Co-Evolution of Compensatory Mutation K43E with Mutation M41L in Long-Term HIV Antiretroviral Treatment

Background: Compensatory mutations have been observed to emerge with drug resistance (DR) mutations, but their effects on virological response to treatment have not been fully examined. In this study, we characterized the emergence and depletion dynamics of a compensatory mutation K43E that correlated with primary nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations in Chinese HIV patients on antiretroviral treatment. Method: Single Genome Amplification (SGA) was used to obtain the HIV-1 pol gene quasispecies in three patients over 6 years of Antiretroviral Therapy (ART) treatment. SGA sequences were analyzed by Markov Chain Monte Carlo (MCMC) phylogenetic trees with molecular clock to identify and track compensatory mutation K43E correlated with primary DR mutation M41L. We evaluated the relationship between potential compensatory mutation and DR mutations through Ka/Ks ratio, Jaccard similarity coefficient, and compared these with concurrent viral load data. Conclusion: We determined that a known compensatory mutation, K43E, frequently co-occurs with the drug resistance mutation M41L and may offer a significant advantage in the long-term survival of such drug resistant strains.