A phylotype-based analysis highlights the role of drug-naive HIV-positive individuals in the transmission of antiretroviral resistance in the UK.

TitleA phylotype-based analysis highlights the role of drug-naive HIV-positive individuals in the transmission of antiretroviral resistance in the UK.
Publication TypeJournal Article
Year of Publication2015
AuthorsMourad R, Chevennet F, Dunn D, Fearnhill E, Delpech V, Asboe D, Gascuel O and Hue S
Corporate AuthorsUK HIV Drug Resistance Database & the Collaborative HIV, Anti-HIV Drug Resistance Network
JournalAIDS
Volume29
Issue15
Pagination1917-25
Date Published2015 Sep 24
ISSN1473-5571
KeywordsCohort Studies, Computational Biology, Disease Transmission, Infectious, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV-1, Humans, Male, Molecular Epidemiology, Phylogeny, pol Gene Products, Human Immunodeficiency Virus, Sequence Analysis, DNA, United Kingdom
Abstract

OBJECTIVE: Antiretroviral-naive HIV-positive individuals contribute to the transmission of drug-resistant viruses, compromising first-line therapy. Using phylogenetic inference, we quantified the proportion of transmitted drug-resistance originating from a treatment-naive source.METHODS: Using a novel phylotype-based approach, 24 550 HIV-1 subtype B partial pol gene sequences from the UK HIV Drug Resistance database were analysed. Ongoing transmission of drug resistance amongst HIV-positive individuals was identified as phylotypes of at least three sequences with at least one shared drug resistance mutation, a maximum intra-clade genetic distance of 4.0% and a basal branch support at least 90%. The time of persistence of the transmission chains was estimated using a fast least-squares molecular clock inference approach.RESULTS: Around 70% of transmitted drug-resistance had a treatment-naive source. The most commonly transmitted mutations were L90M in the protease gene and K103N, T215D and T215S in reverse transcriptase. Reversion to wild type occurred at a low frequency and drug-independent reservoirs of resistance have persisted for up to 13 years.CONCLUSION: These results illustrate the impact of viral fitness on the establishment of resistance reservoirs and support the notion that earlier diagnoses and treatment of HIV infections are warranted for counteracting the spread of antiretroviral resistance. Phylotype-based phylogenetic inference is an attractive approach for the routine surveillance of transmitted drug resistance in HIV as well as in other pathogens for which genotypic resistance data are available.

DOI10.1097/QAD.0000000000000768
Alternate JournalAIDS
PubMed ID26355570
Grant ListMC_UU_12023/15 / / Medical Research Council / United Kingdom
MR/M004236/1 / / Medical Research Council / United Kingdom
092807 / / Wellcome Trust / United Kingdom
/ / Biotechnology and Biological Sciences Research Council / United Kingdom