title: Spatiotemporal dynamics of HIV-1 transmission in France (1999-2014) and impact of targeted prevention strategies.
abstract: BACKGROUND
  Characterizing HIV-1 transmission networks can be important in understanding the evolutionary patterns and geospatial spread of the epidemic. We reconstructed the broad molecular epidemiology of HIV from individuals with primary HIV-1 infection (PHI) enrolled in France in the ANRS PRIMO C06 cohort over 15 years.
  
  
  RESULTS
  Sociodemographic, geographic, clinical, biological and pol sequence data from 1356 patients were collected between 1999 and 2014. Network analysis was performed to infer genetic relationships, i.e. clusters of transmission, between HIV-1 sequences. Bayesian coalescent-based methods were used to examine the temporal and spatial dynamics of identified clusters from different regions in France. We also evaluated the use of network information to target prevention efforts. Participants were mostly Caucasian (85.9%) and men (86.7%) who reported sex with men (MSM, 71.4%). Overall, 387 individuals (28.5%) were involved in clusters: 156 patients (11.5%) in 78 dyads and 231 participants (17%) in 42 larger clusters (median size: 4, range 3-41). Compared to individuals with single PHI (n = 969), those in clusters were more frequently men (95.9 vs 83%, p < 0.01), MSM (85.8 vs 65.6%, p < 0.01) and infected with CRF02_AG (20.4 vs 13.4%, p < 0.01). Reconstruction of viral migrations across time suggests that Paris area was the major hub of dissemination of both subtype B and CRF02_AG epidemics. By targeting clustering individuals belonging to the identified active transmission network before 2010, 60 of the 143 onward transmissions could have been prevented.
  
  
  CONCLUSIONS
  These analyses support the hypothesis of a recent and rapid rise of CRF02_AG within the French HIV-1 epidemic among MSM. Combined with a short turnaround time for sample processing, targeting prevention efforts based on phylogenetic monitoring may be an efficient way to deliver prevention interventions but would require near real time targeted interventions on the identified index cases and their partners.
authors.affiliation: University of California, San Diego, 9500 Gilman Drive, Stein Clinical Research Building #325, La Jolla, CA, 92093-0697, USA. achaillon@ucsd.edu.
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaillon
authors.affiliation: INSERM CESP U1018, University Paris Sud, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (APHP), Le Kremlin-Bicêtre, France.
authors.forename: Asma
authors.initials: A
authors.lastname: Essat
authors.affiliation: EA7327, Université Paris Descartes, Paris, France.|Laboratoire de Microbiologie Clinique, Hôpital Necker - Enfants Malades, APHP, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.affiliation: University of California, San Diego, 9500 Gilman Drive, Stein Clinical Research Building #325, La Jolla, CA, 92093-0697, USA.|Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: INSERM U941, Laboratoire de Virologie, Université Paris Diderot, Hôpital Saint-Louis, AP-HP, CNR VIH associé Primo infection, Paris, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.affiliation: INSERM U966 and National Reference Center for HIV, CHU Bretonneau and Université François Rabelais, Tours, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Barin
authors.affiliation: EA7327, Université Paris Descartes, Paris, France.|UF de Thérapeutique en Immuno-Infectiologie, Hôpital Hôtel Dieu, APHP, Paris, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Tenon, APHP, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.affiliation: Service Universitaire des Maladies infectieuses et du Voyageur, Centre Hospitalier de Tourcoing, Tourcoing, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Robineau
authors.affiliation: EA7327, Université Paris Descartes, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.affiliation: INSERM CESP U1018, University Paris Sud, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (APHP), Le Kremlin-Bicêtre, France.|Service de Médecine interne et Immunologie clinique, Hôpital Bicêtre, APHP, Le Kremlin-Bicêtre, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.affiliation: INSERM CESP U1018, University Paris Sud, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (APHP), Le Kremlin-Bicêtre, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: INSERM U941, Laboratoire de Virologie, Université Paris Diderot, Hôpital Saint-Louis, AP-HP, CNR VIH associé Primo infection, Paris, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D005260:Female; D005602:France / Q000453:epidemiology; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D017422:Sequence Analysis, DNA; D062211:Spatio-Temporal Analysis; D055815:Young Adult; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054302:pol Gene Products, Human Immunodeficiency Virus
keywords: HIV-1; Phylogeography; Primary infection; Transmission network; Treatment as prevention