18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

SUCCESSFUL IDENTIFICATION OF SOURCES OF TRANSMITTED DRUG-RESISTANT HIV-1 VIA A CROSS-SECTIONAL PHYLOGENETIC ANALYSIS

Antivir Ther 2009; 14 Suppl 1:A41 (abstract no. 39)

V von Wyl¹, S Yerly², J Böni³, C Shah³, P Bürgisser⁴, T Klimkait⁵, P Taffé⁴, R Kouyos⁶, B Ledergerber¹, HF Günthard¹ and the Swiss HIV Cohort Study (SHCS)
¹University Hospital Zurich, Zurich, Switzerland; ²Geneva University Hospitals, Geneva, Switzerland; ³University of Zurich, Zurich, Switzerland; ⁴University Hospital Lausanne, Lausanne, Switzerland; ⁵University of Basel, Basel, Switzerland; ⁶ETH Zurich, Zurich, Switzerland

BACKGROUND: Phylogenetic analyses can provide valuable information on transmitted drug resistance (TDR), but they often suffer from insufficient information on the population of potential transmitters. We aimed to combine sequences from a highly representative study with imputed infection dates to infer frequency of and correlates with TDR.

METHODS: Subtype B HIV pol sequences from 339 ART-naïve homo/bisexual patients (MSM) from German- speaking Switzerland with estimated infection dates between 2001 and 2004 were selected (tracking data), representing 60% of officially reported new diagnoses with homosexual risk exposure within that period and region. Of those, 104 (30%) were diagnosed within 1 year of documented seroconversion (recent infections). TDR was identified with the 2009 WHO Surveillance list. Sequences were pooled with all remaining tests from MSM patients (n=1,691) and analyzed with phylogenetic methods (TN93+I+Gamma; neighbor-joining trees) after removal of drug-resistance-related amino acid positions. Transmission clusters were defined via bootstrap values =980/1,000. Logistic regression models were used to identify associations with the recapturing of tracked patients within clusters of ≥2 sequences or with the presence of TDR mutations.

RESULTS: Of 339 tracked patients, 150 (44%, of which 41 recently infected) were included within 83 clusters with a median size (min, max) of 3 (2, 12). TDR was observed in 28/339 (8%) sequences, of which 20 were distributed over 14/83 (17%) clusters and 8 were isolated. Possible ART-exposed sources were included in 3/14 clusters (21%) together with 3 tracked TDR sequences. Circulation of TDR strains among ≥2 ART-naïve patients was found in 6/14 (43%) clusters, involving 10 tracked sequences. Fourteen (17%) transmission chains extended beyond 2004. In adjusted regressions for age, study center, time from estimated infection to diagnosis and ethnicity, the presence of TDR was the only predictive factor for inclusion within clusters (OR 3.1 [95% CI 1.2–8.1]); no factors explaining TDR were discovered.

CONCLUSIONS: This cross-sectional analysis suggests that at least 11% of all sequences with TDR mutations or one-fifth of all TDR clusters have originated from an ART-exposed chronically infected patient. Moreover, 36% of observed TDR and 43% of TDR clusters may be attributed to onward transmission of recently infected patients.

2009-06-09
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