Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis

• DOI: 10.1038/s41467-019-09139-4
• Publication Date: 2019-03-29T11:03:19Z
• Authors: Oliver Ratmann; M. Kate Grabowski; Matthew Hall; Tanya Golubchik; Chris Wymant; Lucie Abeler-Dörner; David Bonsall; Anne Hoppe; Andrew Leigh Brown; Tulio de Oliveira; Astrid Gall; Paul Kellam; Deenan Pillay; Joseph Kagaayi; Godfrey Kigozi; Thomas C. Quinn; Maria J. Wawer; Oliver Laeyendecker; David Serwadda; Ronald H. Gray; Christophe Fraser; ; Helen Ayles; Rory Bowden; Vincent Calvez; Myron Cohen; Ann Dennis; Max Essex; Sarah Fidler; Daniel Frampton; Richard Hayes; Joshua T. Herbeck; Pontiano Kaleebu; Cissy Kityo; Jairam Lingappa; Vladimir Novitsky; Nick Paton; Andrew Rambaut; Janet Seeley; Deogratius Ssemwanga; Frank Tanser; Gertrude Nakigozi; Robert Ssekubugu; Fred Nalugoda; Tom Lutalo; Ronald Galiwango; Fred Makumbi; Nelson K. Sewankambo; Aaron A. R. Tobian; Steven J. Reynolds; Larry W. Chang; Dorean Nabukalu; Anthony Ndyanabo; Joseph Ssekasanvu; Hadijja Nakawooya; Jessica Nakukumba; Grace N. Kigozi; Betty S. Nantume; Nampijja Resty; Jedidah Kambasu; Margaret Nalugemwa; Regina Nakabuye; Lawrence Ssebanobe; Justine Nankinga; Adrian Kayiira; Gorreth Nanfuka; Ruth Ahimbisibwe; Stephen Tomusange; Ronald M. Galiwango; Sarah Kalibbali; Margaret Nakalanzi; Joseph Ouma Otobi; Denis Ankunda; Joseph Lister Sse...; John Baptist Ssem...; Robert Kairania; Emmanuel Kato; Alice Kisakye; James Batte; James Ludigo; Abisagi Nampijja; Steven Watya; Kighoma Nehemia; Margaret Anyokot; Joshua Mwinike; George Kibumba; Paschal Ssebowa; George Mondo; Francis Wasswa; Agnes Nantongo; Rebecca Kakembo; Josephine Galiwango; Geoffrey Ssemango; Andrew D. Redd; John Santelli; Caitlin E. Kennedy; Jennifer Wagman
• Keywords: Adult; 0301 basic medicine; Adolescent; Science; 610; HIV Infections; Article; Young Adult; 03 medical and health sciences; 616; MD Multidisciplinary; 2.2 Factors relating to the physical environment; Humans; Aetiology; Epidemics; Phylogeny; Biomedical and Clinical Sciences; Base Sequence; software; Research; Prevention; Q; High-Throughput Nucleotide Sequencing; Middle Aged; ethics; 3. Good health; Phylogenetics; Infectious Diseases; Good Health and Well Being; Medical Microbiology; Legacy; Africa; HIV-1; HIV/AIDS; PANGEA Consortium and Rakai Health Sciences Program; Infection; 2.4 Surveillance and distribution; HIV infections

AbstractTo prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these ‘source’ populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8–28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa.