Absence of genotypic drug resistance and presence of several naturally occurring polymorphisms of human immunodeficiency virus-1 CRF06_cpx in treatment-naive patients in Estonia

• Published in: Journal of medical virology Vol. 81; no. 6; pp. 953 - 958
• Main Authors: Avi, Radko, Huik, Kristi, Sadam, Maarja, Karki, Tonis, Krispin, Tonu, Ainsalu, Külliki, Paap, Piret, Schmidt, Jelena, Nikitina, Natalia, Lutsar, Irja
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2009; Wiley
• Subjects: Adult; Biological and medical sciences; drug resistance mutation; Drug Resistance, Viral; env Gene Products, Human Immunodeficiency Virus - genetics; Estonia; Female; Fundamental and applied biological sciences. Psychology; Genotype; HIV Infections - virology; HIV Protease - genetics; HIV Reverse Transcriptase - genetics; HIV-1 - classification; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; Mutation, Missense; natural polymorphism; Phylogeny; Polymorphism, Genetic; protease; revertase; RNA, Viral - genetics; Sequence Analysis, DNA; Sequence Homology; Viral diseases; Virology; Eastern Europe; Europe; Estonia; Human; Drug; RNA-directed DNA polymerase; Enzyme; Transferases; Retroviridae; revertase; Lentivirus; Virus; Resistance; protease; Nucleotidyltransferases; drug resistance mutation; Treatment; natural polymorphism; Mutation; Human immunodeficiency virus; Polymorphism
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.21482

All non-B HIV-1 subtypes and circulating recombinant forms (CRFs) are characterized by several polymorphisms in protease (PR) region. In addition, in recent years the increasing use of antiretroviral treatment (ART) has rapidly raised the spread of transmitted drug resistance. We aimed to determine the presence of naturally occurring polymorphisms and transmitted drug resistance mutations (DRMs) in ART naïve HIV-1-positive subjects in Estonia. A total of 115 drug-naive HIV-1-infected subjects (mean age 27 years; 70% male; 65% infected via intravenous drug use and 34% by heterosexual contact) were enrolled. Viral genomic RNA from plasma was directly sequenced in PR, revertase (RT), and envelope (env) regions. Phylogenetic analysis of RT and env regions revealed that 89% and 3% of sequenced viruses belonged to CRF06_cpx and subtype A1, respectively, and 6% were described as unique recombinants (signed A1-06) between CRF06_cpx and subtype A1 viruses. No primary DRMs were found in PR or RT regions indicating the absence of transmitted drug resistance. The most common polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%, 99%, and 100%, respectively. The clinical relevance of these polymorphisms in terms of success of ART has to be monitored in future clinical studies. J. Med. Virol. 81:953-958, 2009.