Use of new resistance markers to predict virologic response to antiretrovirals

Abstract

Results Among the reasons that more ultrasensitive assays may sometimes be needed for more accurate assessments of drug resistance is the differential effect of certain mutations on viral replicative capacity. As an example, the K65R mutation is known to adversely affect HIV replication, and this may be one of the reasons that it is found relatively infrequently among individuals who fail antiretroviral therapy. In contrast, the use of AS-PCR for K65R in subtype C viruses has shown that this method was able to detect the presence of this mutation in an additional 4 of 30 samples who had tested negative by bulk sequencing methods. Now, it also appears as though the transmission of the K65R mutation, while rare, can also be detected in higher numbers by AS-PCR than bulk sequencing, and that this is also more common among subtype C than subtype B viruses. The likely reason is that subtype C viruses are more prone to develop K65R as a consequence of treatment failure and are therefore more likely than subtype B viruses to contain this mutation at the time that transmission takes place. In the case of the M184V mutation, it has also been observed that AS-PCR methods can detect this substitution more efficiently than bulk sequencing among newly-infected individuals.