title: Mortality among human immunodeficiency virus type 2-positive villagers in rural Guinea-Bissau is correlated with viral genotype.
abstract: We present the results of a 6-year study of 131 human immunodeficiency virus (HIV) type 2 (HIV-2)-infected individuals from a rural population in Guinea-Bissau. Proviral DNA sequences 1.3 kb in length were obtained from each individual and, together with clinical data, including proviral load and CD4 and CD8 levels, were used to assess whether viral genotype influences clinical outcome. With a phylogenetic model, a correlation was found between viral genotype and mortality; this correlation was not due to confounding factors, such as age-specific viral strains or cohabitation of patients. The data provide strong evidence for the involvement of viral genetic factors in determining HIV disease progression in vivo. The pattern of association found suggests that virulence factors are multiple and scattered throughout the HIV-2 genome and can be rapidly gained or lost by the virus through a combination of mutation and recombination. These findings may lead to the identification of viral determinants of HIV disease progression.
authors.affiliation: Wellcome Trust Centre for the Epidemiology of Infectious Diseases, Department of Zoology, University of Oxford, Oxford, United Kingdom. nicholas.grassly@zoo.ox.ac.uk
authors.forename: N C
authors.initials: NC
authors.lastname: Grassly
authors.forename: Z
authors.initials: Z
authors.lastname: Xiang
authors.forename: K
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: P
authors.initials: P
authors.lastname: Aaby
authors.forename: H
authors.initials: H
authors.lastname: Jensen
authors.forename: M
authors.initials: M
authors.lastname: Schim van der Loeff
authors.forename: F
authors.initials: F
authors.lastname: Dias
authors.forename: H
authors.initials: H
authors.lastname: Whittle
authors.forename: J
authors.initials: J
authors.lastname: Breuer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D004279:DNA, Viral; D005838:Genotype; D006169:Guinea-Bissau; D015658:HIV Infections / Q000401:mortality* / Q000821:virology; D015498:HIV-2 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D012424:Rural Population
chemical_list: D017931:DNA Primers; D004279:DNA, Viral