title: Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus.
abstract: The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scandinavian population) and a rapid disease course. His HIV V3 region contained genotypic features attributable to X4 virus and resembled functionally verified X4 virus and virus from patients treated with a CD4 cell-stimulating drug, tucaresol. Age-related differences in disease progression rate and survival time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors.
authors.affiliation: Department of Medical Microbiology and Immunology, Arhus University School of Medicine, Denmark. aifrhm@inet.uni2.dk
authors.forename: Astrid K N
authors.initials: AK
authors.lastname: Iversen
authors.forename: Claus Bohn
authors.initials: CB
authors.lastname: Christiansen
authors.forename: Jørn
authors.initials: J
authors.lastname: Attermann
authors.forename: Jesper
authors.initials: J
authors.lastname: Eugen-Olsen
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.forename: Erik
authors.initials: E
authors.lastname: Berntorp
authors.forename: Jørgen
authors.initials: J
authors.lastname: Ingerslev
authors.forename: Lars
authors.initials: L
authors.lastname: Fugger
authors.forename: Elma
authors.initials: E
authors.lastname: Scheibel
authors.forename: Lillian
authors.initials: L
authors.lastname: Tengborn
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Ebbe
authors.initials: E
authors.lastname: Dickmeiss
authors.forename: Arne
authors.initials: A
authors.lastname: Svejgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Skinhøj
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000150:complications / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006678:HIV / Q000145:classification* / Q000302:isolation & purification / Q000502:physiology; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D006467:Hemophilia A / Q000150:complications* / Q000235:genetics; D002836:Hemophilia B / Q000150:complications* / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000737:chemistry / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D019713:Receptors, CCR5