Phylogenetic investigation of transmission pathways of drug-resistant HIV-1 utilizing pol sequences derived from resistance genotyping.

摘要

OBJECTIVES: To investigate the nature of transmission links existing between patients recently infected with HIV strains containing transmitted drug resistance (TDR) mutations. METHODS: Virus from 63 individuals recently infected with HIV-1 containing TDR mutations was analyzed phylogenetically to determine virological links. Phylogenetic trees were reconstructed using maximum likelihood and distance-based methods. Monophyletic clusters detected on the basis of pol sequences were confirmed using env and gag sequences. Potential bias caused by the presence of drug resistance mutations was assessed by reanalyzing the pol sequence set after the omission of 16 drug resistance codons identified in the TDR population. RESULTS: Phylogenetic analysis revealed 9 apparent transmission clusters involving 24 of the 63 (38%) TDR patients. Each cluster was supported by high bootstrap values and low intracluster genetic distances. The 9 transmission clusters were confirmed in separate analyses using env and gag sequences and in pol sequences after the removal of codons associated with drug resistance. CONCLUSIONS: Pol sequences generated during baseline resistance genotyping for newly HIV-infected patients provide the opportunity for real-time phylogenetics to identify sources of multiple HIV transmission events. This study demonstrated the existence of several distinct clusters of patients whose TDR strains were linked. Several discrete clusters involving transmission of K103N- and/or M41L-resistant virus to multiple recipients were detected, suggesting that multiple transmission pathways can exist for viruses with the same resistance mutations.