Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections

BackgroundThe number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission.MethodsBaseline HIV-1 pol sequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients' demographics, laboratory and clinical data, were retrieved anonymously. Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics.ResultsMultivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection with Chlamydia (p = 0.01) and infection with Hepatitis C virus (p = 0.017). More and larger transmission-clusters were identified among the subtype B infections (p < 0.001). Overall, in multivariate analysis, clustering was significantly associated with Caucasian origin, infection through homosexual contact and younger age (all p < 0.001). Bivariate analysis additionally showed a correlation between clustering and syphilis (p < 0.001), higher CD4 counts (p = 0.002), Chlamydia infection (p = 0.013) and primary HIV (p = 0.017).ConclusionsCombination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions. This finding elucidates observed epidemiological trends through molecular analysis, and justifies sustained focus in prevention on this high risk group.

[1]  C. Archibald,et al.  Estimates of HIV prevalence and incidence in Canada, 2005. , 2006, Canada communicable disease report = Releve des maladies transmissibles au Canada.

[2]  D. Swofford.  PAUP*: Phylogenetic analysis using parsimony (*and other methods), Version 4.0b10 , 2002 .

[3]  David Dunn,et al.  Demonstration of Sustained Drug-Resistant Human Immunodeficiency Virus Type 1 Lineages Circulating among Treatment-Naïve Individuals , 2009, Journal of Virology.

[4]  D. Pillay,et al.  Phylogenetic reconstruction of transmission events from individuals with acute HIV infection: toward more-rigorous epidemiological definitions. , 2009, The Journal of infectious diseases.

[5]  Martin Fisher,et al.  Transmission of HIV-1 during primary infection: relationship to sexual risk and sexually transmitted infections , 2005, AIDS.

[6]  C. Birch,et al.  Phylogenetic Investigation of Transmission Pathways of Drug-Resistant HIV-1 Utilizing Pol Sequences Derived From Resistance Genotyping , 2008, Journal of acquired immune deficiency syndromes.

[7]  Anne-Mieke Vandamme,et al.  Edinburgh Research Explorer Phylogenetic surveillance of viral genetic diversity and the evolving molecular epidemiology of human immunodeficiency virus type 1 , 2007 .

[8]  R. Rothenberg,et al.  Social network dynamics and HIV transmission , 1998, AIDS.

[9]  Stéphane Hué,et al.  HIV-1 pol gene variation is sufficient for reconstruction of transmissions in the era of antiretroviral therapy , 2004, AIDS.

[10]  R. Rothenberg,et al.  Risk network structure in the early epidemic phase of HIV transmission in Colorado Springs , 2002, Sexually transmitted infections.

[11]  Michael P. Cummings,et al.  PAUP* [Phylogenetic Analysis Using Parsimony (and Other Methods)] , 2004 .

[12]  O. Hamouda,et al.  HIV incidence increasing in MSM in Germany: factors influencing infection dynamics. , 2006, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[13]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[14]  Tommy F. Liu,et al.  Minority Human Immunodeficiency Virus Type 1 Variants in Antiretroviral-Naive Persons with Reverse Transcriptase Codon 215 Revertant Mutations , 2008, Journal of Virology.

[15]  Bernard Hirschel,et al.  The impact of transmission clusters on primary drug resistance in newly diagnosed HIV-1 infection , 2009, AIDS.

[16]  Spread programme,et al.  Transmission of drug-resistant HIV-1 in Europe remains limited to single classes , 2008, AIDS.

[17]  R. Janssen,et al.  Syphilis Epidemics and Human Immunodeficiency Virus (HIV) Incidence Among Men Who Have Sex With Men in the United States: Implications for HIV Prevention , 2005, Sexually transmitted diseases.

[18]  W. Doolittle,et al.  Microsporidia are related to Fungi: evidence from the largest subunit of RNA polymerase II and other proteins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[19]  John P. Huelsenbeck,et al.  MRBAYES: Bayesian inference of phylogenetic trees , 2001, Bioinform..

[20]  JD Lundgren,et al.  Updated European Recommendations for the Clinical Use of HIV Drug Resistance Testing , 2004, Antiviral therapy.

[21]  T. A. Hall,et al.  BIOEDIT: A USER-FRIENDLY BIOLOGICAL SEQUENCE ALIGNMENT EDITOR AND ANALYSIS PROGRAM FOR WINDOWS 95/98/ NT , 1999 .

[22]  K. Mandaliya,et al.  A sensitive in-house RT-PCR genotyping system for combined detection of plasma HIV-1 and assessment of drug resistance. , 2006, Journal of virological methods.

[23]  Anne-Mieke Vandamme,et al.  Drug Resistance Mutations for Surveillance of Transmitted HIV-1 Drug-Resistance: 2009 Update , 2009, PloS one.

[24]  J. Parry,et al.  Serological testing algorithm shows rising HIV incidence in a UK cohort of men who have sex with men: 10 years application , 2007, AIDS.

[25]  A. Vandamme,et al.  Rising Prevalence of HIV-1 Non-B Subtypes in Belgium: 1983–2001 , 2004, Journal of acquired immune deficiency syndromes.

[26]  Roderic D. M. Page,et al.  TreeView: an application to display phylogenetic trees on personal computers , 1996, Comput. Appl. Biosci..

[27]  M. P. Cummings,et al.  PAUP* Phylogenetic analysis using parsimony (*and other methods) Version 4 , 2000 .

[28]  Michel Roger,et al.  Transmission networks of drug resistance acquired in primary/early stage HIV infection , 2008, AIDS.

[29]  Anne-Mieke Vandamme,et al.  Prevalence and epidemiology of HIV type 1 drug resistance among newly diagnosed therapy-naive patients in Belgium from 2003 to 2006. , 2008, AIDS research and human retroviruses.

[30]  Klaus Korn,et al.  Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management. , 2005, The Journal of infectious diseases.

[31]  M. Laga,et al.  Longstanding presence in Belgians of multiple non-B HIV-1 subtypes , 1996, The Lancet.

[32]  J P Bru,et al.  Acute HIV infection: impact on the spread of HIV and transmission of drug resistance , 2001, AIDS.

[33]  A. Lapedes,et al.  Timing the ancestor of the HIV-1 pandemic strains. , 2000, Science.

[34]  Anne-Mieke Vandamme,et al.  Limitations to contact tracing and phylogenetic analysis in establishing HIV type 1 transmission networks in Cuba. , 2007, AIDS research and human retroviruses.

[35]  Michel Roger,et al.  High rates of forward transmission events after acute/early HIV-1 infection. , 2007, The Journal of infectious diseases.

[36]  A. Rambaut,et al.  Episodic Sexual Transmission of HIV Revealed by Molecular Phylodynamics , 2008, PLoS medicine.

[37]  D. De Bacquer,et al.  Measuring the impact of multidrug resistance in nosocomial infection , 2007, Current opinion in infectious diseases.

[38]  Jaa Nylander,et al.  MrModeltest 2.2. Program Distributed by the Author , 2004 .

[39]  S. Osmanov,et al.  Molecular Epidemiology of HIV-1 in St Petersburg, Russia: Predominance of Subtype A, Former Soviet Union Variant, and Identification of Intrasubtype Subclusters , 2009, Journal of acquired immune deficiency syndromes.

[40]  Julie Dawn Thompson,et al.  Improved sensitivity of profile searches through the use of sequence weights and gap excision , 1994, Comput. Appl. Biosci..