title: Longitudinal Trends in Western Australian HIV-1 Sequence Diversity and Viral Transmission Networks and Their Influence on Clinical Parameters: 2000-2014.
abstract: We examined baseline HIV-1 protease and reverse transcriptase sequences and HIV clinical parameters from 1,021 consecutive patients (814 male, 207 female) through the Royal Perth Hospital HIV service to investigate HIV-1 subtype diversity and local phylogenetic networks from 2000 to 2014. HIV-1 subtype B virus sequences were demonstrated in 619 (61%) of cases, with increasing non-B HIV-1 subtypes from 23.2% (2000-2003) to 48% (2008-2011) and 43% (2012-2014) (p < 0.001), including the CRF01_AE subtype [6.6% (2000-2003) to 21.5% (2008-2011)] and HIV-1 C subtype [9.5% (2000-2003) to 20.2% (2008-2011)]. More HIV-1 B subtypes were assigned to phylogenetic clusters compared to non-B subtypes (34% vs. 18%; p < 0.001), with larger clusters identified (cluster size >2: 135/211; 64% vs. 13/69; 19%; p = 0.001), including one cluster of 53 HIV-1 B subtype sequences that evolved from 2008 to 2014. Non-B subtype HIV-1 was associated with lower baseline CD4 T cell count (p = 0.005) but not plasma HIV-1 RNA levels (p = 0.31), suggesting relatively delayed diagnosis. Baseline viral load was strongly associated with calendar time [mean 18,620 copies/ml in 2000-2003; 75,858 copies/ml in 2012-2014 (p < 0.001)], and was also associated with larger phylogenetic clusters (size >2) in adjusted analyses (p = 0.03). This study identifies a number of temporal trends over the past 15 years, including an increasing prevalence of non-B subtype HIV-1 that highlights the growing influence of migration and travel on the Australian HIV-1 epidemic and the associated increased role of heterosexual HIV-1 transmission in this context. At the same time, these data indicate that local transmission within predominantly male networks remains a challenging issue for HIV-1 prevention.
authors.affiliation: 1 Department of Clinical Immunology, Royal Perth Hospital , Perth, Western Australia.|2 School of Veterinary and Life Sciences, Murdoch University , Perth, Western Australia.
authors.forename: Alison S L
authors.initials: AS
authors.lastname: Castley
authors.affiliation: 3 Institute of Immunology and Infectious Diseases, Murdoch University , Murdoch, Australia .|4 School of Anatomy, Physiology and Human Biology, University of Western Australia , Nedlands, Australia .|5 Division of Infectious Diseases, Department of Medicine, Vanderbilt University , Nashville, Tennessee.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaudieri
authors.affiliation: 3 Institute of Immunology and Infectious Diseases, Murdoch University , Murdoch, Australia .
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.affiliation: 1 Department of Clinical Immunology, Royal Perth Hospital , Perth, Western Australia.
authors.forename: Laila S
authors.initials: LS
authors.lastname: Gizzarelli
authors.affiliation: 1 Department of Clinical Immunology, Royal Perth Hospital , Perth, Western Australia.
authors.forename: George
authors.initials: G
authors.lastname: Guelfi
authors.affiliation: 1 Department of Clinical Immunology, Royal Perth Hospital , Perth, Western Australia.|3 Institute of Immunology and Infectious Diseases, Murdoch University , Murdoch, Australia .
authors.forename: Mina
authors.initials: M
authors.lastname: John
authors.affiliation: 1 Department of Clinical Immunology, Royal Perth Hospital , Perth, Western Australia.|3 Institute of Immunology and Infectious Diseases, Murdoch University , Murdoch, Australia .
authors.forename: David
authors.initials: D
authors.lastname: Nolan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018562:Disease Transmission, Infectious; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000473:pathology / Q000635:transmission* / 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; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D010802:Phylogeny; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D019562:Viral Load; D014904:Western Australia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1