Local phylogenetic analysis identifies distinct trends in transmitted HIV drug resistance: implications for public health interventions

James I Brooks,Harriet Merks,Harrison Niznick,Jonathan B Angel,Marianna Ofner

doi:10.1186/1471-2334-13-509

Abstract

BackgroundHIV transmitted drug resistance (TDR) surveillance is usually conducted by sampling from a large population. However, overall TDR prevalence results may be inaccurate for many individual clinical setting. We analyzed HIV genotypes at a tertiary care setting in Ottawa, Ontario in order to evaluate local TDR patterns among sub-populations.MethodGenotyping reports were digitized from ART naïve patients followed at the Immunodeficiency Clinic at the Ottawa Hospital, between 2008 and 2010. Quality controlled, digitized sequence data were assessed for TDR using the Stanford HIV Database. Patient characteristics were analyzed according to TDR patterns. Finally, a phylogenetic tree was constructed to elucidate the observed pattern of HIV TDR.ResultsAmong the 155 clinic patients there was no statistically significantly difference in demographics as compared to the Ontario provincial HIV population. The clinic prevalence of TDR was 12.3%; however, in contrast to the data from Ontario, TDR patterns were inverted with a 21% prevalence among MSM and 5.5% among IDU. Furthermore, nearly 80% of the observed TDR was a D67N/K219Q pattern with 87% of these infections arising from a distinct phylogenetic cluster.ConclusionsLocal patterns of TDR were distinct to what had been observed provincially. Phylogenetic analysis uncovered a cluster of related infections among MSM that appeared more likely to be recent infections. Results support a paradigm of routine local TDR surveillance to identify the sub-populations under care. Furthermore, the routine application of phylogenetic analysis in the TDR surveillance context provides insights into how best to target prevention strategies; and how to correctly measure outcomes.

Highlights

HIV transmitted drug resistance (TDR) surveillance is usually conducted by sampling from a large population
The clinic prevalence of TDR was 12.3%; in contrast to the data from Ontario, TDR patterns were inverted with a 21% prevalence among men who have sex with men (MSM) and 5.5% among intravenous drug use (IDU)
Nearly 80% of the observed TDR was a D67N/K219Q pattern with 87% of these infections arising from a distinct phylogenetic cluster

Summary

Introduction

HIV transmitted drug resistance (TDR) surveillance is usually conducted by sampling from a large population. In the context of emergent HIV therapy such as occupational exposure, occult HIV DR may lead to failure of post-exposure prophylaxis [3,4] For these reasons and for the purposes of mapping the epidemic, population level surveillance of transmitted DR (TDR) remains important [5,6]; inherent in population analyses of TDR is the loss of resolution. The Ottawa Hospital Immunodeficiency Clinic routinely carries out baseline HIV DR testing [7,8,9] which provided access to the genetic sequence of the virus from the clinical HIV genotype report Using this information we re-interpreted the HIV genotype in order to determine the local TDR trends and analyzed the distribution of TDR within the sub-populations of the clinic cohort using molecular epidemiology

Methods

Results

Discussion

Conclusion