Estimating Number of Founder Lineages and Infection Duration of Multivariant HIV-1 Transmissions

• Activity Number: 413
• Type: Topic Contributed
• Date/Time: Tuesday, August 2, 2016 : 2:00 PM to 3:50 PM
• Sponsor: Health Policy Statistics Section
• Author(s): Tanzy Love* and Sung Yong Park and Elena E. Giorgi and Wendy Mack and Alan S. Perelson and Ha Youn Lee
• Companies: University of Rochester and University of Southern California and Los Alamos National Laboratory and University of Southern California and Los Alamos National Laboratory and University of Southern California
• Keywords: mixture models ; hamming distance ; Poisson ; genetic diversity

Abstract

Characterizing HIV-1 transmission and early evolution is important for developing effective vaccination and prevention strategies. Simultaneous infections by multiple HIV-1 strains can lead to early genetic diversity as high as that of a long-standing infection. Here we develop a mixture model for early HIV-1 evolution within a subject whose infection originates from multiple viral variants. We assume that pairwise base pair differences between viruses are exchangeable and come from a mixture of Poisson distributions shifted by an initial difference of that pair's founder sequences. Using Bayes and Empirical Bayes estimation, we find the most likely number of founders in the virus population and estimate the base pair differences between them at the time of infection. With published HIV-1 full envelope sequence data, our model identified 20 cases of multivariant transmissions out of 92 in heterosexuals, with a mean of 2.8 founder viral variants. Consistent with previous reports, both men who have sex with men and intravenous drug user groups show a much higher frequency of multivariant transmissions. Our model provides a principled approach to understanding early genetic diversity.