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Swiss Cohort Analysis Reveals Clusters of Transmitted Resistant HIV:
"make sure patient names remain unlinked to transmission analyses"
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Mark Mascolini
XVIII International Drug Resistance Workshop, June 9-13, 2009, Fort Myers, Florida
Phylogenetic analysis of HIV sequences from gay men in Switzerland determined that almost one third of transmitted drug resistance could be attributed to transmission from recently infected people [1]. About 10% of all transmitted resistance mutations appeared to come from a chronically infected person.
Viktor von Wyl and Swiss HIV Cohort Study (SHCS) colleagues set out to estimate how many new HIV infections with resistant virus could be attributed to recently infected people and how many could be linked to antiretroviral-exposed chronically infected people among gay men in German-speaking Switzerland. From the SHCS database of HIV pol sequences, they selected 430 subtype B sequences from gay or bisexual men with an estimated year of infection between 2001 and 2004. They used the remaining 2382 sequences from gay men as controls.
The investigators defined HIV transmission clusters as branches in a neighbor-joining tree with at least two sequences, of which at least one sequence was among the 430 tracked sequences and had a bootstrap value of at least 98/100. This process yielded 218 tracked sequences (51% of 430) and 206 control sequences (9% of 2382).
Among tracked sequences, 39 of 218 (18%) carried at least one drug resistance mutation, as defined on the 2009 World Health Organization list [2]. Twenty of those 39 tracked sequences (51%) belonged to transmission clusters. Twelve of 39 tracked sequences with resistant virus (31%) fell into 6 clusters involving onward transmission among recently infected people. Four of 39 tracked sequences with resistant virus (10%) fell into 4 clusters with an antiretroviral-exposed chronically infected transmission source. With the remaining 23 tracked sequences (59%), the source could not be determined.
Von Wyl's report stimulated lively discussion at the workshop about the legal ramifications of sequence linking by phylogenetic analysis. Anne-Mieke Vandamme from Leuven's Rega Institute for Medical Research cautioned all colleagues working in this area to make sure patient names remain unlinked to transmission analyses. Otherwise such data may be commandeered by attorneys for people suing others for infecting them with HIV.
Phylogenetic analysis can identify HIV transmission clusters, but it cannot determine which individual in a cluster infected another person in that cluster. Nevertheless, Vandamme noted, "expert witnesses" regularly cite phylogenetic analysis as "proof" that a defendant has infected a plaintiff. In the SHCS, HIV sequences are anonymous and are linked to cohort data by a study ID number.
References
1. von Wyl V, Yerly S, Boni J, et al. Successful identification of sources of transmitted drug-resistant HIV-1 via a cross-sectional phylogenetic analysis. XVIII International Drug Resistance Workshop. June 9-13, 2009. Fort Myers, Florida. Abstract 39.
2. Bennett DE, Camacho RJ, Otelea D, et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PLoS One. 2009;4(3):e4724.
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