Covariation of mutation pairs expressed in HIV-1 protease and reverse transcriptase genes subjected to varying treatments

A previous study, focused on the correlation of mutation pairs of synonymous (S) and asynonymous (A) mutations, distinguished only between the treated and untreated data of protease and reverse transcriptase (RT) of HIV-1 subtype B. It is well known that single mutation patterns in HIV-1 are treatment-specific. It logically follows that covariation between mutations will also be treatment specific. Thus, our motivation is to give a more in depth study of the covariation between mutation pairs, analyzing not only treated and untreated, but what specific treatments were used, and how they affected the covariation between the mutations differently. We intended to further deepen this study by analyzing the covariation of mutations in protease and RT in different subtypes of HIV-1. We found that virus samples subjected to antiretroviral Proteaseand RTinhibitors do show different patterns of mutation covariation in B-subtype protease and RT of HIV-1, while maintaining the same overall trend. covariation will tend to be higher and more distinct from and covariation after treatment. The same trend continues in protease and RT regardless of subtype. We also found the highly covaried codon positions, position pairs, and positioncovariation clusters in protease, affected by different treatments. Most of them are well known major drug-resistance sites for these treatments.