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MBE Advance Access published online on October 28, 2009
Molecular Biology and Evolution, doi:10.1093/molbev/msp254
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© 2009 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Research Article

Phylodynamics of HIV-1 from a Phase III AIDS vaccine trial in North America

Marcos Pérez-Losada*,{dagger}, David V. Jobes§, Faruk Sinangil{ddagger}, Keith A. Crandall||, David Posada and Phillip W. Berman**

{dagger} CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661 Vairão, Portugal
§ Presidio Pharmaceuticals, Inc., San Francisco, CA 94158, USA
{ddagger} Global Solutions for Infectious Diseases, Brisbane, CA 94005, USA
|| Department of Biology, Brigham Young University, Provo, UT 84602, USA
Departamento de Bioquímica, Genética e Inmunología, Universidad de Vigo, 36310 Vigo, Spain
** Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA

* Corresponding author: Marcos Pérez-Losada, CIBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485-661 Vairão, Portugal, Email: mlosada{at}genoma-llc.com

Received for publication September 15, 2009. Accepted for publication October 11, 2009.

In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from North America and the Netherlands. A total of 368 individuals became infected with HIV-1 during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced from clinical samples taken as close as possible to the time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America and 15 from the Netherlands). Here, we used these data in combination with other sequences available in public databases to assess HIV-1 variation as a function of vaccination treatment, geographic region, race, risk behavior, and viral load. Viral samples did not show any phylogenetic structure for any of these factors, but individuals with different viral loads showed significant differences (P = 0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B in USA was around 1966-1970. Despite the fact that the number of AIDS cases has decreased in North America since the early nineties, HIV-1 genetic diversity seems to have remained almost constant over time. This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines.

Key Words: America • demographics • gp120 • HIV-1 • vaccine trial


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