title: HIV-1 envelope diversity 1 year after seroconversion predicts subsequent disease progression.
abstract: OBJECTIVE
  Recent studies have suggested that the dynamics of HIV-1 evolutionary rate reflect the rate of disease progression. We wished to determine whether viral diversity early in infection is predictive of the subsequent disease course.
  
  
  METHODS
  HIV-1 envelope diversity at seroconversion and 1 year thereafter from 89 homosexual participants of the Amsterdam Cohort Studies on HIV infection and AIDS was correlated with clinical endpoints and markers of disease progression.
  
  
  METHODS
  Heteroduplex mobility assay (HMA) and sequencing followed by calculation of pairwise genetic distances were applied to determine HIV-1 envelope diversity. The HMA pattern (presence or absence of heteroduplexes) and sequence diversity were each tested for correlation with the clinical course of infection.
  
  
  RESULTS
  HMA pattern at 1-year postseroconversion was significantly associated with progression to AIDS and AIDS-related death, with presence of heteroduplexes associated with accelerated disease progression. Moreover, not only this dichotomous measure of viral diversity (absence or presence of heteroduplexes), but also genetic diversity itself was associated with disease course. HMA pattern was an independent predictor of accelerated disease progression, also when CCR5 genotype, human leukocyte antigen (HLA)-type, viral load, CD4 T-cell counts, and coreceptor use at viral load set point were included in the analysis.
  
  
  CONCLUSIONS
  Viral diversity early in HIV-1 infection is predictive of the subsequent disease progression. It remains to be established whether viral diversity itself plays a causal role in the increased damage to the immune system or whether it is a reflection of immune pressure or other selective forces.
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rachinger
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.forename: Esther F
authors.initials: EF
authors.lastname: Gijsbers
authors.forename: Tom L G M
authors.initials: TL
authors.lastname: van den Kerkhof
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Angélique B
authors.initials: AB
authors.lastname: van 't Wout
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000401:mortality / Q000821:virology; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes; D018450:Disease Progression; D015658:HIV Infections / Q000235:genetics / Q000821:virology*; D006679:HIV Seropositivity / Q000235:genetics / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D020180:Heteroduplex Analysis; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000276:immunology; D019713:Receptors, CCR5 / Q000276:immunology; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000235:genetics*; D019562:Viral Load
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D012367:RNA, Viral; D019713:Receptors, CCR5; D014759:Viral Envelope Proteins