Thanks for your post, Dr. Corigliano.
First off, a compilation of your patient's drug resistance mutations into the
Stanford HIV drug resistance database
suggests:
susceptibility to: TDF, LPV/RTV, fAPV, TPV
high level resistance to: 3TC, FTC,
low level resistance to: AZT, d4T, ABC, ATV, IDV, SQV, DRV
possible low level resistance to: ddI, NFV
The clinical pattern of virologic suppression and declining CD4 lymphocyte counts have been reported, particularly among patients receiving TDF with full dose ddI (400 mg daily). You're also correct insomuch that as part of triple nucleoside treatments, the TDF and ABC combination has been associated with higher rates of treatment failure. There is less compelling data about this loss of virologic control as part of other two-class, three or four drug regimens.
Given that your patient is already suppressed, the risk of emergent mutations is probably lower and the switch that you've proposed is not unreasonable.
I'd offer a couple of other possibilities:
First, since FTC and 3TC resistance (M184V) potentiates the susceptibility to tenofovir, the combinations of TDF/FTC or TDF+3TC could be entertained.
Second, I'm concerned about the interaction of TDF with atazanavir in the setting of potential impairment of the potency of either the NRTI or PI backbones, since TDF lowers atazanavir levels. If you're concerned about the potency of the NRTI side of the regimen, perhaps a switch to boosted fosamprenavir or lopinavir could be entertained-- in order to avoid this negative drug-drug interaction (indeed, the later would actually increase TDF exposure as well).
I hope this helps.
Feel free to write back with any questions. BY
