In the case of a patient who has D67N,T69D,T215Y,G333E,G190A and L10I mutations, who has been taking lopinavir/r, d4T, tenofovir and ddI, and who initially responded but is now rebounding with the current regimen, should one consider dual PI (saquinavir/ritonavir) + ddI + Epivir? Any suggestions?
With respect to the NRTIs, the combination of mutations at codons 67, 69 and 215 will likely compromise the efficacy of all the drugs in this class, except for tenofovir. Although it is correct to say that the efficacy of tenofovir is compromised by the presence of nucleoside-associated mutations (NAMs), this only seems to occur if three or more such mutations are present, including mutations at codons 41 or 210.
With respect to NNRTIs, the mutation at codon 190 compromises the efficacy of efavirenz or nevirapine (likely due to exposure to one or both of these drugs in prior regimens). Interestingly, this mutation may confer increased susceptibility to delavirdine, making it a potentially attractive choice in this setting.
With respect to PIs, the presence of an isolated secondary resistance mutation at codon 10 is of little clinical consequence.
Thus, in the current regimen, the ddI and d4T are likely ineffective, and the virologic breakthrough may well relate to the fact that we are relying on tenofovir and Kaletra to do all the work. It makes sense to keep these two drugs in the regimen. I might add delavirdine. In addition to its own efficacy, it will exert a beneficial effect on the levels of Kaletra in the circulation, and perhaps enhance its efficacy.
Alternatively, a true double protease inhibitor regimen (such as lopinavir/r with amprenavir) may be required (along with continued tenofovir), although pharmacokinetic interactions between lopinavir, ritonavir and amprenavir may be a bit unpredictable, and should be measured at steady state if you have access to such a test.
