Longitudinal population analysis of dual infection with recombination in two strains of HIV type 1 subtype B in an individual from a Phase 3 HIV vaccine efficacy trial.
This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development.
Jobes
David V
DV
VaxGen, Inc., South San Francisco, California 94080, USA. david@presidiopharma.com
Daoust
Melissa
M
Nguyen
Vivian T
VT
Padua
Allan
A
Sinangil
Faruk
F
Pérez-Losada
Marcos
M
Crandall
Keith A
KA
Oliphant
Theodore
T
Posada
David
D
Rambaut
Andrew
A
Fuchs
Jonathan
J
Berman
Phillip W
PW
D016915:AIDS Vaccines; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic
D016915:AIDS Vaccines