Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Authors

Gustavo H. Kijak, Walter Reed Army Institute of ResearchFollow
Sodsai Tovanabutra, Walter Reed Army Institute of Research
Supachai Rerks-Ngarm, Ministry of Public Health
Sorachai Nitayaphan, Armed Forces Research Institute of Medical Sciences
Chirapa Eamsila, Armed Forces Research Institute of Medical Sciences
Prayura Kunasol, Ministry of Public Health
Chirasak Khamboonruang, Ministry of Public Health
Prasert Thongcharoen, Ministry of Public Health
Chawetsan Namwat, Ministry of Public Health
Nakorn Premsri, Ministry of Public Health
Michael Benenson, Armed Forces Research Institute of Medical Sciences
Patricia Morgan, Armed Forces Research Institute of Medical Sciences
Meera Bose, Walter Reed Army Institute of Research
Eric Sanders-Buell, Walter Reed Army Institute of Research
Robert Paris, Armed Forces Research Institute of Medical Sciences
Merlin L. Robb, Walter Reed Army Institute of Research
Deborah L. Birx, Walter Reed Army Institute of Research
Mark S. De Souza, Armed Forces Research Institute of Medical Sciences
Francine E. McCutchan, Walter Reed Army Institute of Research
Nelson L. Michael, Walter Reed Army Institute of Research
Jerome H. Kim, Walter Reed Army Institute of ResearchFollow

Date of this Version

2013

Citation

Published in Journal of Virology (2013) 87(13): p. 7265-7281. DOI:10.1128/JVI.03070-12

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.