title: Molecular evolution of the HIV-1 Thai epidemic between the time of RV144 immunogen selection to the execution of the vaccine efficacy trial.
abstract: The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results.
authors.affiliation: U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA. gkijak@hivresearch.org
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Kijak
authors.forename: Sodsai
authors.initials: S
authors.lastname: Tovanabutra
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.forename: Chirapa
authors.initials: C
authors.lastname: Eamsila
authors.forename: Prayura
authors.initials: P
authors.lastname: Kunasol
authors.forename: Chirasak
authors.initials: C
authors.lastname: Khamboonruang
authors.forename: Prasert
authors.initials: P
authors.lastname: Thongcharoen
authors.forename: Chawetsan
authors.initials: C
authors.lastname: Namwat
authors.forename: Nakorn
authors.initials: N
authors.lastname: Premsri
authors.forename: Michael
authors.initials: M
authors.lastname: Benenson
authors.forename: Patricia
authors.initials: P
authors.lastname: Morgan
authors.forename: Meera
authors.initials: M
authors.lastname: Bose
authors.forename: Eric
authors.initials: E
authors.lastname: Sanders-Buell
authors.forename: Robert
authors.initials: R
authors.lastname: Paris
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Birx
authors.forename: Mark S
authors.initials: MS
authors.lastname: De Souza
authors.forename: Francine E
authors.initials: FE
authors.lastname: McCutchan
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D001483:Base Sequence; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005434:Flow Cytometry; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013785:Thailand / Q000453:epidemiology; D014765:Viral Vaccines / Q000235:genetics
chemical_list: D014765:Viral Vaccines