title: Origin, imports and exports of HIV-1 subtype C in South Africa: A historical perspective.
abstract: While the HIV epidemic in South Africa had a later onset than epidemics in other southern African countries, prevalence grew rapidly during the 1990's when the country was going through socio-political changes with the end of Apartheid. South Africa currently has the largest number of people living with HIV in the world and the epidemic is dominated by a unique subtype, HIV-1 subtype C. This large epidemic is also characterized by high level of genetic diversity. We hypothesize that this diversity is due to multiple introductions of the virus during the period of change. In this paper, we apply novel phylogeographic methods to estimate the number of viral imports and exports from the start of the epidemic to the present.
  
  
  
  We assembled 11,289 unique subtype C pol sequences from southern Africa. These represent one of the largest sequence datasets ever analyzed in the region. Sequences were stratified based on country of sampling and levels of genetic diversity were estimated for each country. Sequences were aligned and a maximum-likelihood evolutionary tree was inferred. Least-Squares Dating was then used to obtain a dated phylogeny from which we estimated the number of introductions into and exports out of South Africa using parsimony-based ancestral location reconstructions.
  
  
  
  Our results identified 189 viral introductions into South Africa with the largest number of introductions attributed to Zambia (n=109), Botswana (n=32), Malawi (n=26) and Zimbabwe (n=13). South Africa also exported many viral lineages to its neighbours. The bulk viral imports and exports appear to have occurred between 1985 and 2000, coincident with the period of socio-political transition.
  
  
  
  The high level of subtype C genetic diversity in South Africa is related to multiple introductions of the virus to the country. While the number of viral imports and exports we identified was highly sensitive to the number of samples included from each country, they mostly clustered around the period of rapid political and socio-economic change in South Africa.
authors.affiliation: Africa Centre for Population Health, University of KwaZulu-Natal, Durban 4041, South Africa. Electronic address: ewilkinson83@gmail.com.
authors.forename: Eduan
authors.initials: E
authors.lastname: Wilkinson
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland. Electronic address: david.rasmussen@bsse.ethz.ch.
authors.forename: David
authors.initials: D
authors.lastname: Rasmussen
authors.affiliation: Imperial College London, School of Public Health, Department of Infectious Disease Epidemiology, London W2 1PG, United Kingdom. Electronic address: oliver.ratmann@imperial.ac.uk.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ratmann
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland. Electronic address: tanja.stadler@bsse.ethz.ch.
authors.forename: Tanja
authors.initials: T
authors.lastname: Stadler
authors.affiliation: Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Western Cape Province 7505, South Africa; National Health Laboratory Services (NHLS), Tygerberg Coastal, Cape Town, 8000, South Africa. Electronic address: susanen@sun.ac.za.
authors.forename: Susan
authors.initials: S
authors.lastname: Engelbrecht
authors.affiliation: Africa Centre for Population Health, University of KwaZulu-Natal, Durban 4041, South Africa; College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa; Research Department of Infection, University College London, London WC1E 6BT, United Kingdom. Electronic address: tuliodna@gmail.com.
authors.forename: Tulio
authors.initials: T
authors.lastname: de Oliveira
mesh_terms: D030541:Databases, Genetic; D014644:Genetic Variation / Q000235:genetics; D015658:HIV Infections / Q000453:epidemiology / Q000266:history / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D010802:Phylogeny; D058974:Phylogeography; D013019:South Africa / Q000453:epidemiology
keywords: Genetic diversity; HIV-1 subtype C; Phylogeographic; South Africa; Viral exports; Viral imports