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      Transmission Network Parameters Estimated From HIV Sequences for a Nationwide Epidemic

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          Abstract

          Background.  Many studies of sexual behavior have shown that individuals vary greatly in their number of sexual partners over time, but it has proved difficult to obtain parameter estimates relating to the dynamics of human immunodeficiency virus (HIV) transmission except in small-scale contact tracing studies. Recent developments in molecular phylodynamics have provided new routes to obtain these parameter estimates, and current clinical practice provides suitable data for entire infected populations.

          Methods.  A phylodynamic analysis was performed on partial pol gene sequences obtained for routine clinical care from 14 560 individuals, representing approximately 60% of the HIV-positive men who have sex with men (MSM) under care in the United Kingdom.

          Results.  Among individuals linked to others in the data set, 29% are linked to only 1 individual, 41% are linked to 2–10 individuals, and 29% are linked to ≥10 individuals. The right-skewed degree distribution can be approximated by a power law, but the data are best fitted by a Waring distribution for all time depths. For time depths of 5–7 years, the distribution parameter ρ lies within the range that indicates infinite variance.

          Conclusions.  The transmission network among UK MSM is characterized by preferential association such that a randomly distributed intervention would not be expected to stop the epidemic.

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          Dating of the human-ape splitting by a molecular clock of mitochondrial DNA.

          H Kishino, T Yano, M. Hasegawa (1984)
          A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed. This method takes into account effectively the information contained in a set of DNA sequence data. The molecular clock of mitochondrial DNA (mtDNA) was calibrated by setting the date of divergence between primates and ungulates at the Cretaceous-Tertiary boundary (65 million years ago), when the extinction of dinosaurs occurred. A generalized least-squares method was applied in fitting a model to mtDNA sequence data, and the clock gave dates of 92.3 +/- 11.7, 13.3 +/- 1.5, 10.9 +/- 1.2, 3.7 +/- 0.6, and 2.7 +/- 0.6 million years ago (where the second of each pair of numbers is the standard deviation) for the separation of mouse, gibbon, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. Although there is some uncertainty in the clock, this dating may pose a problem for the widely believed hypothesis that the pipedal creature Australopithecus afarensis, which lived some 3.7 million years ago at Laetoli in Tanzania and at Hadar in Ethiopia, was ancestral to man and evolved after the human-ape splitting. Another likelier possibility is that mtDNA was transferred through hybridization between a proto-human and a proto-chimpanzee after the former had developed bipedalism.
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            R: a language and environment for statistic computing

            R.D.C. Team, R Development Core Team, RDC Team … (2008)
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              Molecular epidemiology reveals long-term changes in HIV type 1 subtype B transmission in Switzerland.

              P Vernazza, Rainer Weber, Matthias Cavassini … (2010)
              Sequence data from resistance testing offer unique opportunities to characterize the structure of human immunodeficiency virus (HIV) infection epidemics. We analyzed a representative set of HIV type 1 (HIV-1) subtype B pol sequences from 5700 patients enrolled in the Swiss HIV Cohort Study. We pooled these sequences with the same number of sequences from foreign epidemics, inferred a phylogeny, and identified Swiss transmission clusters as clades having a minimal size of 10 and containing >or=80% Swiss sequences. More than one-half of Swiss patients were included within 60 transmission clusters. Most transmission clusters were significantly dominated by specific transmission routes, which were used to identify the following patient groups: men having sex with men (MSM) (38 transmission clusters; average cluster size, 29 patients) or patients acquiring HIV through heterosexual contact (HETs) and injection drug users (IDUs) (12 transmission clusters; average cluster size, 144 patients). Interestingly, there were no transmission clusters dominated by sequences from HETs only. Although 44% of all HETs who were infected between 1983 and 1986 clustered with injection drug users, this percentage decreased to 18% for 2003-2006 (P<.001), indicating a diminishing role of injection drug users in transmission among HETs over time. Our analysis suggests (1) the absence of a self-sustaining epidemic of HIV-1 subtype B in HETs in Switzerland and (2) a temporally decreasing clustering of HIV infections in HETs and IDUs.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Infect Dis
                Journal ID (hwp): jinfdis
                Journal ID (publisher-id): jinfdis
                Title: The Journal of Infectious Diseases
                Publisher: Oxford University Press
                ISSN (Print): 0022-1899
                ISSN (Electronic): 1537-6613
                Publication date (Print): 01 November 2011
                Publication date PMC-release: 01 November 2011
                Volume: 204
                Issue: 9
                Pages: 1463-1469
                Affiliations
                [1 ]Institute of Evolutionary Biology, University of Edinburgh
                [2 ]Medical Research Council Clinical Trials Unit, London, United Kingdom
                Author notes
                Correspondence: Andrew J. Leigh Brown, PhD, University of Edinburgh, Ashworth Bldg, W Mains Rd, Edinburgh EH9 3JT, United Kingdom ( a.leigh-brown@ 123456ed.ac.uk ).

                Presented in part: 17th HIV Dynamics and Evolution Conference, Pacific Grove, California, April 2010.

                [a]

                Present affiliation: Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom (L. W.); Health Protection Agency, Cambridge, United Kingdom (G. J. H.).

                Article
                DOI: 10.1093/infdis/jir550
                PMC ID: 3182313
                PubMed ID: 21921202
                SO-VID: 9ff0cbc1-af81-4336-815a-cfdd212f986c
                Copyright © © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 7 February 2011
                Date accepted : 20 June 2011
                Categories
                Subject: Major Articles and Brief Reports
                Subject: HIV/AIDS

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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