title: Molecular epidemiology of human immunodeficiency virus type 1 transmission in a heterosexual cohort of discordant couples in Zambia.
abstract: Most human immunodeficiency virus type 1 (HIV-1) transmissions in sub-Saharan Africa are believed to occur between married adults who are discordant for their HIV-1 infection status; however, no studies to date have investigated the molecular epidemiology of such transmission events. Here we report the genetic characterization of HIV-1 strains from 149 transmission pairs that were identified prospectively in a cohort of discordant couples in Lusaka, Zambia. Subgenomic gag, gp120, gp41, and/or long terminal repeat regions were amplified by PCR analysis of uncultured blood samples from both partners and sequenced without interim cloning. Pairwise genetic distances were calculated for the regions analyzed and compared to those of subtype-specific reference sequences as well as local controls. Sequence relationships were also examined by phylogenetic tree analysis. By these approaches, epidemiological linkage was established for the majority of transmission pairs. Viruses from 129 of the 149 couples (87%) were very closely related and clustered together in phylogenetic trees in a statistically highly significant manner. In contrast, viruses from 20 of the 149 couples (13%) were only distantly related in two independent genomic regions, thus ruling out transmission between the two partners. The great majority (95%) of transmitted viruses were of subtype C origin, although representatives of subtypes A, D, G, and J were also identified. There was no evidence for extensive transmission networks within the cohort, although two phylogenetic subclusters of viruses infecting two couples each were identified. Taken together, these data indicate that molecular epidemiological analyses of presumed transmission pairs are both feasible and required to determine behavioral, virological, and immunological correlates of heterosexual transmission in sub-Saharan Africa with a high level of accuracy.
authors.affiliation: Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Trask
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.forename: Ulgen
authors.initials: U
authors.lastname: Fideli
authors.forename: Yalu
authors.initials: Y
authors.lastname: Chen
authors.forename: Sreelatha
authors.initials: S
authors.lastname: Meleth
authors.forename: Francis
authors.initials: F
authors.lastname: Kasolo
authors.forename: Rosemary
authors.initials: R
authors.lastname: Musonda
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
mesh_terms: D015331:Cohort Studies; D005195:Family Relations; D015658:HIV Infections / Q000453:epidemiology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D020010:Heterosexuality; D006801:Humans; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D015024:Zambia / Q000453:epidemiology
chemical_list: D012367:RNA, Viral