Demonstration of Sustained Drug-Resistant Human Immunodeficiency Virus Type 1 Lineages Circulating among Treatment-Naïve Individuals
- 15 March 2009
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 83 (6) , 2645-2654
- https://doi.org/10.1128/jvi.01556-08
Abstract
Transmission of human immunodeficiency virus (HIV) drug resistance is well-recognized and compromises response to first-line therapy. However, the population dynamics of transmitted resistance remains unclear, although previous models have assumed that such transmission reflects direct infection from treated individuals. We investigated whether population-based phylogenetic analyses would uncover lineages of resistant viruses circulating in untreated individuals. Through the phylogenetic analysis of 14,061 HIV type 1 (HIV-1)polgene sequences generated in the United Kingdom from both treatment-naïve and -experienced individuals, we identified five treatment-independent viral clusters containing mutations conferring cross-resistance to antiretroviral drugs prescribed today in the United Kingdom. These viral lineages represent sustainable reservoirs of resistance among new HIV infections, independent of treatment. Dated phylogenies reconstructed through Bayesian Markov chain Monte Carlo inference indicated that these reservoirs originated between 1997 and 2003 and have persisted in the HIV-infected population for up to 8 years. Since our cohort does not represent all infected individuals within the United Kingdom, our results are likely to underestimate the number and size of the resistant reservoirs circulating among drug-naïve patients. The existence of sustained reservoirs of resistance in the absence of treatment has the capacity to threaten the long-term efficacy of antiretroviral therapy and suggests there is a limit to the decline of transmitted drug resistance. Given the current decrease in resistance transmitted from treated individuals, a greater proportion of resistance is likely to come from drug-naïve lineages. These findings provide new insights for the planning and management of treatment programs in resource-rich and developing countries.Keywords
This publication has 50 references indexed in Scilit:
- Persistence of Transmitted Drug Resistance among Subjects with Primary Human Immunodeficiency Virus InfectionJournal of Virology, 2008
- Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infectionProceedings of the National Academy of Sciences, 2008
- Episodic Sexual Transmission of HIV Revealed by Molecular PhylodynamicsPLoS Medicine, 2008
- Phylogenetic Surveillance of Viral Genetic Diversity and the Evolving Molecular Epidemiology of Human Immunodeficiency Virus Type 1Journal of Virology, 2007
- BEAST: Bayesian evolutionary analysis by sampling treesBMC Ecology and Evolution, 2007
- The Fitness Cost of Mutations Associated with Human Immunodeficiency Virus Type 1 Drug Resistance Is Modulated by Mutational InteractionsJournal of Virology, 2007
- Identification of accessory mutations associated with high-level resistance in HIV-1 reverse transcriptaseAIDS, 2007
- Time trends in primary resistance to HIV drugs in the United Kingdom: multicentre observational studyBMJ, 2005
- Emerging Drug Targets for Antiretroviral TherapyDrugs, 2005
- Toward Defining the Course of Evolution: Minimum Change for a Specific Tree TopologySystematic Zoology, 1971