Evolutionary pathways of transmitted drug-resistant HIV-1

• Published in: Journal of antimicrobial chemotherapy Vol. 66; no. 7; pp. 1467 - 1480
• Main Authors: Pingen, Marieke, Nijhuis, Monique, de Bruijn, Johan A., Boucher, Charles A. B., Wensing, Annemarie M. J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-07-2011; Oxford Publishing Limited (England)
• Subjects: Amino acids; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Biological Evolution; Disease transmission; Drug resistance; Drug Resistance, Viral; Europe; Evolution; HIV; HIV Infections - transmission; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - isolation & purification; HIV-1 - pathogenicity; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infection; Infectious diseases; Medical sciences; Mutation; Pharmacology. Drug treatments; Public health; Replication; Reversion; Selection, Genetic; United States; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virulence; United States; Europe; United States > US; persistence; transmission; evolution; resistance; Immunopathology; Treatment resistance; HIV-1 virus; Biological evolution; Transmission; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Persistence; Viral disease; Human immunodeficiency virus
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkr157

Several large studies in Europe and the USA revealed that approximately 10% of all newly diagnosed patients harbour HIV-1 variants with at least one major resistance-associated mutation. In this review we discuss the underlying mechanisms that drive the evolution of drug-resistant viruses after transmission to the new host. In a comprehensive literature search 12 papers describing the evolution of 58 cases of transmitted resistant HIV-1 variants were found. Based on observations in the literature we propose three pathways describing the evolution of resistant HIV-1 after transmission to a new host. Firstly, reversion of the resistance mutation towards wild-type may rapidly occur when drug resistance mutations severely impact replicative capacity. Alternatively, a second pathway involves replacement of transmitted drug resistance mutations by atypical amino acids that also improve viral replication capacity. In the third evolutionary pathway the resistance mutations persist either because they do not significantly affect viral replication capacity or evolution is constrained by fixation through compensatory mutations. In the near future ultra-sensitive resistance tests may provide more insight into the presence of archived and minority variants and their clinical relevance. Meanwhile, clinical guidelines advise population sequence analysis of the baseline plasma sample to identify transmission of resistance. Given the limited sensitivity of this technique for minority populations and the delay between the moment of infection and time of analysis, knowledge of the described evolutionary mechanisms of transmitted drug resistance patterns is essential for clinical management and public health strategies.