Twenty Years of Vivid Dreams
Twenty years of tolerated side effects is its own kind of evidence that something should change — the complication is that the one record that would make the switch straightforward predates his clinic's electronic chart by a decade.
W.H., a 55-year-old man, was diagnosed with HIV in 2003 and started on efavirenz, zidovudine, and lamivudine — a standard regimen at the time — later simplified over the years to efavirenz with tenofovir and emtricitabine as newer formulations became available. He has held a steady job as a building superintendent for over fifteen years and describes himself, only half joking, as having read more novels than anyone he knows, a habit that started specifically because efavirenz's vivid dreams and disrupted sleep left him wide awake most nights and he decided he might as well use the time. He has never missed enough doses to fail therapy in close to two decades, but the CNS side effects — the dreams, a persistent difficulty concentrating some mornings, and what he describes as a low-grade flatness of mood he's never been sure is depression or just efavirenz — have never fully resolved either, and he's asking, not for the first time, whether there's finally something else he could take. He's raised this same question at several prior visits over the years, and by his own account has mostly been told the side effects were something he'd simply learn to manage.
His chart does hold one complication. A viral load check in 2006 showed a rebound to 8,200 copies/mL after a period of documented poor adherence during a difficult stretch following a divorce, and resistance testing was reportedly sent at that time — but his clinic switched electronic health record systems in 2011, and the actual genotype result from that episode was never migrated and cannot now be located. He resuppressed afterward and has remained undetectable ever since. SWORD-1 and SWORD-2 established dolutegravir/rilpivirine as a safe, effective switch option in stable patients, and TANGO did the same for dolutegravir/lamivudine — but both trials specifically excluded anyone with a history of virologic failure or resistance to the regimen's own components, a criterion his 2006 episode makes genuinely unclear rather than confidently met. Nineteen years of otherwise unbroken suppression sit on one side of that gap, and a single unrecoverable lab result sits on the other.
HIV clinic, annual visit
Twenty years of disrupted sleep and morning concentration problems is a real, ongoing cost, not a minor complaint he's simply learned to live with. SWORD and TANGO both support switching stable patients to a simplified two-drug regimen, and he is about as stable as a patient gets. I'd move him to dolutegravir/rilpivirine.
I don't doubt his symptoms are real and I'm not arguing he should stay on efavirenz indefinitely.
But both of those switch trials specifically excluded patients with a documented virologic-failure history and unclear resistance status to the regimen's own components — and his 2006 rebound with a genotype we can no longer locate is precisely that gap, not a technicality. A two-drug regimen has a thinner margin than a three-drug one if there's undetected resistance sitting in his reservoir. And his CD4 of 710 today doesn't tell us anything useful here — immune recovery and archived resistance are two separate questions, and nineteen years of a healthy count says nothing about what's sitting in his reservoir from that one rough stretch. I'd want more certainty before moving him onto a regimen whose safety data doesn't actually cover his situation.
The 2006 genotype is gone, but that's not the only way to answer the question. A proviral DNA test today would show whatever resistance-associated mutations are still archived in his current reservoir — that's actually more directly relevant to a switch decision now than a nineteen-year-old lab report would have been anyway, since it reflects what's actually present today rather than a single moment from two decades ago. I'd order that before finalizing either direction.
Agreed: proviral DNA genotype ordered today, with efavirenz continued unchanged in the meantime rather than switching blind. If the archived reservoir shows no resistance to dolutegravir or rilpivirine, the switch proceeds at his next visit; if it shows anything concerning, a three-drug alternative with a better CNS profile — such as dolutegravir with tenofovir alafenamide and emtricitabine — becomes the fallback discussed with him directly.