30 mL/min, as tenofovir alafenamide is not recommended below this threshold. 1, 2

Specific GFR Thresholds

For Tenofovir Alafenamide (TAF) Component

• TAF is not recommended when creatinine clearance is <30 mL/min according to FDA labeling and international guidelines 1, 2
• TAF can be safely used without dose adjustment when creatinine clearance is ≥30 mL/min 2
• The 30 mL/min cutoff represents the lower safety boundary established through pharmacokinetic studies in patients with severe renal impairment 3

For Emtricitabine Component

• Emtricitabine requires dose adjustment (not contraindication) at creatinine clearance <50 mL/min 4
• At creatinine clearance 30-49 mL/min: dose every 48 hours 4
• At creatinine clearance 15-29 mL/min: dose every 72 hours 4
• At creatinine clearance <15 mL/min or on hemodialysis: dose every 96 hours 4

Clinical Context and Monitoring

Pre-Initiation Assessment

• Baseline urinalysis and calculated creatinine clearance must be obtained before initiating Descovy, particularly in Black patients, those with advanced HIV disease, or those with comorbid conditions due to increased nephropathy risk 1, 5
• Use the Cockcroft-Gault equation for creatinine clearance calculation, as medication dosing studies have traditionally used this method 1

Advantages of TAF Over TDF

• TAF demonstrates superior renal safety compared to tenofovir disoproxil fumarate (TDF), with significantly less eGFR decline 6
• In clinical trials, TAF caused eGFR decline of only 0.6-1.8 mL/min compared to 4.8-5.4 mL/min with TDF 6
• TAF is preferred over TDF for patients with existing renal impairment or CKD risk factors 6

High-Risk Populations Requiring Enhanced Monitoring

• Female patients, African American ethnicity, and CD4 nadir <200 cells/mm³ are at higher risk for renal dysfunction 7, 5
• Patients with diabetes, hypertension, or hepatitis C coinfection require annual screening for proteinuria 1
• Concomitant use with ritonavir-boosted protease inhibitors or cobicistat increases tenofovir exposure and nephrotoxicity risk 1, 8

Important Caveats

Avoid Specific Drug Combinations

• Do not use Descovy with rifamycin drugs, as neither TAF nor cobicistat-boosted regimens are recommended with rifamycins 1
• Ritonavir-boosted protease inhibitors and cobicistat significantly increase tenofovir exposure and should be avoided or carefully monitored 1, 8

Ongoing Monitoring Requirements

• Monitor eGFR, urinalysis, and test for glycosuria and proteinuria every 6 months once HIV RNA is stable 1
• Discontinue TAF if renal function worsens, particularly with evidence of proximal tubular dysfunction 1, 8
• Patients with eGFR decline >25% from baseline or rapid decline (>3-5 mL/min/1.73 m² per year) should be switched to alternative agents 1, 6