A Failed Cure: Choosing a Retreatment Regimen After First-Line DAA Failure
A patient's hepatitis C did not clear after first-line direct-acting antiviral therapy. The retreatment regimen is not seriously in dispute. Whether resistance testing is worth sending, and whether anyone has actually asked about adherence, are.
Roberto C., a 48-year-old man, drives a regional delivery route that keeps him on the road four to five days a week, sleeping in his cab more nights than he'd like to admit to his hepatologist. He was diagnosed with chronic hepatitis C two years ago, genotype 1a, no cirrhosis on staging, and completed a standard 12-week course of first-line direct-acting antiviral therapy eight months ago. His follow-up viral load at 12 weeks post-treatment, drawn at a routine visit he almost missed because of his schedule, came back detectable — a genuine treatment failure rather than the sustained virologic response that would have counted as cure.
A three-drug salvage regimen combining a protease inhibitor with the two drug classes from his original therapy is the guideline-preferred retreatment option for exactly this situation: POLARIS-1 (Bourlière et al.) tested sofosbuvir-velpatasvir-voxilaprevir in DAA-experienced patients and reported cure in the high nineties, essentially irrespective of baseline resistance-associated substitutions — which is the specific reason the resistance question below is arguable rather than obligatory. Whether to also send resistance-associated substitution testing before starting that regimen, and whether his failure actually reflects viral resistance as opposed to a treatment course he didn't fully complete given how much of the past three months he's spent away from home, are the two questions sitting underneath what looks on the surface like a straightforward retreatment decision.
What actually needs answering before retreatment starts
I'd move straight to the salvage regimen without waiting on resistance testing. It has high demonstrated cure rates across DAA-experienced patients regardless of baseline resistance pattern, and I don't think the test result is likely to change what we prescribe today. Waiting on it just delays a retreatment he needs.
I'd still send the resistance testing, even agreeing it probably won't change today's regimen. If this second course also fails for any reason, having a documented baseline resistance profile from before this retreatment gives us real information for constructing a third, more individualized regimen under less time pressure than we'd have then. It's cheap to send now and potentially much more useful later than at that point.
'Won't change today's prescription' is true and also not the only question worth asking — not every useful test result needs to change today's decision to be worth having on record before it's needed.
I'd want us to answer something more basic before either of those points matters much: did he actually complete the first course as prescribed? He's been on the road four to five days a week for most of the treatment period, and incomplete adherence produces the identical positive follow-up viral load that true virologic resistance failure does, but it means something different for how we think about this retreatment and how hard we push adherence support the second time. That's a direct conversation nobody's had with him yet, as far as the chart shows.
Salvage retreatment started. Resistance-associated substitution testing was sent for the record, per the infectious disease physician's request, though it was not awaited before starting therapy.
A direct adherence conversation was had with Roberto at this visit, which he candidly acknowledged — he missed several doses during a particularly demanding stretch of his route. Adherence support, including a pillbox designed for his travel schedule, was built into the retreatment plan explicitly rather than assumed to be a solved problem this time.