title: HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania.
abstract: In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident strains revealed the emergence of CRF41_CD and many unique recombinants, as well as the presence of six local transmission networks most of which were confined to the rural subpopulation. In the context of vaccine cohort selection, these results suggest distinct infection transmission dynamics within these three geographically close subpopulations. The diversity and genetic sequences of the HIV-1 strains obtained during this study will greatly contribute to the planning, immunogen selection, and analysis of vaccine-induced immune responses observed during HIV-1 vaccine trials in Tanzania and neighboring countries.
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Erik
authors.initials: E
authors.lastname: Billings
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Eric
authors.initials: E
authors.lastname: Sanders-Buell
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Meera
authors.initials: M
authors.lastname: Bose
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Kijak
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bradfield
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Crossler
authors.affiliation: 2 United States Military HIV Research Program/Walter Reed Army Institute of Research , Silver Spring, Maryland.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Arroyo
authors.affiliation: 3 NIMR-Mbeya Medical Research Center , Mbeya, Tanzania .
authors.forename: Leonard
authors.initials: L
authors.lastname: Maboko
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.|3 NIMR-Mbeya Medical Research Center , Mbeya, Tanzania .
authors.forename: Oliver
authors.initials: O
authors.lastname: Hoffmann
authors.affiliation: 3 NIMR-Mbeya Medical Research Center , Mbeya, Tanzania .|4 Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU) , Munich, Germany .
authors.forename: Steffen
authors.initials: S
authors.lastname: Geis
authors.affiliation: 2 United States Military HIV Research Program/Walter Reed Army Institute of Research , Silver Spring, Maryland.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.affiliation: 5 International Vaccine Institute , Seoul, Republic of Korea.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 2 United States Military HIV Research Program/Walter Reed Army Institute of Research , Silver Spring, Maryland.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: 4 Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU) , Munich, Germany .|6 German Centre for Infection Research (DZIF) , Munich partner site, Munich, Germany .
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.affiliation: 1 United States Military HIV Research Program/Henry M. Jackson Foundation , Silver Spring, Maryland.
authors.forename: Sodsai
authors.initials: S
authors.lastname: Tovanabutra
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D011446:Prospective Studies; D011995:Recombination, Genetic; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D013636:Tanzania / Q000453:epidemiology; D055815:Young Adult
keywords: HIV genetics; HIV transmission; epidemiology; phylogenetics; vaccines