We present a patient with chronic HIV-1 infection and primary multi-drug resistance, the magnitude of which was underestimated by the baseline genotypic resistance testing (GRT) due to reversion of some of the mutations of the transmitted strain. This resulted in complete failure of his first antiretroviral regimen with rapid appearance of presumably archived mutations to more than one antiretroviral classes. Interestingly, his viral load remained high even in the presence of the M184V mutation. Baseline GRT in chronic HIV infection may not give adequate information in the presence of acquired multi-drug-resistant HIV strains, which have one or more of their mutations reverted. The presence of 215 codon polymorphisms should alert physicians to the possible coexistence of archived nucleoside and non-nucleoside reverse transcriptase inhibitor mutations. In such a case, initiation of a regimen with a low genetic barrier to resistance may not be the best choice and, if done, should be done cautiously and with more frequent monitoring of treatment response than usual.