HIV-1 pol gene variation is sufficient for reconstruction of transmissions in the era of antiretroviral therapy

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Abstract
Objectives: We wished to assess the potential of using HIV-1 pol gene for the identification of transmissions events by phylogenetic means in the era of antiretroviral drug selective pressure. Design: The relatedness of the viruses within a large database of pol sequences generated from HIV-1 infected individuals from the UK was reconstructed by phylogenetic analyses. Methods: A total of 140 pol sequences were selected out of the 2500 database entries, on the basis of a pairwise genetic distance higher than 95%. Neighbour Joining and Maximum Likelihood trees were implemented. Trees were reconstructed after exclusion of codon positions associated with drug resistance from the original pol alignment. Trees based on the corresponding env and gag genes were implemented to confirm the linkages. Results: Up to 23 transmission clusters were identified, supported by high bootstrap values (> 99), congruent epidemiological data and/or similar drug resistance motifs. The topology of the tree was consistent after exclusion of the drug resistance associated codons. Identical topologies were obtained in trees implemented from gag and env genes alignments. Conclusions: Despite its genetic conservation, the HIV-1 pol gene holds sufficient variability to permit the phylogenetic reconstruction of transmissions. Identical clusters were obtained whichever of the three principal genes is considered and no bias was induced by the presence of drug resistance mutations. These findings demonstrate the important epidemiological information inherent within routinely collected laboratory data, which can assist in estimating rates of recent HIV-1 transmission within a population.