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Session 60 Poster Abstracts
HIV Diversity and Evolution during Primary Infection
Thursday, 1:30 - 3:30 pm
Hall D


291    
Genetic Viral Evolution in Patients Included in Clusters at Primary Infection
Sabine Yerly*1, H Gunthard2, M Cavassini3, J P Chave4, P Schmid5, H Furrer6, V Schiffer7, and L Perrin1
1Geneva Univ Hosp, Switzerland; 2Zurich Univ Hosp, Switzerland; 3Univ Hosp, Lausanne, Switzerland; 4Univ Hosp, Lausanne, Switzerland; 5St Gallen Hospital, Switzerland; 6Berne Univ Hosp, Switzerland; and 7Geneva Univ Hosp, Switzerland

Background:  We have previously shown by phylogenetic analyses that about 30% of the RT and PR sequences of recently infected patients segregate into clusters. We assessed sequence changes over time in these patients.

Methods:  We identified 34 patients included in 14 clusters (2 to 6 patients each) with a bootstrap value > 98% at the time of acute infection and with available plasma sample with HIV RNA > 1000 copies/mL after at least 1 year of follow-up. Population-based sequencing of RT and PR regions was performed at baseline and on the last available samples. Phylogenetic analyses were performed by neighbor joining and Fitch-Margoliash methods, and robustness of the trees were evaluated by bootstrap analysis.

Results:  The median follow-up was 29 months (12 to 83). During part of the follow-up, 12 patients received HAART, and 3 patients developed 1 major resistance mutation (103N, 184V, 181C) (these mutations were excluded in the analysis). The bootstrap values at follow-up remained > 98 of 100 within all clusters except 1. Synonymous and non-synonymous changes were correlated (R = 0.83, p > 0.001). Overall the median nucleotide change (RT + PR) was 0.25% per year (range, 0 to 2.37) and the median amino acid change was 0.39% per year (range, 0 to 2.22). Sequence variations were not dependent of the initial sequence, since differences in nucleotide changes within a cluster were higher than the median of 0.25% nucleotide change per year for 7 clusters. An example of such different evolution among members of the same cluster was observed in a cluster of 4 untreated patients with respectively 2.37, 0.33, 0.12, and 0.06% nucleotide change per year. The most frequent amino acid changes, observed in at least 10% of patients, were at positions 135, 177, and 211 for RT and 35, 36, 41, and 72 for PR.

Conclusions:  After years of follow-up, RT and PR sequences from PHI patients infected by the same strains still form clusters with bootstrap values > 98% despite within-individual evolution. Amino acid changes occurred preferentially at defined RT and PR positions. Changes were host dependent and not related to viral strain.

 

 

Keywords: primary HIV infection; viral evolution; pol gene