I am an ID fellow and am seeking advice concerning NRTIs in the case of a patient who was naive to HAART treatment and placed on Combivir and nelfinavir (as you can probably guess). She never became undetectable and escaped viral suppression recently. The following genotype mutations were also present:
Dr. Brian Conway responds: For a patient placed on zidovudine, lamivudine and nelfinavir, the mutational pattern is not unexpected. In the RT gene, the M184V change confers high-grade lamivudine resistance. The D67N was selected by the zidovudine, and would also confer some degree of cross-resistance to abacavir. Susceptibility to other NRTIs (such as didanosine) would be expected to remain intact. The NNRTIs also remain available for use, with the mutation at codon 98 being of little significance, in the absence of other changes.
In the protease gene, D30N is the classic primary nelfinavir resistance mutation. This has likely been present for some time, as an additional three secondary mutations (at codons 10, 20 and 36) have emerged. The changes at codons 63 and 64 should not be considered significant. Given these additional changes, the clinical efficacy of agents such as indinavir and saquinavir would be compromised. If one were to select a PI, a more appropriate choice might be amprenavir or Kaletra, which would be active against isolates with such evolving mutational patterns.
Given the data you are presenting, it appears that questions of adherence to therapy may be an issue with your patient. Accordingly, I might select an easier once-daily regimen with didanosine (as Videx-EC), tenofovir and either efavirenz or nevirapine. The possible drug interaction between Videx-EC and tenofovir (increasing didanosine toxicity) would have to be monitored, and may lead to a need to reduce the daily dose of Videx-EC. The importance of adherence to therapy would have to be reinforced, to maximize the likelihood of virologic suppression.
