title: Reconstructing the HIV-1 CRF02_AG and CRF06_cpx epidemics in Burkina Faso and West Africa using early samples.
abstract: HIV-1 circulating recombinant forms (CRFs) represent viral recombinant lineages that play a significant role in the global epidemic. Two of them dominate the epidemic in Burkina Faso: CRF06_cpx (first described in this country) and CRF02_AG. We reconstructed the phylodynamics of both recombinant viruses in Burkina Faso and throughout West Africa.
  
  
  
  We analysed CRF06_cpx and CRF02_AG sequences (protease/gp41) from early samples collected in Burkina Faso in 1986 together with other GenBank sequences (1984-2013) in 4 datasets: African CRF06_cpx (210/60); down-sampled CRF06_cpx (146/45); Burkina Faso CRF02_AG (130/39) and West/Central African CRF02_AG (691/298). For each dataset, we analysed both protease and gp41 jointly using the BEAST multilocus analysis and conducted phylogeographic analysis to reconstruct the early migration routes between countries.
  
  
  
  The time to the most recent common ancestor (tMRCA) of CRF06_cpx was 1979 (1973-1983) for protease and 1981 (1978-1983) for gp41. The gp41 analysis inferred the origin of CRF06_cpx (or at least its parental subtype G lineage) in the Democratic Republic of Congo but migrated to Burkina Faso soon after (1982). Both genes showed that CRF06_cpx radiated to the rest of West Africa predominantly after around 1990. These results were robust to the oversampling of Burkina Faso sequences as they were confirmed in the down-sampled dataset. The tMRCA of the Burkina Faso CRF02_AG lineage was 1979 (1977-1983) for protease and 1980 (1978-1981) for gp41. However, we reconstructed its presence in West Africa much earlier (mid-1960s), with an initial origin in Cameroon and/or Nigeria, and its phylogeographic analysis revealed much interconnection within the region with a lack of country-specific phylogenetic patterns, which prevents tracking its exact migration routes.
  
  
  
  Burkina Faso presents a relatively young HIV epidemic, with the diversification of the current in-country CRF02_AG and CRF06_cpx lineages taking place around 1980. This country represents the main source of CRF06_cpx in West Africa. The CRF02_AG epidemic started at least a decade earlier and showed much interchange between West African countries (especially involving coastal countries) suggesting great population mobility and an extensive viral spread in the region.
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK. Electronic address: Gonzalo.Yebra@ed.ac.uk.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Yebra
authors.affiliation: Institute for Global Health, Vanderbilt University, Nashville, TN, USA.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Kalish
authors.affiliation: Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Leigh Brown
mesh_terms: D002050:Burkina Faso / Q000453:epidemiology; D030541:Databases, Genetic; D058872:Epidemics / Q000706:statistics & numerical data*; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D010802:Phylogeny; D058974:Phylogeography; D011995:Recombination, Genetic
keywords: Burkina Faso; HIV; Phylodynamics; Phylogeography; Recombinant; West Africa