A Kidney Number That Rules Out the Easy Answer
His declining kidney function makes his current regimen a poor long-term fit — but each realistic alternative carries a different organ-specific risk of its own, and neither is clearly the safer trade.
E.T., a 67-year-old man, retired four years ago after running his own accounting practice for over three decades, and now spends most weekday mornings in his garden and most Sunday afternoons with his grandson, who has taken to calling him the family's unofficial tax expert whenever anyone needs help sorting paperwork. He has been on a tenofovir disoproxil fumarate-based regimen for over fifteen years, virologically suppressed the entire time, and has managed hypertension with lisinopril for the past decade. His father died of a myocardial infarction at 61, a fact that has stayed present in his own sense of his cardiovascular risk even though his own lipid panel and blood pressure have both been reasonably well controlled. He has no history of kidney stones or urologic disease, and this is the first time in his fifteen years of care that his renal function has drawn specific attention rather than a routine mention.
His renal function has declined steadily over the past year — eGFR down from 52 mL/min to 38, a real, non-trivial trajectory rather than a single abnormal value. Tenofovir disoproxil fumarate is renally cleared and has a well-documented association with proximal tubular injury over long-term use, making his current regimen a genuinely poor long-term fit at this trajectory. Tenofovir alafenamide, the newer prodrug formulation, achieves comparable viral suppression at roughly a tenth the circulating tenofovir concentration and has shown less renal and bone toxicity in direct comparison — but its own label advises against initiation, and caution with continued use, once eGFR falls below 30, a threshold his current trajectory could plausibly reach within one to two years. The alternative, an abacavir-based regimen, sidesteps the tenofovir question entirely, provided his HLA-B*5701 testing — not yet drawn — comes back negative, but carries its own separate cardiovascular signal from the D:A:D cohort study, one concentrated in patients who look a good deal like him — a hypertensive man in his sixties with a strong family history, exactly the profile that signal was strongest in.
HIV clinic, annual renal function review
Tenofovir alafenamide is the most direct substitution here — comparable potency at a tenth the circulating tenofovir concentration, with real trial evidence of less renal and bone toxicity than the disoproxil formulation he's on now. It keeps the rest of his regimen unchanged. I'd switch him to it.
The renal-safety comparison to disoproxil tenofovir is real, and I'm not questioning that part.
But his eGFR has fallen fourteen points in a single year, and alafenamide's own label advises against initiating it below an eGFR of 30 and using caution even approaching it. At his current trajectory, we could plausibly be back here in eighteen months needing to switch again anyway. I'd rather move him off tenofovir entirely now, to an abacavir-based regimen once his HLA-B*5701 comes back negative, than choose a bridge that may not hold for long.
Abacavir isn't a clean substitution either, though. The D:A:D cohort study found increased cardiovascular event risk with abacavir, concentrated specifically in patients with existing cardiovascular risk factors — and he has hypertension and a father who died of an MI at 61. I'll note his other numbers are actually reassuring on that same axis: his LDL is 118 and at goal without any lipid therapy, and his blood pressure is reasonably controlled on lisinopril. He isn't walking into this with every modifiable risk factor left unaddressed — but a controlled risk factor is not the same as an absent one, and D:A:D's signal was seen in patients who had risk factors present, controlled or not. I'm not arguing against the nephrologist's renal-trajectory point, which is real. I'm saying this isn't a renal-safe option versus a renal-risky one — it's two different organ systems each carrying a real signal, and the decision needs to weigh both explicitly rather than treat the kidney number as automatically decisive.
Agreed: HLA-B*5701 testing ordered today, with a switch to abacavir/lamivudine planned pending a negative result, dolutegravir continued unchanged as the backbone partner. His blood pressure and lipid management will be reviewed at the same visit the switch takes effect, addressing the pharmacologist's cardiovascular concern directly rather than leaving it unaddressed once the renal question is resolved.