Polymorphisms and Mutational Covariation Associated with Death in a Prospective Cohort of HIV/AIDS Patients Receiving Long-Term ART in China

Autor: Zhe Wang, Pengtao Liu, Hui Xing, Lingjie Liao, Yuhua Ruan, Bin Su, Jianjun Wu, Sui-an Tian, Yinghui You, Yiming Shao, Yi Feng
Rok vydání: 2017
Předmět:
Male
RNA viruses
0301 basic medicine
Gerontology
Oncology
lcsh:Medicine
HIV Infections
Drug resistance
Pathology and Laboratory Medicine
Cohort Studies
Database and Informatics Methods
Immunodeficiency Viruses
Amino acid mutation
Medicine and Health Sciences
Public and Occupational Health
Drug Interactions
Prospective Studies
lcsh:Science
Prospective cohort study
media_common
Multidisciplinary
Vaccination and Immunization
HIV Reverse Transcriptase
Medical Microbiology
Viral Pathogens
Viruses
Female
Pathogens
Sequence Analysis
HIV drug resistance
Research Article
Adult
Drug
China
medicine.medical_specialty
Anti-HIV Agents
Bioinformatics
media_common.quotation_subject
Immunology
Antiretroviral Therapy
Sequence Databases
Research and Analysis Methods
Microbiology
03 medical and health sciences
Antiviral Therapy
Acquired immunodeficiency syndrome (AIDS)
Microbial Control
Internal medicine
Drug Resistance
Viral
Retroviruses
Genetics
medicine
Humans
Microbial Pathogens
Pharmacology
Acquired Immunodeficiency Syndrome
Polymorphism
Genetic
business.industry
lcsh:R
Lentivirus
Organisms
Biology and Life Sciences
HIV
medicine.disease
Antiretroviral therapy
Biological Databases
030104 developmental biology
Mutation
Mutation Databases
HIV-1
lcsh:Q
Antimicrobial Resistance
Preventive Medicine
business
Clinical progression
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 1, p e0170139 (2017)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0170139
Popis: Background HIV drug resistance is associated with faster clinical progression of AIDS. However, the effect of significant polymorphisms and mutational covariation on mortality among HIV/AIDS patients receiving long-term antiretroviral therapy (ART), have rarely been studied. Methods In this prospective cohort study from December 2003 to December 2014, we present a new computational modelling approach based on bioinformatics-based models and several statistical methods to elucidate the molecular mechanisms involved in the acquisition of polymorphisms and mutations on death in HIV/AIDS patients receiving long-term ART in China. Results This study involved 654 ART-treated patients, who had been followed for 5473.4 person-years, a median of 9.8 years, and 178 died (25.2%, 3.3/100 person-years). The first regimens included AZT/d4T + NVP+ ddI (78.9%) or AZT/d4T + NVP+ 3TC (20.0%). We calculated an individual Ka/Ks value for each specific amino acid mutation. Result showed that 20 polymorphisms (E6D, Q18H, E35D, S37N, T39A, K43E, S68N, L74I, I93L, K103N, V106A, E169D, Y181C, G190A, Q197K, T200V, T200E, T215I, E224D and P225H) were strongly associated with AIDS related deaths. Among them, 7 polymorphisms (L74I, K103N, V106A, Y181C, G190A, T215I and P225H) were known to be drug resistance mutations, 7 polymorphisms (E6D, E35D, S37N, I93L, E169D, T200V and T200E were considered to be potential drug resistance mutations, and 6 polymorphisms (T39A, K43E, S68N, Q197K, T200V and E224D) were newly found to have an association with drug resistance mutations, which formed a complex network of relationships. Conclusions Some polymorphisms and mutational covariation may be the important influencing factors in the failure of treatment. Understanding these mechanisms is essential for the development of new therapies, designing optimal drug combinations, and determining effective clinical management of individual patients.
Databáze: OpenAIRE
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