title: 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.
abstract: 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.
authors.affiliation: Faculty of Medicine, Department of Microbiology, University of Tartu, Tartu, Estonia. radko.avi@gmail.com
authors.forename: Radko
authors.initials: R
authors.lastname: Avi
authors.forename: Kristi
authors.initials: K
authors.lastname: Huik
authors.forename: Maarja
authors.initials: M
authors.lastname: Sadam
authors.forename: Tonis
authors.initials: T
authors.lastname: Karki
authors.forename: Tonu
authors.initials: T
authors.lastname: Krispin
authors.forename: Külliki
authors.initials: K
authors.lastname: Ainsalu
authors.forename: Piret
authors.initials: P
authors.lastname: Paap
authors.forename: Jelena
authors.initials: J
authors.lastname: Schmidt
authors.forename: Natalia
authors.initials: N
authors.lastname: Nikitina
authors.forename: Irja
authors.initials: I
authors.lastname: Lutsar
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral; D004957:Estonia; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase; D016333:HIV Protease