Quantifying the fitness cost of HIV-1 drug resistance mutations through phylodynamics. PLoS Pathogens
Kühnert et al. aimed to employ a phylodynamic approach to quantify the fitness costs of major resistance mutations in the Swiss HIV cohort. The authors modelled the transmission tree using stochastic birth-death-sampling processes, including hosts infected by a sensitive or resistant strain. In terms of the transmission tree a “birth” event corresponded to the infection of a new host, a “death” event corresponded to the host’s removal from the infectious pool (e.g. successful treatment).
For this study, the following resistance mutations were included: 41L, 67N, 70R, 184V, 210W, 215D, 215S and 219Q (nRTI-related) and 103N, 108I, 138A, 181C, 190A (NNRTI-related) in the reverse transcriptase and the 90M mutation in the protease gene. Among these resistance mutations, only the 90M mutation in the protease gene was found to have significantly higher fitness than the drug sensitive strains. The following mutations associated with resistance to reverse transcriptase inhibitors were found to be less fit than the sensitive strains: 67N, 70R, 184V, 219Q. For the remaining resistance mutations included in this study, all the mutations did not have a significant effect on viral transmissibility within the Swiss HIV cohort.
In conclusion, the authors present a phylogenetic approach that allows direct quantification of population-level fitness costs of HIV resistance mutations from viral sequence data alone. Hence, this approach may become particularly useful in assessing the risk of transmitted drug resistance in resource limited settings where resistance testing is possible but epidemiological, demographic and clinical data are missing. Furthermore, this new approach is not only applicable to HIV but to any measurably evolving pathogen.