|
|
Common, Rare, and New HIV-1 Resistance Profiles Observed in Routine Clinical Practice: A Survey of over 5,000 Isolates and the Characterization of a Novel 3TC Resistance Mutational Profile Lacking 184V K. HERTOGS*1, V. DE VROEY1, C. VAN DEN EYNDE1, P. DEHERTOGH1, A. VANBLOOR2, V. MILLER3, T. ALCORN4, B. LARDER2, and S. CAUWENBERGE1. 1VIRCO, Mechelen, Belgium; 2VIRCO, Cambridge, UK; 3J. W. Goethe Univ., Frankfurt, Germany; and 4LabCorp, Raleigh, NC We present an analysis of over 5,000 samples from US and European routine clinical practice, tested last year, CLIA-approved phenotypic and/or genotypic methods (Antivirogram™, VircoGEN™). 85% of the samples analysed had phenotypic resistance to at least one antiretroviral class (NRTI, NNRTI or PI). Combined resistance to drugs from 2 or 3 classes was seen respectively in 20% and 70% of samples with any phenotypic resistance. Class-specific MDR was detected in 5%, 48% and 57% of the NRTI-, NNRTI- or PI-resistant isolates. The following overall frequencies were observed for common mutations in RT: 215Y (33%) (vs 215F (8%) or 215D/C (1.4%)), 184V (38%), 103N (20%) and 181C (14%). The following overall frequencies were observed for common protease mutations: 30N (6%), 48V (4%), 82A (14%) (vs 82S/F/T (3%)) and 90M (33%). In RT, a 151M mutation was seen in 1.5% of the isolates. Ten types of amino acid insertions were identified in the codon 68 to 70 region of RT. Several novel amino acid substitutions were identified at different RT codons (e.g., 101, 103, 181, 184), or in the protease (e.g., 88 and amino acid insertions). Interestingly, was the novel mutational pattern associated with phenotypic 3TC resistance. We observed significant numbers of phenotypically 3TC resistant clinical samples that lacked a 184V mutation, suggesting that 184V did not account for all 3TC resistance. These samples revealed common genotypic patterns including AZT resistance mutations (typically, 41L, 67N, 210W, and 215Y) plus novel polymorphisms E44D and/or V118I. These conferred 5-15 fold resistance to 3TC and did not restore AZT sensitivity. No sensitivity changes were seen with 44D and/or 118I in an otherwise wild-type background. It is anticipated that the use of phenotypic and genotypic resistance testing technologies in routine clinical practice will provide further insights into the prevalence of common and rare resistance profiles and the emergence of new resistance pathways and will assist in the individualisation of HIV disease. Key Words: Resistance testing, New mutations, Phenotype - Genotype |
|
© 7th
Conference on Retroviruses and Opportunistic Infections, |