Table 2.

Key clinical pharmacologic aspects of commonly used antiretroviral agents

DrugElimination/t1/2Plasma Protein BindingMetabolismDose in CKD and DialysisNephrotoxicity Potential
Reverse transcription inhibitors
 Abacavir85% by the kidney50%Glucuronidation (36%)No dose adjustmentAcute interstitial nephritis
t1/2 1.5 h for the parent drug and 21 h for the active moietyAlcohol dehydrogenase (30%)
 LamivudinePrimarily by the kidney via organic cation transporter secretionLow <36%Minor, only 5% of drugDose adjustment for Cr. Cl. <50 ml/min, reduce both first and maintenance dose on dialysisRare
t1/2 5–7 hNo significant clearance by HD or CAPD/APD
 Emtricitabine86% by the kidneyLow <4%No significant metabolismDose adjustment for Cr. Cl. <50 ml/minRare
t1/2 8–10 h
 Tenofovir disoproxil fumarate70%−80% by the kidney<7%Hydrolysis (by non-CYP enzymes) intracellularly to tenofovirDose adjustment for Cr. Cl. <50 ml/minAcute kidney disease and CKD, Fanconi syndrome, nephrogenic diabetes insipidus
t1/2 14–17 h300 mg every 48 h for Cr. Cl. 30–50 ml/min, twice weekly for 10–29 ml/min, once weekly on dialysis
Guidelines do not recommend using with eGFR<60 if possible
10% of the administered 300 mg tenofovir disoproxil fumarate dose is removed by 4 h of dialysis
 Tenofovir alafenamide fumarate1% excreted in the urine and 31.7% excreted in feces80%>80 is metabolized intracellularly with Cathepsin Ab in PBMCs and CES1 in hepatocytesNone for Cr. Cl. >30 ml/minProximal tubular cell injury has been reported
t1/2 90 minCYP3A (minimal)Not recommended for Cr. Cl. <30 ml/min
Integrase strand transfer inhibitors
 Raltegravir9% unchanged by the kidney, the rest are metabolites recovered in feces (50%) and urine83%UGT1A1No dose adjustmentRare
t1/2 approximately 9 hNo data on dialysis clearance
 Elvitegravir95% is recovered in feces (hepatobiliary excretion)>99%CYP3A4 (major); UGT1A1/3 (minor)No dose adjustmentRare
t1/2 approximately 3 hNo data on dialysis clearance, but it is unlikely to be dialyzable
t1/2 approximately 9 h when boosted with ritonavir or cobicistat
 Dolutegravir53% is excreted unchanged in feces, <1% by urine, 31% of metabolites in urine>99%UGT1A1 (major)No dose adjustment, not removed by dialysisRare
t1/2 11–12 hCYP3A (minor)
Pharmacoenhancers
 Cobicistat86% excreted in feces, 8% in urine98%CYP3A (major) CYP2D6 (minor)Avoid elvitegravir/cobicistat/tenofovir disoproxil fumarate when Cr. Cl. <70 ml/minRare
t1/2 3–4 hAvoid elvitegravir/cobicistat/tenofovir alafenamide fumarate when Cr. Cl. <30 ml/min
 Ritonavir86% in feces98%–99%CYP3A (major) CYP2D6 (minor)No dose adjustmentAKI, CKD, increased risk of tenofovir disoproxil fumarate nephrotoxicity
t1/2 3–5 h
  • Cr. Cl., creatinine clearance; HD, hemodialysis; CAPD, continuous ambulatory peritoneal dialysis; APD, automated peritoneal dialysis; CYP, cytochrome P; CES1, carboxylesterase 1; UGT, uridine glucuronosyl transferase; PBMCs, peripheral blood mononuclear cells.