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

IMPACT OF NEWLY HIV DIAGNOSED INDIVIDUALS ON THE TRANSMISSION OF DRUG RESISTANCE

Antivir Ther 2009; 14 Suppl 1:A40 (abstract no. 38)

S Yerly¹, T Junier², A Gayet-Ageron³, E Boffi E Amari³, V von Wyl⁴, HF Günthard⁴, B Hirschel³, T Klimkait⁵, E Zdobnov², L Kaiser¹ and the Swiss HIV Cohort Study
¹Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland; ²Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland; ³Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland; ⁴Division of Infectious Diseases and Hospital Epidemiology, Zurich University Hospital, Zurich, Switzerland; ⁵Basel University Hospital, Basel, Switzerland

BACKGROUND: The prevalence of transmitted drug resistance (TDR) in HIV type-1 (HIV-1) newly diagnosed individuals has significantly increased in the Geneva area, reaching 15% in 2008. Previous phylogenetic analyses have revealed high clustering (30%) between newly diagnosed individuals. In this study, we evaluated the respective impact of newly diagnosed or drug-exposed chronically infected individuals on TDR.

METHODS: A total of 637 individuals resident in Geneva with a new HIV-1 infection diagnosed between 2000 and 2008 (mandatory declarations) were analysed. Resistance mutations were reported according to the 2007 Shafer list. Sequences from 1,058 individuals with chronic infection (resistance testing database) were included. Phylogenetic analyses were performed on pol sequences using maximum likelihood method (PhyML). Phenotypic resistance and replicative capacity (RC) were assessed using the replicative system PhenoTecT (InPheno).

RESULTS: Mutations associated with resistance to at least one drug were detected in 8.5% individuals (NRTI 6.3%, NNRTI 3.5%, PI 1.9% and >1 drug class 2.4%). The phylogenetic analyses revealed that 35% of newly infected individuals (53% of those with infection <1 year) could be linked to a chain of transmission, whereas only 10% of chronically infected individuals were included in transmission clusters. Compared with newly diagnosed individuals infected with sensitive strains, those infected with resistant strains were more frequently found in clusters (32.6% versus 59.3%, respectively; P<0.0001) and were often part of transmission clusters composed only of newly diagnosed individuals. We also identified two clusters of TDR evolving over >2 years in recently infected individuals. The first was characterized by RT 69 insertion and Pr 90M, and the second by 103N and Pr 35 insertion. Within each cluster, very high homologies of pol sequences (98.7–100%) and of C2V3 sequences (96.7–100%) were found. In vitro RC (Pr/RT) was reduced to 32%/42% for the first strain and to 17%/29% for the second strain.

CONCLUSIONS: Reconstruction of the HIV transmission networks shows that newly diagnosed HIV infections are a significant source of onward transmission, particularly of resistant strains, thus suggesting an important self-fuelling mechanism for TDR. This has to be taken into account in the context of universal HIV testing and immediate antiretroviral therapy strategy to reduce transmission.

2009-06-09
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