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16th International HIV Drug Resistance Workshop


12-16 June 2007, Barbados


A LONGITUDINAL MOLECULAR ANALYSIS OF PRIMARY HIV DRUG RESISTANCE

Antivir Ther. 2007; 12:S48 (abstract no. 41)

J Brooks 1, H Merks1, N Masse1, R Pilon1, G Jayaraman2, N Goedhuis2, C Archibald2, M Reckart3 and P Sandstrom1
1National HIV & Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Canada; 2Surveillance and Risk Assessment Division, Public Health Agency of Canada, Ottawa, Canada; 3British Columbia Centre for Disease Control, British Columbia, Canada


OBJECTIVE: Transmitted drug resistant HIV presents a barrier to effective empiric therapy of HIV infections and limits future therapeutic options for those newly infected. Identification of transmission patterns of HIV drug resistance (DR) may facilitate targeted public health interventions. Here, we describe the application of molecular epidemiology to a national surveillance program in order to more closely examine HIV DR transmission patterns.

METHODS: The Canadian HIV Strain and Drug Resistance Surveillance Program (CHSDRSP) collects and genotypes specimens from first time diagnosed, drugnaïve, HIV-infected individuals. Analysed specimens were collected in the years 2002–2004 from within a single Canadian province. The pol gene was amplified, sequenced and DR determined according to the Stanford HIVDB Calibrated Population Resistance tool. Sequences from 798 B-clade viruses were phylogenetically analysed for their relatedness to other specimens using neighbourjoining analysis (K-2-P) as implemented in MEGA 3.1. Specimens from 2002 were categorized as having DR and/or belonging to a phylogenetically linked cluster. The entire group of specimens from 2002–2004 was reanalysed and the members of the 2002 clusters with DR were re-evaluated for their membership in a cluster.

RESULTS: Within the 2002 cohort (n=296), DR was present in 9.0% (10/111) specimens that were part of clusters and in 9.7% (18/185) of specimens not found in clusters. However, within the combined 2002–2004 cohort, 50% of the 2002 clusters with DR were found to contain new related DR sequences. Only 17% of the isolated 2002 DR sequences became associated with other DR sequences. Furthermore, the cluster size, regardless of DR status, was positively correlated with more future related infections per member of the initial cluster.

CONCLUSIONS: Not only do clusters with DR persist over time, but new members to the cluster are more likely to have related DR patterns. Larger clusters are associated with more related infections over time. Targeting public health interventions toward clusters of related infections would identify a greater percentage of transmitted DR, and may have a much greater impact overall in reducing HIV transmission.

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2007-06-12
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