Zhukova, A;
Dunn, D;
Gascuel, O;
(2023)
Modeling Drug Resistance Emergence and Transmission in HIV-1 in the UK.
Viruses
, 15
(6)
, Article 1244. 10.3390/v15061244.
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Abstract
A deeper understanding of HIV-1 transmission and drug resistance mechanisms can lead to improvements in current treatment policies. However, the rates at which HIV-1 drug resistance mutations (DRMs) are acquired and which transmitted DRMs persist are multi-factorial and vary considerably between different mutations. We develop a method for the estimation of drug resistance acquisition and transmission patterns. The method uses maximum likelihood ancestral character reconstruction informed by treatment roll-out dates and allows for the analysis of very large datasets. We apply our method to transmission trees reconstructed on the data obtained from the UK HIV Drug Resistance Database to make predictions for known DRMs. Our results show important differences between DRMs, in particular between polymorphic and non-polymorphic DRMs and between the B and C subtypes. Our estimates of reversion times, based on a very large number of sequences, are compatible but more accurate than those already available in the literature, with narrower confidence intervals. We consistently find that large resistance clusters are associated with polymorphic DRMs and DRMs with long loss times, which require special surveillance. As in other high-income countries (e.g., Switzerland), the prevalence of sequences with DRMs is decreasing, but among these, the fraction of transmitted resistance is clearly increasing compared to the fraction of acquired resistance mutations. All this indicates that efforts to monitor these mutations and the emergence of resistance clusters in the population must be maintained in the long term.
| Type: | Article |
|---|---|
| Title: | Modeling Drug Resistance Emergence and Transmission in HIV-1 in the UK |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/v15061244 |
| Publisher version: | https://doi.org/10.3390/v15061244 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | HIV-1, ancestral character reconstruction, drug resistance mutations, Humans, HIV-1, HIV Infections, Drug Resistance, Viral, Genotype, Mutation, HIV Seropositivity, United Kingdom, Anti-HIV Agents |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10173974 |
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