title: CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.
abstract: BACKGROUND
  Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba.
  
  
  METHODS
  Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining.
  
  
  RESULTS
  Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis.
  
  
  CONCLUSIONS
  CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.
authors.affiliation: Virology Department, Institute of Tropical Medicine Pedro Kourí, Autopista Novia del Mediodía Km 6, Marianao 13, Havana City, Cuba.
authors.forename: Vivian
authors.initials: V
authors.lastname: Kouri
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium ; LIMI-LIP, Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Salvador-Bahia, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Khouri
authors.affiliation: Virology Department, Institute of Tropical Medicine Pedro Kourí, Autopista Novia del Mediodía Km 6, Marianao 13, Havana City, Cuba.
authors.forename: Yoan
authors.initials: Y
authors.lastname: Alemán
authors.affiliation: Virology Department, Institute of Tropical Medicine Pedro Kourí, Autopista Novia del Mediodía Km 6, Marianao 13, Havana City, Cuba.
authors.forename: Yeissel
authors.initials: Y
authors.lastname: Abrahantes
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercauteren
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium ; Clinical and Molecular Infectious Diseases Group, Faculty of Sciences and Mathematics, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Andrea-Clemencia
authors.initials: AC
authors.lastname: Pineda-Peña
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Theys
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Megens
authors.affiliation: AIDS Reference Center, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Moutschen
authors.affiliation: Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, 66123 Saarbrücken, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Pfeifer
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Van Weyenbergh
authors.affiliation: Virology Department, Institute of Tropical Medicine Pedro Kourí, Autopista Novia del Mediodía Km 6, Marianao 13, Havana City, Cuba.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Pérez
authors.affiliation: Virology Department, Institute of Tropical Medicine Pedro Kourí, Autopista Novia del Mediodía Km 6, Marianao 13, Havana City, Cuba.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pérez
authors.affiliation: Virology Department, Institute of Tropical Medicine Pedro Kourí, Autopista Novia del Mediodía Km 6, Marianao 13, Havana City, Cuba.
authors.forename: Lissette
authors.initials: L
authors.lastname: Pérez
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium.
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Laethem
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Clinical and Epidemiological Virology, B-3000 Leuven, Belgium ; Centro de Malária e outras Doenças Tropicais and Unidade de Microbiologia, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D000328:Adult; D005075:Biological Evolution; D060085:Coinfection; D003462:Cuba / Q000453:epidemiology; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012725:Sexual Behavior; D019562:Viral Load; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D054299:env Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus
keywords: CRF19; Cuba; HIV-1; Progression to AIDS; Variant