There's no easy answer to this question. The 263K mutation causes intermediate bictegravir resistance, with about a 2-fold loss of susceptibility. Whether that's a contraindication to the use of Biktarvy is unclear. The fact that his labs look good early on is somewhat reassuring, but it doesn't really answer the question, because you'd expect an early response, even in a regimen with partial activity. If it were me, I'd want to be on something else. However, given his anxiety, I wouldn't want to alarm him. I'd say something like this: "Your resistance test shows a mutation in your virus that could lower the activity of one of the three drugs contained in Biktarvy. You're doing great, and it would probably work anyway, but the safest thing might be to switch you to a different combination where all three drugs are fully active." Of course, he might ask, "Can't we just wait and see how it goes?" It's a reasonable question, but then he runs the risk of developing new mutations to NRTIs and/or INSTIs if he fails.
Ultimately, it's up to him, but he needs to be informed. Make sure you get a viral load if you switch.
Good luck!
Original Message:
Sent: 6/24/2025 3:24:00 PM
From: Victoria Behrman
Subject: pt with 2nd gen INSTI mutation
Hi everyone, I recently saw a new patient, a guy who was diagnosed with HIV in February 2025. He was evaluated in a clinic near where I work & had baseline labs sent including a genotype; then had same-day/ rapid start of biktarvy. A few weeks later, he was arrested & booked at the jail where I work, & had another set of monitoring labs sent. The new monitoring labs looked good: CD4 had risen from 340/15% to 480/24%, and his VL dropped from around 1000 copies to undetectable. So that's all fine! The only glitch is that the genotype results showed an INSTI gene mutation, R263K, which I gather is associated with 2nd generation INSTI resistance. I have not changed his regimen, because (a) the biktarvy is clearly working well, and (b) he is anxious & somewhat overwhelmed about his new HIV diagnosis & needed a lot of reassurance, and it just didn't seem like the right time at that first visit to introduce doubts about his meds or to start discussing a possible switch. But I would welcome thoughts from other experienced HIV clinicians about this case. Have other people seen this mutation? Any suggestions on management, other than close monitoring? Thanks!
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Victoria Behrman MD
Berkeley CA
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