ArticleProceedings of the National Academy of Sciences of the United States of America1998
Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 160 citations in OpenAlex.
- Predictive genotypic algorithm for virologic response to lopinavir-ritonavir in protease inhibitor-experienced patients.Antimicrobial agents and chemotherapy · 2007Trial
- Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients.Antimicrobial agents and chemotherapy · 2005Trial
- Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients.Antimicrobial agents and chemotherapy · 2003Trial
- Next-Generation Sequencing Dataset Downloader and In Silico Sequence Mining: Graphical-User-Interface-Based Tools for Accessible, Multiprobe Target Mining in Next-Generation Sequencing Data.Computational and structural biotechnology journal · 2026Article
- Structural and Functional Studies on HIV Protease: Mechanism of Action, Subtypes, Inhibitors, and Drug Resistance.Methods in molecular biology (Clifton, N.J.) · 2025Review
- A classification algorithm based on dynamic ensemble selection to predict mutational patterns of the envelope protein in HIV-infected patients.Algorithms for molecular biology : AMB · 2023Article
- The Puzzle of HIV Neutral and Selective Evolution.Molecular biology and evolution · 2018Article
- Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.Retrovirology · 2018Article
- Article
- Driving HIV-1 into a Vulnerable Corner by Taking Advantage of Viral Adaptation and Evolution.Frontiers in microbiology · 2017Review
- Phylogenetically resolving epidemiologic linkage.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- Genetic Consequences of Antiviral Therapy on HIV-1.Computational and mathematical methods in medicine · 2015Review
- Timing and order of transmission events is not directly reflected in a pathogen phylogeny.Molecular biology and evolution · 2014Article
- Loss and recovery of genetic diversity in adapting populations of HIV.PLoS genetics · 2014Article
- Quantifying selection against synonymous mutations in HIV-1 env evolution.Journal of virology · 2013Article
- Impact of antiretroviral pressure on selection of primary human immunodeficiency virus type 1 envelope sequences in vitro.The Journal of general virology · 2013Article
- Stochastic effects are important in intrahost HIV evolution even when viral loads are high.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- The dynamics of HIV-1 adaptation in early infection.Genetics · 2012Article
- Stochastic simulations suggest that HIV-1 survives close to its error threshold.PLoS computational biology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has long been assumed that HIV-1 evolution is best described by deterministic evolutionary models because of the large population size. Recently, however, it was suggested that the effective population size (Ne) may be rather small, thereby allowing chance to influence evolution, a situation best described by a stochastic evolutionary model. To gain experimental evidence supporting one of the evolutionary models, we investigated whether the development of resistance to the protease inhibitor ritonavir affected the evolution of the env gene. Sequential serum samples from five patients treated with ritonavir were used for analysis of the protease gene and the V3 domain of the env gene. Multiple reverse transcription-PCR products were cloned, sequenced, and used to construct phylogenetic trees and to calculate the genetic variation and Ne. Genotypic resistance to ritonavir developed in all five patients, but each patient displayed a unique combination of mutations, indicating a stochastic element in the development of ritonavir resistance. Furthermore, development of resistance induced clear bottleneck effects in the env gene. The mean intrasample genetic variation, which ranged from 1.2% to 5.7% before treatment, decreased significantly (P < 0.025) during treatment. In agreement with these findings, Ne was estimated to be very small (500-15,000) compared with the total HIV-1 RNA copy number. This study combines three independent observations, strong population bottlenecking, small Ne, and selection of different combinations of protease-resistance mutations, all of which indicate that HIV-1 evolution is best described by a stochastic evolutionary model.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.